ISSN 0964-5659

LONGEVITY REPORT 54

Volume 10 no 54. First published March 1996. ISSN 0964-5659.

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Our newest, best ever.... Chrissie Loveday

Lung Cancer: Was It Really the Beta-Carotene? Jack Challem

Determinants of Human Longevity Dr Leonid A. Gavrilov

Charity - a Fast Lane to Death Brenda Goodwin

Antibiotic Resistance Dr Martin Hugh-Jones

Towards Justice Brian W. Haines

A Random Tought Brian W. Haines

Dead Doctors Don't Lie John E. Tierney

Tomatoes & Strawberries Prevent Cancer Douglas Skrecky

Sucrose Polyester Douglas Skrecky

CT-2584, a Kinder Cancer drug Yvan Bozzonetti

Life Extension with Toxic Products? Yvan Bozzonetti

Relativistic Thermodynamics From Intermediate Nanomachines. Yvan Bozzonetti

Single copy rate 3.50. Subscription rates four issues of 32 pages:- 20 (15 by Banker's Order UK only). Cheques in British Pounds should be drawn on a UK bank and should be made payable to "Reeves Telecommunications Laboratories" Alternatively, dollar checks for $34 can be accepted if drawn on a U.S. bank and made payable to "J. de Rivaz". Contents are provided for information only, under the right to free speech. Opinions are the authors' own. No professional advice is intended. If you wish others to be legally responsible for your health, life or finances, then please consult a professional regulated according to the laws of your country.

Our newest, best ever....



by Chrissie Loveday



Why does everything always have to be the newest and best? I've been quite satisfied with the oldfor ages, otherwise I wouldn't have gone on buying it! Whatever the product, the company knows it has to replace it frequently, to keep with competitors or attract a new market. It may sound negative of me, but looking at the barrage of advertising hitting us daily, I think how often the advert puts me off buying goods. After a particularly long, prime-time new advert for some car, we considered whether it would actually influence our decision to buy it. I said I was bored with it after three viewings and certainly wouldn't. John said he liked the music! It must have cost a small fortune to make it and another to screen it and here are two possible(?) customers being totally negative.



The claims put forward by teams of marketing executives are always designed to attract but all markets are extremely difficult to penetrate. UK estate agents have been prevented, by law, from making exaggerated claims for the properties on their books. They can no longer describe a dilapidated broom cupboard as a compact, delightful property in need of some renovation or amust for the D.I.Y. fan. I'm still not convinced! So it's now time for auto-suggestion. If you drink a certain product, you will instantly become one of the beautiful people who have fun, fun, fun. If you use a certain washing powder, the entire world will know what a caring person you are, to look after the family so well. If you cook someone's frozen chicken, life will be an instant, never ending party. Sadly, as we all know, life just isn't like that.



I am not advocating that we should all give up our fantasies. It would be extremely boring if we didn't believe success is possible, in anything we choose. (I exclude the lottery in my case as I always forget to buy tickets!) I would hardly have agreed to sign up for cryonic suspension, if I didn't have hopes (or as some might say, fantasies). It has to be case of being selective about the information you are given and making your own decision rather than believing everything is really newer or better. Whether choosing a new washing machine, a new car or selecting a can of beans, looking through the advertising hype is essential, to make your own decision about the product. Even chatting to friends for advice is flawed. What one person likes, another hates, especially true of entertainment!



Salesmen are actually trained to feed negative points about rival products and some times the negatives can make us even more determined to follow our own noses. An unfortunate experience with a product will make anyone resistant to all positive information and we shall probably never buy it again. Consumer reports themselves would never influence my decision to buy a washer of the same type that once washed my floor, rather than the clothes! Motivation for saying things is obvious ... they want to be more successful than their rivals. They try to say the rivals' claims are impossible and given a large enough audience, may succeed, if only temporarily. It is the final proof of satisfaction that is good enough. Even with something as rare as cryonics, other companies have to say how much better they are and that "rivals" cannot possibly succeed the way they can.



It all boils down to what you want to believe, I suppose. If you expect a particular result, it may be hard to believe that anything else can be true. If you are old enough, you may remember that a telegram during war time meant only one thing ... bad news. If you see an envelope from the Inland Revenue, it must mean a tax demmand. Be optimistic ... the telegram might mean Happy Birthday ... Inland Revenue might be sending you a tax rebate. That letter from a long forgotten friend or relation might not be the bad news you anicipate, just a contact to say hello.



Lung Cancer: Was It Really the Beta-Carotene?



by Jack Challem, The Nutrition Reporter



Note: This article is copyrighted 1996 by Jack Challem, The Nutrition Reporter. You may make personal copies, but you may not reproduce it in any publication or other type of media without written permission from the author (PO Box 5505, Aloha OR 97006) <Jack_Challem@ortel.org>. The article was reprinted with permission of Jack Challem, The Nutrition Reporter.



Two new studies have found that beta-carotene supplements might not protect long-term smokers against lung cancer and may slightly increase their risk of developing the disease.



But the studies also raise more questions than they answer. Researchers described the findings of the Beta Carotene and Retinol Efficacy Trial (CARET) and the Physicians Health Study at a press conference in Bethesda, Md., January 18, 1996.



Doctors in the CARET study gave 18,314 heavy smokers, former smokers, and former asbestos workers either a combination of 30 mg of beta-carotene and 25,000 IU of vitamin A or a placebo daily for four years. The researchers found that people taking the beta-carotene were 28 percent more likely to develop cancer and 17 percent more likely to die.



The numbers, though they might seem high, were described as interim and not significant statistically by lead investigator Gilbert S. Omenn, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center and the University of Washington, Seattle. He also said that the former smokers might have benefited from a 20 percent reduction in cancer risk, but that the data was too limited to draw a firm conclusion.



Barbara Valanis, Dr. PH., of Kaiser Permanente Hospital in Portland, Ore., and one of the principal investigators in the CARET study, said that the use of beta-carotene would result in six cases of lung cancer instead of five among every 1,000 smokers.



Meanwhile, the Physicians Health Study looked at 22,071 physicians who took a either 50 mg beta-carotene or aspirin every other day for 12 years. Charles Hennekens, M.D., of the Brigham and Womens Hospital and Harvard Medical School, Boston, reported that this study showed no significant evidence of benefit or of harm of beta-carotene supplementation on cancer or cardiovascular disease. The findings were consistent for all of the doctors, including the 11 percent who smoked and the 51 percent who were former smokers.



Were the press releases and press conference an impulsive rush to judgment?



It was hard for either researchers or journalists to take a critical look at the studies. Neither study was published in a medical journal or, at the time, scheduled for publication. Nor had either study been reviewed by scientific peers, a breach of scientific protocols. Furthermore, the data was not released just the conclusions, through press releases and a press conference.



And there are problems with the information that was released.



Both studies used synthetic beta-carotene, and there is a big difference between synthetic and natural beta-carotene, according to Jeffrey Blumberg, Ph.D., a leading antioxidant researcher. Blumberg, associated director of the USDA Center for Human Nutrition and Aging at Tufts University, was interviewed by The Nutrition Reporter.



Natural beta-carotene consists of a 50-50 mixture of all trans and 9-cis beta-carotene. Synthetic beta-carotene consists of just the all-trans form of the nutrient. The difference in structure could influence beta-carotene absorption and function. (Gaziano JM, American Journal of Clinical Nutrition, 1995;61:1248-52)



Neither study used mixed carotenoids, which are derived from natural sources and contain alpha-carotene, lutein, zeaxanthin, cryptoxanthin, and lycopene. These substances particularly alpha-carotene and lycopene have shown promise in cancer prevention (Levy, J, et al., Nutrition and Cancer, 1995;24:257-66).



The combination of carotenoids in natural-source supplements also resembles the way carotenoids are found in fruits and vegetables. That is important because virtually every public health official recommends diets rich in these foods, even if they don't recommend supplements.



The studies, begun years ago, were designed like single-drug-intervention studies, Blumberg added. Those types of studies are good for determining the therapeutic value of drugs after a disease process has begun. Such study designs, particularly among smokers at high risk of lung cancer, cant assess the preventive role of single nutrients.



Over the past few years, many researchers have been shifting their focus to other carotenoids found in fruits and vegetables. Blumberg believes that if the studies were planned today, they would have been designed differently, likely with multiple carotenoids or antioxidants.



Diverse carotenoids would have an additional benefit. Different antioxidants typically function at different cellular and molecular sites, and some antioxidants recycle and preserve each other (Chen H and Tappel AL, Free Radical Biology & Medicine, 1994;16:437-444).



More than 200 scientific studies have shown that antioxidants, including beta-carotene, play a major role in preventing cancer and heart disease. Well-controlled studies have fund beta-carotene to improve precancerous oral leucoplakia, common in smokers. Lets not throw the baby out with the bath water, Blumberg commented.



Because the studies data were not completely analyzed, released, or published, no one knows how many of the smokers also drank alcohol. This is a significant point because a 1994 Finnish study found that the highest risk of cancer was among people smoking and drinking.



Another uncertainty: no one calculated the risk of lung cancer among asbestos workers who also smoked. This would have been a very high risk subgroup.



The subjects in the CARET study were taking beta-carotene and 25,000 IU of vitamin A daily, a very large amount. Researchers were unable to distinguish between the effects of beta-carotene and vitamin A. According to Valanis, the researchers assumed the increased risk of cancer was related to beta-carotene because that is what the Finnish study also showed.



Smokers with high blood levels of beta-carotene at the start of the CARET and Finnish studies had a low incidence of cancer later on.



Those higher initial blood levels of beta-carotene could mean a lot of things. A high intake of beta-carotene or mixed carotenoids at the start of the study would suggest a high lifelong consumption of foods rich in beta-carotene and other nutrients is protective.



And what of the slight increase in lung cancers among people taking beta-carotene in both the CARET study and a 1994 Finnish study?



Blumberg said that major oxidative stresses, like smoking or asbestos exposure, could change the way the body uses beta-carotene.



Valanis said no one understands why beta-carotene might increase the risk of lung cancer among smokers, even slightly. She did point out, though, that vitamin A (to which beta-carotene is converted in the body) helps rid the body old cells and is involved in creating new ones. Its possible, she said, that cigarette smoke might trigger some sort of malignant conversion during cellular rejuvenation. It is just a wild guess.



Packer was more blunt. Once pre-cancer cells have formed in these individuals, the likelihood of cancer prevention by antioxidants is abrogated, he said.



The subjects in the Physicians Health Study, which found no benefit and no harm from beta-carotene, may have skewed the findings, Blumberg said. Doctors generally pay more attention to their own health and have exceptional access to health care. People who take good care of themselves are less likely to have dramatic health benefits, said Blumberg. The average non-smoking person might have had greater benefits, but there is no way to tell based on the data.



The real public health message should have been to stop smoking. Beta-carotene is not a magic pill, and I don't know of any scientist who has suggested that smokers keep smoking and take beta-carotene supplements. He does feel there's enough concern to discourage long-term heavy smokers from taking beta-carotene supplements. Supplements may not be an issue for anyone else.


The Nutrition Reporter, an independent newsletter, summarizes recent medical journal articles on vitamins, minerals, and other nutrients. For a sample issue, send $3 and a long self-addressed envelope with 55 cents postage to The Nutrition Reporter, PO Box 5505, Aloha OR 97006 USA. Sample articles and more info also at http://198.107.48.104/I/Challem. html. (That's a capital "eye" between the slashes.) By the way ... we do not sell vitamins.

John Hammell, Political Coordinator, The Life Extension Foundation, writes:



It was a grossly flawed study. The National Cancer Institute should look very closely at Caret Study (Beta Carotene and Retinol Efficacy Study) because the study provided 30 mg of beta carotene, along with 25,000 IU of vitamin A, for a total of 75,000 IU- a dose recognized as TOXIC, and with 25,000 IU not considered prudent on a daily basis. The potential for harm from vitamin A taken daily for 4 or more years, on top of heavy smoking does not question beta carotene's value, but demonstrates that co-morbidity occurs with the combination. For the low down on the crookedness of NCI, read The Cancer Industry-Unravelling the Politics by Ralph W. Moss, PhD ISBN 1-55778-075-7. We sell the book here at LEF.



Codex is an effort to discredit dietary supplements as part of the drug cartel's international effort to steal them and turn them into "nutraceuticals" so they can control their sale. The purpose of Codex is to control the world's food supply. As more and more pesticides are used on the food, as more food irradiation occurs, as our soil is more and more depleted of nutrients, the international need for people to have nutrients will increase correspondingly.



The globalists may be despicable human beings, but they aren't stupid. They want us all to be serfs on their global plantation, and they want control of the world's food supply, and over dietary supplements - which they'd like to wipe out and take over as "nutraceuticals." We need to monkey wrench Codex. We are conducting a Think Tank in California in order to determine the weakest links in the chain so as to know the most effective means of attack. We need donations for that purpose. Ron Birckhead has also been doing a lot of networking all over Europe, but we need donations to fund his work. Please make out checks to Life Extension Foundation, and send them to:



LEF Political Office, 1534 Polk St., Hollywood, FL 33020, USA.



The next Codex Committee meeting on Nutrition and Foods for Special Dietary Use will be held in Bonn in October. The US and UK will be outvoted just like last time, unless we can either get some delegates to shift, or can get the US to pull out of the WTO. The recent WTO effort to try to force the US to scuttle our Clean Air Act and to allow gasoline importers to import gas containing aromatic impurities that would contribute to air pollution is actually great, because it enables us to reach out to a broader group of people including the Greens and other environmentalists. It enables us to link the health movement with the international environmental movement, as long as we go about it carefully since there are drug cartel stooges everywhere.

John Hammell, Political Coordinator,

The Life Extension Foundation

800-333-2553, 305-929-2905, 305-929-0507 FAX

jhammell@ix.netcom.com

For Complimentary Copy Life Extension Magazine - Send Street Address to The Life Extension Foundation PO Box 229120 Hollywood FLA 33022-9120 USA



International Health Alliance (I.H.A) Now Forming to Oppose The Codex Alimentarius Commission re Restrictions on Dietary Supplements European Assistance Especially Needed - send phone/fax/street address.



Determinants of Human Longevity:

Parental Age At Reproduction and Offspring Longevity



by Leonid A.Gavrilov, Natalia S.Gavrilova, Galina N.Evdokushkina,

Yulia E.Kushnareva, Victoria G.Semyonova, Anna L.Gavrilova,

Evgeniy V.Lapshin, Natalia N.Evdokushkina

Center for Longevity Research at A.N.Belozersky Institute, Moscow State University, Moscow, Russia (electronic mail: gavrilov@ilr.rc.ac.ru) and Institute for Systems Analysis, Russian Academy of Sciences, Moscow



Introduction.



Despite great fundamental and practical importance, the mechanisms of human longevity are still unknown. In particular, it is not yet known whether the DNA damage and repair is really important for human longevity.



One of the approaches to resolve this problem is to study longevity of the children born by parents at different ages and to find out whether the age-related accumulation of the DNA damage in parental germ cells is important for the longevity of the offspring.



According to the existing knowledge parental age has many influences on the offspring. Exhaustive review of this topic could be found in the fundamental monograph by C.E.Finch38. The major maternal age-related changes in mammals are increases in fetal aneuploidy later in reproductive life: Down's syndrome (trisomy 21), Klinefelter's syndrome (XXY), Edward's syndrome (trisomy 18) and Patau's syndrome (trisomy 13). The paternal age effect is also well known: for example, the risk of achondroplasia, myositis ossificans, Apert's syndrome (acrocephalosyndactyly), and Marfan's syndrome all increases by fourfold between paternal ages of 20 and 50 years47,114.



There is however, one very important gap in the existing knowledge which this particular study is intended to fill. We need to know whether parental age at conception is really important for longevity of the main population of the so-called "normal healthy people", who do not suffer from aneuploidy and other obvious genetic conditions. In order to answer this question it is important to study life expectancy of adults (say, at age 30) as a function of parental age at reproduction. By that age the main part of the subpopulation of people suffering from genetic conditions is already eliminated because of higher infant and child mortality and thus it is possible to study long-term effects of parental age on human longevity. This study is also of practical importance since now there is a tendency to postpone the birth of the child to later ages and it is important to know whether it is safe for the health of the child and his longevity.



Materials and Methods.



This study is based on the analysis of Russian genealogical and longevity data. The choice of Russian data was made because of two reasons: first of all, the authors of this work are honorary members of the Russian Historical and Genealogical Society in Moscow and thus have unique access to Russian data. The second reason is that there is a strict tradition in Russian culture that every person should have a special so-called patronic name that is determined by the first name of father. Thanks to this specific Russian cultural tradition it is much easier to find information about the fathers of the persons under investigation.



The main sources of information for analysis were genealogical publications on Russian nobility5,11,13-19,22-26,28-37,43,45,46, 50 ,51,53-55,59,60,63-77,79-83,86-89,92,95,96,99, 100,104-113,121merchant1,2,82, 101 and priestly39,85 families, and also on the families related to some outstanding persons: Russian poet Alexander S.Pushkin4,58,88,105,110,121, Russian writers Feodor M.Dostoevsky118, Lev N.Tolstoy19,106,107,121, Vladimir V.Nabokov32, Russian scientists Mikhail V.Lomonosov61, Leonard Euler3, etc. The most numerous Russian noble families studied in this work are: Arseniev, Bagration, Barclay de Tolly, Bezborodko, Demidov, Dolgorukiy, Golenischev-Kutuzov, Gagarin, Golitsyn, Guedroitz, Kantakuzin, Kapnist, Kochubey, Kropotkin, Kugushev, Kurakin, Lieven, Lopuchin, Menshikov, Mousin-Pushkin, Obolensky, Narbut, Dukes of Oldenburg, Orlov, Osten-Saken, Paley, Paskevich, Potemkin, Radziwill, Razumovsky, Romanov, Saltykov, Sangushko, Sayan-Wittgenstein, Scherbatov, Shakhovskoy, Sheremetiev, Sviatopolk-Mirsky, Tatischev, Tolstoy, Trubetskoy, Urusov, Uvarov, Vasilchikov, Viazemsky, Vishnevetsky, Volkonsky, Vorontsov, Yourievsky, Yousupov, Zubov, etc.



Since in many genealogical publications birth dates only are indicated while death dates important for calculations of longevity are often ignored, we have also used information available in biographic dictionaries9,12,27,48,52,71,78,82,90,91, 97,117,119, encyclopedias10,41,42,56,62,70,102 and cemetery records (necropols)6-8,44,49,84,93,94, 98,103.



All these data were computerized and matched with genealogical computerized records in order to find both birth dates and death dates for each particular person. Finally biographic and genealogical information for 57,000 persons was computerized. The data were computerized in the form of relational database (in dBASE-III format) and each record included the following personal variables:



1. Surname.

2. First name.

3. Patronic name (name of the father).

4. Year of birth.

5. Month of birth.

6. Exact date of birth.

7. Year of death.

8. Month of death.

9. Exact date of death.

10. Sex.

11. Ethnicity.

12. Occupation (social status).

13. Cause of death (violent/nonviolent)

14. Place of birth.

15. Place of death.

16-31. Complete information about father (see items 1-15 above).

32-47. Complete information about mother (see items 1-15 above).



Items (1-9) are important for complete identification of each individual in a huge database. Items (4-9) are also important for calculation of the exact life span. These items are also important for adjusting longevity for seasonal variation and birth cohort effects. Items (10-15) contain very important information about confounding factors which should be taken into account in data analysis. Items (16-47) are of crucial importance since they contain information about parents and in particular could be used for calculation of the parental age at reproduction (together with information in items 4-6). In those cases where information about parents (items 16-47) is not available, the data nevertheless were computerized in abridged form (items 1-15 only). This was done in order to obtain large samples of birth cohorts and thus to use this information for adjusting longevity for birth cohort variation.



In order to have unbiased estimates of longevity the data were computerized only for extinct generations - birth cohorts of 1900 and earlier. In order to minimize the heterogeneity of population the data for those born before 1700 were not analysed. Thus, the analysis was made for those persons who were born in 1700-1900 and most of them already died by now. Also, in order to have unbiased estimates of longevity, only those data were used in analysis where time distance between birth date and the date of particular publication was more than 99 years (in order to have unbiased data for extinct generations).



The computerized data on human longevity were sorted by paternal or maternal age at reproduction and mean life span for adult (30 years and above) sons and daughters was calculated for different parental ages. The statistical analysis was made by standard methods (Student test).



Results



Data on human longevity as a function of paternal age at reproduction are presented in Table 1. The data show that the effect of father's reproductive age is sex-specific (observed for daughters only) and has a threshold nature - there is no effect before reproductive age 50 and there is a dramatic decrease in life expectancy of adult daughters born by fathers older than 50 years. Also sex differential in longevity is significantly decreased for the offspring born by old fathers (see Table 1).



Since paternal and maternal ages at reproduction are correlated (old mothers usually have old spouses too), it is important to study also the effect of maternal age on the offspring longevity. These data are presented in Table 2. The data show that for reproductive ages of mothers in the range of 20-39 years there is no effect of maternal age on the longevity of the adult children. Since reproductive life span of females is shorter than males because of earlier climax, the sample size for the children of very old mothers (more than 40 years old) is too small to make any conclusions. Further studies in his direction are important to resolve this problem.



The data presented in Table 1 and Table 2 are calculated for birth cohorts born in 18th-19th centuries. To ensure higher homogeneity of population, the effect of parental reproductive age was also studied for birth cohort born in 19th century only. The data are presented in Tables 3 and 4. In these cases there was a significant decrease in sample size and as a consequence the increase of standard error estimates for longevity data. Thus, the level of statistical significance for any observations is expected to be decreased and that is what was observed. Nevertheless, the main results are essentially the same - there is a sex-specific thershold effect of paternal reproductive age on the longevity of adult daughters while maternal age has no effect on the offspring longevity. Table 1.



Human Longevity as a Function of Father's Age at Reproduction.

Data for Birth Cohorts Born in 18-19th Centuries.

______________________________________________________________
Paternal Age at |  Mean Age at Death*       |  Sex
Differential |
Reproduction    |   Standard Error (years)  |   in Lifespan  
  |
  (years)       | Daughters     Sons        |     (years)    
  |
                |(sample size)(sample size) |                
  |
________________________________________________________________
   20-29        |  65.7  0.7 |  60.7  0.4   |     5.0  0.8   
  |
                |    (545)   |     (1,312)  |                
  |
                |            |              |                
  |
   30-39        |  65.5  0.5 |   60.5  0.3  |     5.0  0.6   
  |
                |    (985)   |     (2,473)  |                
  |
                |            |              |                
  |
   40-49        |  64.6  0.8 |   60.2  0.4  |     4.4  0.9   
  |
                |    (493)   |     (1,344)  |                
  |
                |            |              |                
  |
   50-59        |  60.8  1.5 |   59.4  0.8  |     1.4  1.7   
  |
                |    (149)   |      (357)   |                
  |
_____________________________________________________________________

   * Lifespan is calculated for adults (those who survived
by age
30).
_____________________________________________________________________

Table 2.

Human Longevity as a Function of Mother's Age at
Reproduction.
Data for Birth Cohorts Born in 18-19th Centuries.
_____________________________________________________________________
Maternal Age at |  Mean Age at Death*       |  Sex
Differential |
Reproduction    |   Standard Error (years)  |    in Lifespan 
  |
  (years)       | Daughters       Sons      |     (years)    
  |
                | sample size) sample size) |                
  |
_____________________________________________________________________

   20-24        |  65.5  0.8  |  60.6  0.6  |    4.9   1.0   
  |
                |    (453)    |    (723)    |                
  |
                |             |             |                
  |
   25-29        |  66.8  0.8  |  61.1  0.6  |    5.7   1.0   
  |
                |    (463)    |    (765)    |                
  |
                |             |             |                
  |
   30-34        |  65.5  0.9  | 60.3  0.7   |    5.2   1.1   
  |
                |    (331)    |    (522)    |                
  |
                |             |             |                
  |
   35-39        |  65.2  1.3  | 60.5  0.9   |    4.7   1.6   
  |
                |    (176)    |    (273)    |                
  |
_____________________________________________________________________

  * Lifespan is calculated for adults (those who survived by
age 30).
_____________________________________________________________________

Table 3.

Human Longevity as a Function of Father's Age at
Reproduction.
Data for Birth Cohorts Born in 19th Century.
_____________________________________________________________________
Paternal Age at |     Mean Age at Death*    |  Sex
Differential |
Reproduction    |   Standard Error (years)  |    in Lifespan 
  |
  (years)       | Daughters       Sons      |     (years)    
  |
                |(sample size)(sample size) |                
  |
_____________________________________________________________________

   20-29        |  66.9  0.9  |   60.4  0.5 |    6.5   1.0   
  |
                |    (395)    |    (871)    |                
  |
                |             |             |                
  |
   30-39        |  67.0  0.6  | 60.3  0.4   |    6.7   0.7   
  |
                |    (734)    |     (1,714) |                
  |
                |             |             |                
  |
   40-49        |  65.8  0.9  |   59.7  0.5 |    6.1   1.0   
  |
                |    (493)    |   (1,344)   |                
  |
                |             |             |                
  |
   50-59        |  62.9  1.5  |   59.4  1.0 |    3.5   2.0   
  |
                |    (102)    |    (229)    |                
  |
_____________________________________________________________________
  * Lifespan is calculated for adults (those who survived by
age 30).
_____________________________________________________________________

Table 4.

Human Longevity as a Function of Mother's Age at
Reproduction.
Data for Birth Cohorts Born in 19th Century.
_____________________________________________________________________
Maternal Age at |   Mean Age at Death*      |  Sex
Differential |
Reproduction    |   Standard Error (years)  |    in Lifespan 
  |
  (years)       | Daughters       Sons      |     (years)    
  |
                |(sample size)(sample size) |                
  |
__________________________________________________________________
   20-24        |  66.5  0.8  | 60.7  0.7   |     5.8  1.1   
  |
                |    (352)    |    (520)    |                
  |
                |             |             |                
  |
   25-29        |  68.7  0.9  | 60.9  0.6   |     7.8  1.1   
  |
                |    (353)    |    (562)    |                
  |
                |             |             |                
  |
   30-34        |  67.0  1.1  | 59.3  0.8   |     7.7  1.4   
  |
                |    (242)    |      (389)  |                
  |
                |             |             |                
  |
   35-39        |  67.0  1.5  | 61.4  1.1   |     5.6  1.9   
  |
                |    (122)    |    (180)    |                
  |
_____________________________________________________________________

* Lifespan is calculated for adults (those who survived by
age 30).

Discussion



Two specific effects are observed in this study. First of all, the effect of parental reproductive age on longevity of adult children is observed for fathers only (specific paternal effect). Second specific effect is that paternal age is detrimental for longevity of the daughters only(specific sex-linked effect on daughters). Both observations may have fundamental explanations in modern biology.





First of all, it is well established now that mutation rate in human males is much higher than in females20 and age of father is the main factor determining the human spontaneous mutation rate20. Thus, there is every reason to expect the effect of paternal age rather than maternal age on the offspring longevity since mutational load in germ cells is mainly of paternal origin. The reason for specific paternal effect is that mutation rate is in great extent determined by the number of cell divisions and DNA replications when mistakes are introduced. Since the number of cell divisions between zygote and sperm (in males) is much larger than between zygote and egg (in females), much higher accumulation of DNA damage in paternal germ cells should be expected. In human specis the estimated number of cell divisions in females between zygote and egg is 24, largely independent of age. In males the number of cell divisions between zygote and sperm is much larger. The number of divisions prior to a sperm produced at puberty at age 13 years is estimated at 36, and thereafter the number increases by 23 divisions per each year115,116. Thus, at age 20 the number of cell divisions is about 200 and has increased to about 890 cell divisions by age 50! Thus, there is every reason to expect specific paternal effect on mutational load and longevity in the offspring.



The second observation is that high paternal reproductive age is detrimental for daughters only. Since paternal X chromosome is specifically inherited by daughters rather than sons, this observation might indicate that critical genes (critical targets for mutational damage) important for longevity are located in X chromosome. It is important to note that there is a good reason to hide critical important genes namely in X chromosome since it is the most safe place in human genome. The reason for that is that the level of DNA damage in particular chromosome is determined by its exposure to male environment. For example, the most unfavourable situation is observed for Y chromosome that is male-specific. Since the Y chromosome is always in males while an autosome is in males only half of the time, the level of DNA damage for this chromosome should be especially high. Indeed, it turned out that the primate evolution rates (that are correlated to mutation rates) of the Y linked argininosuccinate synthetase pseudogene is about 2 times higher than that of its autosomal counterpart57. Thus, Y chromosome is the most dangerous place in human genome and that might be the reason why so few genes are associated with that chromosome. Contrary to Y chromosome, X chromosome is less exposed to male environment since females have 2 copies of it while males have only one copy. Thus, only 1/3 of the X chromosomes are in males, so the X chromosome should have mutation rates 2/3 compared to autosomes. Indeed, it turned out that the X/autosome ratio for silent changes in DNA during primate evolution (that is proportional to mutation rates) is 0.69 [57]. Thus, X chromosome is the most safe and conservative place in human genome indeed and there is every reason to hide all critical genes in this particular chromosome. One of such critical genes located in human X chromosome is gene for DNA polymerase alpha, enzyme envolved in DNA replication120. Mutations of this critical enzyme might cause decrease in the accuracy of DNA replication and may result in catastrophic increase in mutation rates. Other critical genes, located in X chromosome are genes for glucose-6-phosphate dehydrogenase (important for protection against oxidative damage of DNA and other structures) and plasma membrane Ca++ transporting ATPase. Thus, the observed specific effect of paternal age on daughters longevity might have a fundamental explanation in human biology.



It is also worth discussing the threshold nature of the effect of paternal age on daughters' longevity - virtually no effect before age 50 and dramatic decrease in longevity after that age. This observation is in accord with previous observations that the dependence between paternal age and mutation rates is nonlinear with great acceleration at old ages20. One of the possible explanations for this phenomenon is competition among sperm cells. Since only one of huge number of sperm cells succeeds in the fertilization in each particular case, damaged sperm cells with high mutational load may not withstand this strong competition. Only at very old ages when the proportion of damaged sperm cells becomes higher than some threshold level, the selection mechanism finally fails and accumulation of mutational load becomes evident.



Another interesting observation is that sex differences in human longevity are the function of paternal age at reproduction. The data presented in Tables 1 and 3 show that females live longer than males when fathers are young, while in the case of old fathers sex differences are very small and statistically insignificant. This important observation may also have fundamental explanation in human biology. Since females have two X chromosomes, they are genetically more redundant than males who have only one X chromosome. But when the father is very old and his X chromosome transfered to the daughter is full of mutational load, there is no longer difference in genetic redundancy between males and females since both have only one intact X chromosome. Thus, there is every reason to expect that with increase of paternal reproductive age the sex differences in offspring longevity should decrease.



In addition to the proposed fundamental biological explanations some other cultural and social explanations could be discussed. One of the promising approaches to discriminate between biological and social explanations is to study the effect of reproductive age of grandfathers on mother's side on the longevity of grandchildren. Since grandfather's X chromosome is inherited through mother's side only, one should expect specific effect of reproductive age of grandfather on mother's side. If this is observed, all other social and cultural explanations of the observed regularities could be excluded. Thus, further studies in this direction are extremely important as well as further support of such a studies.



Acknowledgements.



This research was made possible in part by INTAS grant #93-1617. We would also like to acknowledge support from Mr.Michael R.Geisen, OneLife International Inc. and Mr.Whit Garberson, Newton, MA, U.S.A. In order to continue this research we need now additional funding from any organization or private person. Please contact us for this purpose at e-mail: gavrilov@ilr.rc.ac.ru.



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Letter from Dr Gavrilov:

Now I am looking for a sponsor who could provide with very small urgent support for our longevity studies in exchange of mentioning the sponsor in the acknowledgements of my paper.



More specifically, I would like to provide a computer for one of the key co-authors of our paper, Dr.Yulia E.Kushnareva, Ph.D.who is working now for our joint longevity project in USA:



Dr.Yulia E.Kushnareva, Ph.D.

3 Dalecrest Ct. , Apt.102

Timonium MD 21093, USA

Tel.: +(1)-(410)-560-7167



You can find her CV and photo, reproduced here, at:

http://www.aeiveos.com/au/gavrilov-la/yula_cv.html

or http://alpha.genebee.msu.su/au/gavrilov-la/yula_cv.html



She is really an outstanding scientist and the most wonderful lady in the world I have ever seen. Moreover, she will have her birthday very soon in April and it would be nice to support her studies now.



I wonder whether it is possible to give a recommendation to Life Extension Foundation (or other potential sponsor) to support this longevity project in such a graceful way ?



Here is the text from the www page:



Kushnareva Yulia Efimovna - Research Scientist and the Most Wonderful

Lady in the World



Curriculum Vitae



Kushnareva Yulia Efimovna



Name in full: Kushnareva Yulia Efimovna



Work Address: Department of Bioenergetics, A.N.Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899 Russia

Phone: 7-(095)-9395360



FAX: 7-(095)-9393181



Data of Birth: April, 1, 1965



Place of Birth: Kishinev, Moldova



Citizenship: Moldova



Research Interest: Mechanisms of longevity and the role of mitochondria in aging process.



Education:



1982-1987 Department of Biophysics, Biology Faculty, Moscow State University



1987-1990 Graduate Student in Department of Biophysics, Biology Faculty, Moscow State University



December 17, 1990 PhD in Biophysics, (Biology Faculty, Moscow State University)



Dissertation: Regulation of ion permeability of mitochondria under conditions of free-radical reactions.



Professional experience:



1991-present Research Scientist in the Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University



1987-1990 Graduate Student in Department of Biophysics, Biology Faculty, Moscow State University and Visiting Researcher in Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University.



Awards:



Principal Investigator for the Grant from the International Science Foundation (ISF) #MDR000 (1994-95)



Grant from the Russian Foundation for Fundamental Research (1995) Grant #1-328 "Membrane Bioenergetics", Program "Engineering Enzymology" (1995)



Publications:



1. Human Longevity: Past, Present and Future. Longevity Report (ISSN 0964-5659), 1995, V.7, N 52.

2. Effects of the membrane potential upon the Ca - and cumene hydroperoxide-induced permeabilization of the inner mitochondrial membrane. FEBS Letters, 1991, 295, 77-80.

3. Mechanism accounting for the induction of nonspecific permeability of the inner mitochondrial membrane by hydroperoxides. Biochimica et Biophysica Acta, 1991, 1058, p.242-248.

4. Effect of cyclosporin A and oligomycin on nonspecific permeability of the inner mitochondrial membrane. FEBS Letters, 1990, 270, 108-110.

5. Effect of ADP/ATP antiporter conformational state on the suppression of the nonspecific permeability of the inner mitochondrial membrane by cyclosporin A. FEBS Letters, 1990, 277, 123-126.

6. ATP-syntase complex: the mechanism of control of ion fluxes induced by cumene hydroperoxide in mitochondria. FEBS Letters, 1989, 247, 255-258.

7. Ca -loading modulates potencies of cyclosporin A, Mg and ADP to recouple permeabilized rat liver mitochondria. Biochemistry and Molecular Biology International, 1994, V.34, p. 367-373.

8. The effect of cyclosporine A and oligomycin on the permeability of the mitochondrial inner membrane. Biokhimia, 1991, 56, 529-535.

9. The role of the ADP/ATP antiporter in the inhibition of nonspecific permeability of the inner mitochondrial membrane by cyclosporine A. Biokhimia, 1991, 56, 536-541.

10. Cumene hydroperoxide changes the conductivity of mitochondrial membrane for K . Biokhimia, 1991, 54, 206-212.

11. Transmembrane potential regulates nonspecific permeability of inner mitochondrial membrane. Biologicheskie membrani, 1989, 6, 1053-1061.

12. A mechanism for induction of nonspecific permeability of the inner mitochondrial membrane by hydroperoxides. Biologicheskie membrani, 1990, 7, 945-955.

13. ATP-syntase control of ion fluxes induced by hydroperoxides. X Symp.Biochem. Soc. USSR-GDR "Mechanisms of cell activity regulation". Moscow, 1989, p.122 (poster).

14. The low concentrations of cyclosporin A reseal the permeability transition pore of the inner mitochondrial membrane in absence of additional effectors. Biochimia, 1995 (in press).

Charity - a Fast Lane to Death



by Brenda Goodwin



For many of us, hardly a week passes without the aggressive rattling of collecting tins under our noses as we walk down the street. Then, along with every festive season, we receive an hysterical battering of charity appeals in the mail: deluges of emotional, guilt-inducing brochures soliciting - some even demanding - contributions. On top of all this, the Queen's last Christmas Day message, obviously designed to divert attention from her family problems, gave a heavy endorsement of altruism.



During the past 2000 years, altruism and sacrifice have been deliberately developed and promoted by the leaders of most cultures of the world. Today, altruism is a deeply entrenched part of our culture; its power and influence pervades all aspects of human life, at all levels, and most people remain unaware of the implications and totally duped by it.



There are crucial reasons why readers of this newsletter should not be duped, and the purpose of this article is therefore to point out the implications and try to explain the well-documented and increasingly accepted Neo Tech philosophy on this subject.



Neo Tech has been around for three decades, developing its philosophic system, and despite intense U.S. Government opposition, disseminating its huge body of brilliantly-researched literature around the world. Neo Tech has a good deal to say about the corrosive, and ultimately life-destroying nature of altruism.



Neo Tech has explicitly identified two groups of people in the world - the producers and the non-producers. The producers are those who create needed values for themselves and society, thus supporting their own and their families' lives. The latter group, the non-producers, are shown to be parasites who live off values earned and created by the producers.



This parasite culture was initiated and developed through the use of false guilt as a tool to undermine the income and assets earned by productive people. It is nothing new. The origins of the situation have been identified nearly 3,000 years ago, and it was deliberately and ruthlessly built up by the early Christian leaders who learned how to foist guilt on to the productive members of their society to deprive them of their prosperity and resources. Those early Christian leaders developed cunning Platonistic systems based on altruism, collectivism and egalitarianism, and were so successful in their exploitation that from that time on, religious, political and social leaders - pretty well all "authorities" - have vigorously pressed altruism on entire populations, interpreting it as a moral ethical system. It perhaps reached its horrific but logical zenith in Nazism, under the influence of the philosophers Kant and Hegel.



The principle involves the sacrifice of self, money, goods, time or any other resource, to anyone, or for the sake of anything; this is the principle on which all current political and religious systems depend, likewise charities which, with government support, have become the most ruthless exploiters of the public, these days utilising all the most sophisticated modern marketing techniques. Countless thousands of people are now involved in charity activities of one kind or another. According to a publication issued by the Charity Commission (January 1994), there are some 170,000 registered charities in England and Wales. All have paid and/or unpaid workers, thus multiplying this quoted figure many times, and everyone "employed" in such activities is living off, or deriving benefits from, the resources of others, which is parasitism. Countless thousands more, whether willingly or not, are supplying money and goods.



It needs to be well understood that altruism is a morality based on the philosophical premise that man lives for the sake of others - that man's life and property are available for sacrifice to "causes". From this concept, fake jobs, bogus livelihoods and spurious "causes" have mushroomed over the years, and more are being spawned daily.



It also has to be understood that sacrifice is the opposite of productivity. Productivity creates values; sacrifice destroys them, is contrary to human biological nature, and denies the sovereignty of the individual.



Altruism is anti-individual, and an anti-life philosophy.



"Careers" such as politics, religion and charity are by nature anti-productive, and depend on gulling the public to extract money, respect and power.



There are two main groups of the beneficiaries of the values extracted. Firstly, there are the professional advocates of altruism who function by manipulating or coercing the producer to sacrifice his time, property and earnings to themselves and their non-productive clientele. These professionals are always, directly or indirectly, recipients of the sacrifices they promote, whether it's goods, glory, recognition, self-satisfaction, an identity, or whatever. Their ongoing success rests upon the creation of an illusion that they are compassionate benefactors of the disadvantaged. The real truth of the matter is that through their dishonest manipulation they are relentlessly diminishing and destroying human values. Furthermore, much of their identity and power rests upon their influence and teaching role, encouraging the parasitical way of life in others, to ensure the continuation of their own "careers" and identities. When did you ever see a charity pack up because it had solved the problems for which it was created? Quite the reverse; the problems have hugely expanded, more have been created, and no solutions have been found. No solutions will be found because there is too much self-interest involved.



The Royal Family have long been amongst the principal advocates of charity. Their involvement goes back centuries, but was notably stepped up following the French Revolution which caused considerable unease in high places in Britain and there was a real fear that such ideas and events would spread across the Channel. Royal self-interest has continued to prevail throughout many social changes and attitudes toward the Monarchy. The underlying fact remains that being visible in charity involvement bolsters Royalty's precarious position, and is an effective way of encouraging deference from a wide range of the "lower orders".



The second group of beneficiaries is the passive recipient group - the many thousands of people who have learned to look to others for solutions to their own problems and responsibilities; who choose to live by avoiding competitive effort, and specifically design their lives to live off the State - which means the taxpayers - and any charity which can offer them something. To such people, work has become a distant, rather undesirable option, because there are so many advantages to being "disadvantaged". Succeeding generations of young people have by this time learned to prefer official poverty, with its relative security, to exerting the effort needed to earn a living, to save, and plan for a better future.



Dickens, strangely muddled in his socialism, said: "Life is given to us solely on the condition that we boldly defend it to the last." This individual, assertive attitude is inherent in all human beings, and in practice, every person's survival and happiness, as well as every facet of his or her physical, mental and psychological well-being, depends on productivity, challenge, competition, and the earning of a living. When a person opts out, choosing not to produce, or find solutions to problems, he or she inevitably becomes parasitically dependent on the producers to survive through persuasion, emotional manipulation, coercion or theft. This is an unnatural denial of basic human instincts and attitudes, a gross repression of that inherent bold defence.



To further establish their position, professional non-producers try to promote the false notion that human needs are human rights - as has been blatantly illustrated by the high-profile billboard tactics of Christian Aid. Such mystical organisations promote the scam that emotionally forcing the value producer to fill their parasitical needs is "compassion". What happens in reality is that when an honest productive person practises such altruistic sacrifice, he does it at the expense of his own productivity, while reducing his own uniquely individual value to others and society. It is only free, unsacrificed individuals who can produce to maximum quality and effect.



In a society which has been so grossly sabotaged by this destructive altruistic philosophy, it is inevitable that there should be numerous distortions and aberrations. Many large companies and corporations have, for reasons of their own, established a charity commitment, leading charities to the assumption that all businesses, even the smallest start-ups, are fair prey for their leeching and manipulation. Certain large charities maintain a trading operation, yet while pretending to be businesses, continue to expect a free ride when selling goods at commercial fairs. "We are not allowed to pay for anything," an OXFAM representative was heard to remark at one such fair. They were, in fact, being subsidised by the small dealers there, who then had to watch while the charity undercut their prices - they could because they were selling donated goods - and ruthlessly enticed and poached customers that the dealers had won through years of advertising and ongoing hard work. On the other side of the coin, some businesses, when experiencing a cashflow problem, appeal to their customers for donations instead of utilising the normal channels for raising extra funds. All such instances of exploitation or begging are aberrations, and evidence of choosing the parasite route instead of engaging in competitive market dynamics.



The "teach a man to fish" concept has often been aired in defence of some charity work, but has made little real headway. In Britain we have overwhelming evidence that a huge segment of the population simply doesn't want to know about "learning to fish." Between the welfare state and the charities, what unproductive people have learned is that they can get something for nothing, so now they expect the fish to be handed to them on a plate. Fried for them too, of course. By contrast, those who want to learn and become productive do so through their own motivation; "where there's a will, there's a way." It has been amply shown that so-called "disadvantaged" people who want to create a successful, independent life can do so.



Most non-productive people, whether active professionals or their recipients, are undeveloped, immature people who have chosen to stop their learning and growth early in life. Many have stopped in childhood. Having learned to read and do arithmetic - and some don't even get that far - they consciously stop exerting effort, and then they stop growing.



Growth death occurs when a person chooses to avoid the integrated thought and rational effort required to produce competitive values. Such a non-producer's life then begins to move inexorably along the death course. The cycle that starts with growth death inevitably goes on to emotional death, when value-based friendships and love relationships stop growing, and the person cannot experience lasting prosperity and happiness. And then the only outcome of this state is physical death.



Growth of the mind is not automatic; it requires ongoing conscious effort. When a person defaults on this effort, his or her mind stops growing. When intellectual growth stops, the capacity for happiness and pleasure begins shrinking, and the individual begins dying.



Human ageing is a process of deterioration - physical, mental and psychological. Growth is the opposite of deterioration, and the two factors cannot co-exist in the same body. But if growth stops, ageing begins.



Human life may never need to age. In the philosophy that has been handed down to us, a whole package of undesirable things has been linked to what are termed the declining years - poor health, memory loss, physical deterioration, etc, all tied to the mechanism of nature where you stop, give up, wither and die. But no scientific evidence dictates that a person has to age and die. A person may be able to live indefinitely under fully integrated, fully rational, physical, psychological, intellectual and emotional conditions. We are now living in an age when Neo Tech has pinpointed the conditions and provided the override to the death mechanism; up to now, this was never available or possible, due to the distorted philosophies that have been passed down through the centuries. In addition, many of us have now learned the crucial importance of anti-ageing nutrition; that a life extension diet with supplements can stop and actually reverse the ageing process. This is what has become known as the "new nutrition", which is worlds apart from the "healthy eating", "healthy choices", etc, advocated by governments.



But a largely unrecognised essential is individual growth. It is not automatic, but anyone can learn how to expand the value of his/her life. The key is to increasingly develop knowledge and productivity, towards goals of ever increasing earned power, prosperity and happiness. Anyone can learn how to continuously extend his/her biological/psychological life through Neo Tech knowledge, technology and business. Youth- rejuvenating immortality is the supreme achievement for conscious beings as their individual lives become ever more valuable with increasing age, knowledge and experience. Death is the ultimate cop-out.



For death is obsolete. With current technology, and despite frenzied Government attacks on life extension projects, commercial biological immortality for all conscious beings is known to be possible this decade, by several different scientifically feasible routes. It will be quickly accomplished when the current anti-life, mystical cultures are exposed for the scams that they are, and wiped out.



Governments and their parasitical soul-mates, such as the charities and churches, are all working for, and contributing to, the death process, as this is what serves their own agenda. A scientist at the Institute of Human Ageing at the University of Liverpool was recently quoted as saying: "We aim to improve the quality of life, not to extend lifespan. If we started to delay ageing as we can in rats, so that people lived to 150, there would be insupportable economic and social consequences." That just about encapsulates the attitude and policies of deathism which are followed by our "authorities". Planned obsolescence of individuals is what it's all about.



All these anti-life merchants base their entire work and programs on the death cycle and are working desperately now to maintain it. As evidence of their frantic state, one has only to recall the vicious, armed Government attacks on the property, products and personnel of companies offering a different agenda, viz. the I & O Publishing Company in Nevada (Neo Tech) and the Life Extension Foundation. In many countries, access to imported herbal products and dietary supplements has been severely restricted, and the United States is said to be stealthily establishing a multi-agency task force to block the importation of anti-ageing products.



In addition, quietly and insidiously, day in and day out, governments are building up the dependency culture, and vigorously supporting all agencies which encourage non-productive people to be increasingly dependent. It has been astutely observed that dole claimants are "ideal citizens" from the Government point of view; aside from the reasons given, the most basic must be that dependency constitutes a deeper entrenchment in growth death, which is a major step along the death cycle. Along with the dole claimants, and often synonymous with them, are of course all charity recipients.



For those of us who believe that the most precious, important value in the universe is the ongoing life and development of the individual, integrated, physical and conscious self, it is irrational and impossible to support policies and agencies promoting deathism.



Remember that the ultimate specific value is for you to continue living as an individual - to continue experiencing flesh and blood life, growth, thoughts, values, prosperity, love and happiness forever. This is possible because the development of human consciousness obsoletes nature's need for ageing and death, and far surpasses the evolutionary process in efficacy for species survival and for adapting to environmental changes.



To experience ongoing human life and growth, the primary need is to invest in yourself. You have no responsibility towards other people and their problems, only to yourself and your own dependent children who are not yet able to support their own lives and ambitions. Investing in yourself means taking responsibility for your own life, health and future; devoting your resources to whatever life extension and health products you choose, any needed products to enhance your appearance, and ongoing education and skill development for your longterm future. Why throw your valuable resources at stunted, switched-off people who have chosen not to develop themselves and to go the death route ?



We have all contributed in some degree to altruistic, growth-death concepts because they are so written into our culture and lifestyle that we tend to accept them without question. But the situation is changing; a greater understanding has developed, the tide has turned, and parasitism is being more widely recognised for what it really is.



What is needed now is for all productive people to stop altruism cold by rejecting sacrificial demands. When enough people refuse to go along with the appalling scam that has been imposed upon us, this terminal disease of sacrifice can be eradicated, and fully-flowering productive life and growth can prevail.



Brenda Goodwin is publisher of the Always Options series of Special Reports.



The Neo Tech Discovery may be obtained through Direct Link, Freepost (Ex 1078), Torquay, Devon TQ 7BR. Tel: 01803 291539. Price: 58.00.



Editorial comment: This is obviously an emotive topic, and whereas we welcome reasoned comment we prefer not to publish name-calling reposts.



The motivation to give to charity is varied. Some people think their donation to a relief charity will really make a difference and save the world, whereas others may contribute to a life extension or cryonics organisation's request because they think they may actually save their own lives. This more like paying for a service. You can also invest in life extension companies with a small chance of financial return.



Antibiotic Resistance



Collected by Martin Hugh-Jones, ProMED Acting Moderator



[1] Date: Fri, 9 Feb 1996 22:21:51 -0500 (EST)

From: John Prough <jop@terra.cnct.com>



Most people who are reading ProMED already agree that prudent use of antibiotics is wise. But as a non-health professional, I hear "regular" people say over and over again that they went to the doctor to get "something" to take for their illness. The invariable reply to someone mentioning being sick is "Are you taking something for it?"



They want an instant magic cure. There is zero awareness of the distinction between viral and bacterial. [Antibiotics are only effective against bacteria - Mod.]



If I mention this to the sick person or relative of the sick person, they nod their heads, but they don't seem to actually change their behaviour. These people don't read ProMED or Science News.



Of course, this is simply anecdotal and does not reflect any statistical significance, but my point is that the people who are aware of the problem aren't the ones who need to be aware of it.



To say nothing of the horror of the possibility of some antibiotics being made available over the counter, of which I have heard reports. They can't really be serious, can they?



[In many countries, potent antibiotics are freely available over the counter. I have also seen antibiotics sitting in the hot sun at outdoor stalls in the black market at Rangoon, Myanmar. Perhaps that reduces their potency so much that although they cannot cure diseases, at least they cannot produce resistance - Mod.]



[2] Date: Sun, 11 Feb 1996 11:36:46 +1100 (DST)

From: Derek Mitchell <derekm@lad.med.utas.edu.au>

Does anyone have any [data] on correlation between brief (<3 days) and conventional (7< 10 days) treatment lengths of antibiotics and their effect on drug resistance patterns among community acquired infections?



I am concerned with what appears to be a common practice among sufferers of clinical disease (in developed countries anyway) of ceasing their antibiotic course prematurely. The surplus may of course be discarded. In Australia, that means it is inevitably buried in landfill disposal where the environmental effects are literally placed "on hold".



However the surplus is frequently kept for a subsequent illness, shared directly, or given to another person. This behaviour increases the number of exposure episodes to the antibiotic. Whether this is significant obviously will depend on the antibiotic, due to differences in total excreted active substance, and the fate of the excreted substance.



I draw no distinction as to whether the antibiotic intervention may have been microbiologically appropriate.



--

Derek Mitchell

Derek Mitchell, family physician. <derekm@lad.med.utas.edu.au Ph: +61 02 438 000 Fax: +61 02 430 201 AH: +61 02 436 427 Snail: 34 Wellington Road, TASMANIA 7015, AUSTRALIA



[The classic case is TB in developing countries. It is common for patients to feel so much better after starting their 6-12 month course of treatment that they stop taking antibiotics. Then they relapse and have to be treated again, and again, leading to resistance.



I have also been told that in some malarious countries, people given chloroquine for prophylaxis save the medication to treat an attack of the disease; but as they don't know what the treatment regime is, they underdose, leading to resistance - Mod.]



This is re-printed from the ProMed Internet mailing list, by kind permission of Martin Hugh-Jones, ProMED Acting Moderator.



To subscribe to ProMED, send email to <Majordomo@usa.healthnet.org> with the following command in the body of your email message:

subscribe promed <your email address>

Towards Justice



by Brian W. Haines



Whatever may be the future in store for medicine and extended life there will always be a need for some method of dispute resolution. In the English tradition which includes the American system the law has traditionally taken the form of an adversarial proceeding. This has produced injustice. It cannot be proved it has produced injustice, but sufficient people are dissatisfied with the results to assume the Courts are inequitable. The reasons are clear, the best lawyers win, and not the best cases. You can buy justice, those with few resources either are barred from legal proceedings by lack of money or they suffer from the inadequacy of representation. It is a fight and the finest wins.



The argument put forward by the lawyers and politicians is this may be a poor system but it is the best we have, no one has produced a better solution to the problem of dispute resolution. But there are those who believe somehow or other there must be a way of sorting out who should pay the penalty for misbehaviour, who should pay for an accident and who should pay for the faults in the various aspects of difficulties and frictions that arise from day to day living.



Enter as they say "Solomon". "Solomon" is a computer programme. From time to time various experts contend there is a solution to all our manifest difficulties in mathematics. The world, so the theory goes, runs upon mathematical principles. There is a rhythm that can be calculated. Life itself is the result of the combinations of numerous elementary particles and so forth. What could be more logical than to believe all answers can be found in the complex set of calculations that are now possible by reason of the latest technology.



[Editorial note - since this was written it was discovered that "Solomon" was some journalist's idea of a joke. However I see no reason why it shouldn't be a reality some time, so Mr Haines' arguments are still worth considering as it could happen one day!]



If people submit to the law of a computer then it is evident the computer can solve their problem. This is as logical as the light the day. Whether this is a feasible operation depends upon two initial questions; firstly are people going to accept the solution given by the computer and secondly; has the computer sufficient material to process an adequate solution. There is a very old and truthful computer adage that is very easily over looked when computers are called in aid for any operation.- Garbage in, garbage out -. Computers are as fallible as the people who have constructed the programme and the inputs.



[Editorial note: really the law is just a computer using humans as its computational elements. The rules of evidence are a sort of computer programme.]



It is very tempting to believe there is such a thing as abstract justice: the idea that somewhere out there a form of absolute right can be found. This is wrong. Unfortunately the designers of "Solomon" the computer programme have fallen into this error. Even their own publicity material falls short of logic. It goes almost without saying that all the famous cases when fed into their computer come up with a different answer to that found by the Courts. This in itself practically condemns the programme as being inaccurate. It is logically impossible for the computer to have been programmed with all the case histories from legal literature which by definitionhave to be accurate findings, and then to claim the computer can find later cases to be wrong.Obviously the later cases should also have been programmed in as part of the data base as to the way the Courts function.



It is a chicken and egg situation. You cannot have law without legal cases with solutions, for that is the raw data from which all law literature derives. The sources of law are to be found in the legal decisions, if the legal decisions are thought to be wrong, then the elemental data is wrong.



It was thought twenty or thirty years ago that all law could be reduced to mathematical equations. The problem this theory encountered was the same one the computer has to face. Which law, and what is the underlying philosophy. Roman law, Communist law, English law and Palm tree law all have very different approaches to problems. The concept of murder for instance can be very different viewed from other legal systems. The idea of murder can also be different depending upon circumstances within a system. It is not good enough to claim there is a basic definition and anything outside it cannot be adjudged to be murder. There are many types of action which can only be seen to be murder after the whole action has been examined so that it is the end product as it were that must be judged. It also works the other way round as well.



Much is claimed for artificial intelligence. The worst aspect of this new discipline is the name. It is essentially a misnomer. It is not intelligence nor anything like it. Intelligence is totally a human attribute, it does not exist in machines. One of the most famous misconceived tests is that of a person interacting with a keyboard and being asked to judge whether a machine or a person is operating the responses. People are very easy to fool. It does not follow that because a number of people are unable to say whether they are interacting with a machine or not does mean the machine has intelligence. It merely means some-one has been able to anticipate a range of problems. It is the same as some one watching a magic show, being unable to see how a conjurer does a card trick does not mean the conjurer is a real magician.



So we return to computerised law. Who decides whether the input has been sufficient? Who decides upon a mal-function in the computer? How is case law up dated in the data base?



The case law from which the computer draws in the future would be from itself. This could be suspect law by reason of various input anomalies. Perhaps later information would show earlier decisions to have been wrong. The question is would it automatically alter the constructs within the computer programme for decision making?



At present a wide number of Courts have a variety of Judges and a variety of juries. This means there can be an inbuilt method in the system whereby poor results are automatically over ridden by other cases dealing with similar facts. A computer system will only have one decision making centre it cannot correct itself.



In the brave new world of extended life, long memories will look at the old Court system with nostalgia. It is like today when you go to the Bank. There are endless mistakes because the Computer is always right, the individual is always wrong. Many are looking with longing at the places where Computers do not intrude, where personal service gave instant answers.



The Computer is not a universal panacea for the manifest failings of mankind. It is not a substitute for a bad political or legal system. There is no point at all in replacing a Court system which works some injustice with a mechanical system that will work even more injustice. The common sense approach is to get the present legal systems working properly and then replace the parts that can be computerised with a Computer; nothing else makes any sense at all, it is a case of the blind leading the blind otherwise.



Of course things are bad, but to computerise all these mistakes is absolute madness.

A Random Thought



by Brian W. Haines



Odd isn't that France where no one cares a hang for healthy living should produce a woman of 121 years old. In Devon there are people who are touching 111, none of whom have heard of oxidising agents. Yet the U.S.A. which worships health and youth and spends a fortune on every crank theory can hardly raise a few active centenarians.




Dead Doctors Don't Lie

This is the title of an entertaining and informative cassette concerning the medical profession as seen form the eyes of a practising vetinary surgeon, Joel D. Wallach, DVM,ND,MS,MD.



Its sub-title is Learn why the average life-span of an M.D. is 58 years.



It may be obtained from John E. Tierney 18163, W. Twin Lakes Boulevard Wildwood Illinois 60030 USA



It is free in the USA, if sending from overseas some IRCs to the value of $2.60 would be appreciated for postage.



It was originally intended to promote a vitamin sales project, but there is no hard sell from Mr Teirney and in fact no details of the project were enclosed, just a verbal message on the cassette to telephone if you are interested.

Tomatoes & Strawberries Prevent Cancer



by Douglas Skrecky



What would be the optimal anticancer diet? Obviously one including lots of fruits and vegetables. The hard part comes in deciding which fruits and vegetables. Recent research has helped clarify this. Of 46 fruits and vegetables only two were found to be related to reduced prostate cancer risk: tomatoes and strawberries. Broccoli turned out to be a dud, as did cantaloupe, carrots, kale, oranges, mixed vegetables, spinach, yams, etc. Surprisingly pizza turned out to be a health food due to its tomato content, with a 15% reduction in risk associated with high consumption. High tomato consumption reduced risk 26%, high tomato sauce intake 34%, while consuming a single serving (.5 cup/week) of strawberries reduced risk by 20%. The benefits of consumption of all tomato based products turned to out to be highly leveraged with respect to mortality. Most cases of prostate cancer turn out to be fairly benign, while some (called stage D) tend to be fatal. Tomato product consumption of over 10 servings per week reduced risk of prostate cancer by 35%, but reduced risk of stage D cancers by 76%. The active ingredient in tomatoes was believed to be it's red pigment lycopene since intake of tomato juice was unrelated to prostate cancer risk1. Drinking tomato juice with 1% corn oil has been found not to increase plasma lycopene levels, while drinking the same juice with corn oil that has been cooked for 1 hour greatly increased lycopene levels.2



In other research lycopene has been found to be 10 times as potent as beta carotene in inhibiting cancer cell growth in the test tube.3 This may explain why tomato consumption is beneficial, while intake of beta carotene rich foods is insufficient to be of benefit. Beta carotene supplements have been found to reduce plasma lycopene levels, which may account for why supplemental beta carotene has been suggested to increase both lung cancer and ischemic heart disease risk.4,5 [but see articles on this earlier in this issue of Longevity Report - ed]



High tomato intake reduced cancers of the oral cavity, pharynx, oesophagus by 35%, stomach cancer by 57%, colon cancer by 61% and rectum cancer by 58%.6By comparison high fruit and vegetable juice consumption had no effect on colon cancer risks, broccoli was a dud, as was Brussels sprouts, cabbage, carrots and legumes. Green leafy vegetables reduced risk slightly by 11%, high fruit intake by 14%, while cauliflower actually increased risk by 39%. Potatoes increased risk by 24%, but this may been due to other half of a basic meat & potatoes diet. Moderate garlic consumption had no effect, but high intake reduced risk by 32%.7



Of the dietary carotenoids examined only lycopene has been found to reduce cervical cancer risk. No benefit was found for lutein (greens), while results for alpha carotene, beta carotene and cryptoxanthin (oranges) were ambiguous.8



The effect of fruit and vegetable intake on cancer mortality in those over 66 years of age found some interesting correlations. Spinach and green vegetable consumption offered no benefits. High broccoli & Brussels sprouts intake reduced mortality by 20%, dried apricots, prunes and raisins reduced mortality by 40%, tomatoes by 50% and combined strawberries and melon intake by an astonishing 70%.9



The red pigment in cultivated strawberries is the anthocyanin pelargonidin-3-monoglucoside. There have been no experiments that I am aware of in vivo testing the effect of pelargonidin on tumour growth. However it is active in suppressing tumour growth in vitro. (Neoplasma 28(1): 11-18 1981) Considering that 2 epidemiological studies have implied that dietary strawberries are the most potent inhibitor of cancer in humans, then perhaps a Nobel prize is waiting for the first researcher to thoroughly investigate the effect of strawberries on in vivo tumour growth.



What can we conclude from all this? It is time to start gobbling down lots of tomatoes and strawberries!



1 Intake of Carotenoids and Retinol in Relation to Risk of Prostate Cancer1767-76 Vol.87 1995 J Natl Cancer Inst

2 Uptake of Lycopene and its Geometrical Isomers is Greater from Heat-Processed than from Unprocessed Tomato Juice in Humans 2161-2166 Vol.122 1992 J Nutr

3 Lycopene is a more Potent Inhibitor of Human Cancer Cell Proliferation than Either Alpha-Carotene or Beta-Carotene 257-266 Vol.24 1995 Nutr Cancer

4 Skin Lycopene is Destroyed Preferentially over B-Carotene During Ultraviolet Irradiation in Humans 1854-1859 Vol.125 1995 J Nutr

5 The Effect of Vitamin E abd Beta Carotene on the Incidence of Lung Cancer and other cancers in Male Smokers 1029-1035 Vol.330 1994 N Engl J Med

6 Tomatoes and Risk of Digestive-Tract Cancers 181-184 Vol.59 1994 Int J Cancer

7 Vegetables, Fruit and Colon Cancer in the Iowa Women's Health Study 1-15 Vol.139 1994 Am J Epidemiol

8 Dietary and Serum Carotenoids and Cervical Intraepithelial Neoplasia 34-38 Vol.48 1991 Int J Cancer

9 Increased Green and Yellow Vegetable Intake and Lowered Cancer Deaths in an Elderly Population 32-36 Vol.41 1985 Am J Clin Nutr






Sucrose Polyester

by Douglas Skrecky



Zero calorie fat substitutes have been touted as health enhancing. A recent report on sucrose polyester fat substitute should give cause for concern. No effect on body weight was found for feeding human subjects either control margarine or margarine doped with 50% sucrose polyester for 4 weeks. Plasma levels of cancer fighting lycopene were significantly decreased by sucrose polyester consumption. This report implies that this fat substitute will not act to reduce body weight. Conversely it will probably act to increase the risk of cancer by suppressing plasma lycopene levels. If this is so then the release of sucrose polyester for human consumption by the FDA might come to be regarded by some as a criminal act subject to prosecution at a future date.



References:



Sucrose Polyester and Plasma Carotenoid Concentrations in Healthy Subjects Am J Clin Nut1995;62:591-597



Intake of Carotenoids and Retinol in Relation to Risk of Prostate Cancer J Natl Cancer Inst1995;87:1767-1776



Tomatoes and Risk of Digestive-Tract Cancers Int. J. Cancer 1994;59:181-184



CT-2584, a Kinder Cancer drug



by Yvan Bozzonetti



CT-2584 is the code name for a product with very interesting properties for life extension. The was an article about it on the "technology" page in the 20 January issue of New Scientist p. 18.



Under the title: "Kinder" cancer drug goes on trial, there was the following information:



Around thirty patients with advanced cancer are to receive a drug produced by Cell Therapeutics Inc. from Seattle. CTI's drug, called CT-2584 targets phosphatidic acids (the fatty signalling molecules in tumour cells) and enzymes producing it. According to CTI's president, these molecules are 10-15 times more abundant in cancer cells. CT-2584 work by boosting production of these molecules until they destroy the energy factory of the cell. Starting with a lower concentration, normal cells are undisturbed by drug concentration up to 15 times as high as is required to kill cancer cells. Screen tests conducted at the National Cancer Institute in Bethesda give the same killing effect at the same dose on 65 different cancer types. The first human trial will be conduced in UK by Malcolm Ranson on behalf of the Cancer Research Campaign.



Now, some comments:



First, it is very interesting to have a low toxicity drug able to act against at least many cancers, or all of them.



Second, there is a potential use of CT 2584 not envisioned in the paper: We know an important part of the ageing process comes from the limited reproductive capability of cells. This is produced by the so called telomere reduction. Each chromosome ends with a nonsignificant stretch of DNA. DNA copying proteins stick to that part and start to copy the next generation DNA as they move along the genetic material molecule. The DNA part under the initial position is not copied and after fifty copies or so, there is no more room to fix the copying system on the DNA. The full DNA end can be regenerated by the telomerase enzymes, but few cells have it in a normal organ. This seems to be a evolutionary trait selected to limit cancer risks. If a cell looses its contact with nearby ones, it starts to reproduce to close the wound. Some times, there are nearby cells but the communication system is crippled. If there is an infinite reproductive capability, this gives a cancer. May be one cell out of 100 000 have the immortality ticket in the body. There are products able stimulate the telomerase production in any cell and so turn them into non ageing lines, but the first effect would to expand by a factor of 100 000 the cancer risk. In this case, anyone looking after a telomere regenerating drug would end with many cancers in few months.



The prospect of a nontoxic anticancer drug such CT-2584 is then particularly interesting. Even if the product don't work well on large mass of cancer cells, we know it work on isolated cancer cells, this is what would be found at start after using a telomerase stimulating drug. So, whatever the current test outcome, we know it could help for life extension.



My last comment on the subject holds in that: Is there anybody able to get CT-2584 for life extension trial?



Any comments or suggestions welcome!



Life Extension with Toxic Products?



by Yvan Bozzonetti



If a product is a toxic, it must reduce your life expectancy and so the logic goes: If a product reduces life expectancy it must be toxic...



In its book : A Guide to Anti Ageing Drugs1, Dr. Thomas Donaldson takes the case of vitamin C as a counter example of life extending product. No animal experiment has demonstrated an extended longevity in the laboratory, there is even an experiment where mean life expectancy was reduced for animals taking vitamin C. Surely, most people would conclude with T. Donaldson on the hazard of taking ascorbic acid for a long period...



Now, I turn to a disturbing experiment: Rats feed with a nonlethal dose of a toxic product live longer than well nourished rodents (information seen in a New Scientist December issue). Why? The answer shed a strange light on the value of animal experiments: Laboratory rats benefit from good food, a stable environment with few stress, have no illness and... become lazy. They overeat, weight too much and get a large life expectancy reduction from heart and coronary problems. On the other hand, a toxic product reduce appetite and produces slimmer rats with better life expectancy.



If, in this environment you test some products to see if they prolong life, you will end with a curious result: Only toxic samples will give a life extension! If you have a beneficial product, it will not cut on animal weight and will generate no life benefits. Worst: If it act on mood so that rats feel more happy they will eat more, get more weight and die sooner.



Is this the case with vitamin C ? May be... Animal experiments are often seen as more credible than any other, now we must recognize that: They are of no value if the weight parameter is not under control and properly taken into account. In particular, if a drug produces both, a weight loss and a life extension, there is a high probability we are facing a toxic product!



Until good results are produced at the animal level, the best approach remains the biochemical test at the cell culture level. That kind of cheap experiment has fewer parameters and so is less subject to unexpected side effects.








A Guide to Anti-Ageing Drugs

can be purchased from

Thomas Donaldson, PhD

80-Q N. Cabrillo Hwy, #247

Half Moon Bay,

CA 94019

U. S. A.



Longevity Books has two copies for re-sale to UK or European readers for 15 each post free.

Relativistic Thermodynamics From

Intermediate Nanomachines.



by Yvan Bozzonetti



Nanotechnology can open, it seems, a new scientific domain to the realm of technological possibilities, namely the relativistic infinite dimensional phase space of relativistic thermodynamics. That may be very interesting and allow understanding of the origin of life.



Classical ideas about nanomachines fall into two separate domains: The first is a micron level analog of macroscopic technology. It contains gears, springs, pipes and so on. Such systems are produced as an offspring of microelectronics and use the same surface etching technology on silicon. Another approach starts from simple molecules and try to build larger systems. This is more chemical or biochemical at the start. On physical grounds, the first top down technology is firmly classical, the second, on the other side is inevitably rooted in quantum mechanics.



In physics, the classical/quantum boundary has always been a problem. How to mix together a real number deterministic space with a complex probabilistic one? Because nanosystems encompass the mixing scale, there is the possibility to explore and use that domain with them.



Now it seems there is a theoretical understanding of the subject, thanks to Arlen Anderson from Imperial College London1. The information was summarized by John Maddox in the 9 February 1995 issue of Nature2. The idea goes as follows:



On the quantum side we start with a pair of conjugate variables, say the space coordinates q and impulsion p. We must have [p,q] = pq - qp = i where i is the square root of minus one.



On the classical edge, dynamics may be formulated in a number of ways: Force = mass x acceleration in Newtonian formalism, L = kinetic energy - potential energy in Lagrange, H = kinetic + potential energy for Hamilton ... The analog of the quantum bracket is the Poisson's formalism: Starting with two variables x and y, two functions are produced: F(x,y)and G(x,y). Using the partial derivative along x and y: Dx and Dy the Poisson's bracket writes down : {F,G} = { Dx F Dy G - Dy F Dx G } = 1. Anderson's deceptively simple idea is to put the two formulas end to end:[ A,B ]* = [A,B] + i{A,B} = i.



Any system is so partly quantum, partly classical with no conflict at the boundary where one part take over to dominate the other.



Now, p and q form a six dimensional nonrelativistic phase space. That space is the one used to count the number of allowed states of a system in the probabilistic form of entropy. The entropy itself is the Log of that number, the zero be taken at the absolute zero Kelvin temperature for a crystallised object. This is the so called third thermodynamics law. Now there is the background to go to nanosystems.



If we have some objects, for example a set of molecules moving on a small surface, their displacements are not fully constrained to the surface, because this one is small. There is then a mixing of two spaces: One limited to the surface and endowed with two dimensions, D2 and another with three dimensions, D3. The corresponding thermodynamic phase spaces have respectively 4 and 6 dimensions.



If the surface is relatively large at molecular scale, the four dimensional phase space will dominate and the thermodynamics will be mainly on the surface. Nevertheless, it remains a small component in three dimensions giving two extra coordinate in the entropy phase space. This added room will accommodate far more states so that the D2 entropy (or disorder) will see an endless sink : The added dimension of D3 displaces the D2 thermodynamics equilibria towards more order. That order-making process could have worked as a scaffolding on small clay crystal surfaces at the start of biochemical evolution. Life could well be the end product of that process.



On the nanotechnology side, that opens the possibility of producing at no energy cost some out of equilibria synthesis. This thermodynamic catalysor could be tailored with three parameters: the surface's form and its x, y lengths.



Now enter the quantum - classical mixing: The preceding results can be duplicated in the two domains without problem. There is nevertheless a new possibility: If the quantum space is seen with a four dimensional phase space and the classical domain with a six one, entropy will flows from quantum to classical realm : Anderson formalism provides the bridge between the two worlds.



For a quantum observer, entropy seems now to escape at infinity and disappear completely, the classical domain acts then as an infinite dimensional quantum phase space. Infinite dimensional phase space is the hallmark of relativistic thermodynamics3. Without going to speed near the one of light or giant gravitational fields, there is a door towards relativistic process at low energy. Now, from Anderson, there is no system only classical or quantum, so the classical phase space must have a quantum analog. In quantum mechanics, relativity is the signpost of the second quantification. So, the first quantum space is associated with a classical domain and that domain is associated with another quantum space, the second quantification one. The infinite entropy sink so created would build ever and ever more organized structures, this is life.



At some point in the evolution, life has lost its roots in the small surface domain, from here it has lost too its entropy sink and the order capital has thrived on a continuous input of energy. When the order get erroded in some place, the result is death. Death is, in this view, the far reaching effect of the infinite dimensional phase space lost. Can we fight ageing with the help of entropy sink nanosurfaces? The question would deserve some thought.



The next step is : What if the nanosurface is designed so that the four dimensional phase space is mainly associated with classical (Euclidean) domain ? That time, the infinite sink is the first quantum space. There is no "second Euclidean" world, so that quantum space takes simply the part of relativistic Euclidean thermodynamics. What are the prospect of ordering Euclidean space ? What technologies could follow from it? Some answer must be left to further articles.



Fine grained clays such kaolin could turn from ceramics stuff to a new high tech domain. That material is a good potential support for nanotech thermodynamic systems.



References



1 Anderson Arlen, Phys. Rev. Lett. vol. 74 p. 621-625; 1995.

2 Maddox John, Nat. Vol. 373 p. 469 1995.

3 Tolman, Richard C., Relativity Thermodynamics and Cosmology, Dover New York (1987) Repr. from Oxford Univ. Press (1934).

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