X-Message-Number: 27675
Date: Mon, 6 Mar 2006 19:54:01 -0800 (PST)
From: Doug Skrecky <>
Subject: Centenarian Longevity Database

   This is a database examining epidemiological associations with the
 further survival of centenarians. The purpose of this database is to help
 uncover factors which may play a role in extreme human longevity. In
 developed countries about 1 in 5,000 to 10,000 reach 100 years of age.
 The term supercentenarian is used to describe those whose age is 110 or
 over. With an average remaining lifespan of about 2 years, less than 1 in
 100 centenarians ever become supercentenarians.
   A few caveats are in order. Since no intervention trials have ever been
 conducted on centenarians, the only longevity data for this group is in
 the form of epidemiological evidence. This type of evidence can not
 provide proof of causality, but only of association. These studies all
 feature small numbers of centenarians, and so there exists a substantial
 possibility of chance associations with longevity.
   In the studies listed below from which survival statistics could be
 extracted, "No." refers to the number of centenarians in the study group,
 "Ave" refers to the average survival, "Max" refers to the maximum
 survival, and "Left" refers to the percent of subjects leftover after the
 study was terminated.

                                          Survival years
 Condition                     Country  No. Ave   Max Left  Reference
 apolipoprotein E e2/3 allele  Finland   23  4 (e)             #3
 apolipoprotein E e3/3 allele  Finland  124  1 (e)             #3
 apolipoprotein E e3/4 allele  Finland   29  2 (e)             #3
 aspirin none                  Finland  149  1.7   5           #1
 aspirin 250 mg                Finland   30  2.4   5+  13%     #1
 diet favouring beverages      Japan     10  1     5           #2
 diet favouring cereals        Japan     35  2     6           #2
 diet favouring dairy products Japan     26  3     7+  30%     #2
 diet favouring vegetables     Japan     33  2     6           #2
 illness: absence              Japan     59  3     6+ (error)  #2
 illness: presence             Japan     45  1     7+  15%     #2
 maximum age at death 1860s    Sweden              1           #4
 maximum age at death 1990s    Sweden              8           #4
 maximum age at death 1950s    World              10           #5
 maximum age at death 1960s    World              11           #5
 maximum age at death 1970s    World              12           #5
 maximum age at death 1980s    World              14           #5
 maximum age at death 1990s    World              22           #5
 sex: female                   Japan     75  2     7+  25%     #2
 sex: male                     Japan     29  2     6           #2

 (e): estimated
 (error): presumed error in Figure 3 - survival data listed only to 6

 Condition                     Country No. Hazard ratio
 C-reactive protein            Denmark 126    1.26   (ns)      #6
 interleukin-6                 Denmark 126    1.08   (ns)      #6
 interleukin-8                 Denmark 126    1.12   (ns)      #6
 tumor necrosis factor alpha   Denmark 126    1.34   (per SD)  #6
 23 variables                  Italy   110    -      (ni)      #7

 (ns): nonsignificant
 (per SD): per standard deviation
 (ni): not informative - no explicit survival statistics or hazard ratios

   In the Finnish study, the apolipoprotein E e2/3 allele was associated
 with increased longevity. This allele has also been associated with a
 decreased risk of cognitive decline in those over 75 years of age. *8
   In the above Danish study, it was found that plasma tumor necrosis
 factor alpha (TNF-a) was the only proinflamatory cytokine with a
 significant association with increased mortality. In a multivariate
 analysis which adjusted for TNF-a, C-reactive protein lost its
 association with mortality. However only a hazard ratio was computed for
 TNF-a, so unlike other studies, explicit survival statistics could not be
 extracted from this paper.
   This strong association of TNF-a with mortality may explain the benefit
 of aspirin, since aspirin lowers TNF-a.
   In a study of 104 Italians over the age of 98 years, it was found that
 99 of these had undetectable serum 25-hydroxyvitamin D. #9 Since vitamin
 D can lower TNF-a, a longevity benefit of dairy intake, as a source of
 vitamin D could thus be expected. In the Japanese study, a high intake of
 dairy products was indeed found to be manditory for a prolonged survival
 beyond 6 years. However, in Japan, dairy products are not fortified with
 vitamin D.
   In looking for alternative explanations for the prolongevity effect of
 dairy products in Japanese centenarians, the high protein content of
 dairy products might bear some scrutiny. A protein deficiency appears to
 be a common characteristic of the elderly in general. A protein
 supplement given to those over 65 years of age, resulted in significant
 increases in the ability to walk, muscular strength, as well as
 myocardial function. *10 However, when the protein intake of centenarians
 favouring dairy products was examined, it was found to be slightly lower
 than in those favouring vegetables, or beverages.
   Centenarians with lower serum IGF-1 have a higher prevalence of
 dementia. *11 Since dementia has been associated with increased mortality
 in other populations, one could expect a link between dietary IGF-1 and
 reduced mortality. It just so happens that dairy products are the single
 largest source of dietary IGF-1. This might explain the prolongevity
 effect of dairy products in Japanese centenarians.
   On a speculative note, when a powerful inhibitor of the effects of
 TNF-a, called resveratrol was given to fish, significant life extension
 is noted (below). *12

       Resveratrol dosage              Increase in survival
 per kilogram larva  per 2000 calories   median  maximum
     24 mg             53 mg (e)           0        0
    120 mg            264 mg (e)          33%      27%
    600 mg           1319 mg (e)          56%      59%

 #1 The effect of low-dose aspirin intake on survival in the Finnish
 centenarians cohort
 JAGS November 2001; 49(11): 1578-1580

 #2 Dietary patterns and further survival in Japanese centenarians
 J Nutr Sci Vitaminol 2003; 49: 133-138

 #3 Longevity and E2 allele of apolipoprotein E: The Finnish Centenarians
  Journal of Gerontology 2001; 56A(2): M75-M78

 #4 Increase of maximum life-span in Sweden, 1861-1999
 Science September 29, 2000; 289: 2366-2367

 #5 Supercentenarians: slower ageing individuals or senile elderly?
 Experimental Gerontology 2001; 36: 915-930

 #6 Elevated levels of tumor necrosis factor alpha and mortality in
 American Journal of Medicine 2003; 115: 278-283

 #7 Is it possible to predict one-year survival in centenarians? A neural
 network study
 Gerontology 2005; 51: 199-205

 *8 Apolipoprotein E, cardiovascular disease and cognitive function in
 aging women
 Neurobiology of Aging 2005; 26: 475-484

 #9 Low vitamin D status, high bone turnover, and bone fractures in
 Journal of Clinical Endocrinology and Metabolism November 2993; 88(11):

 *10 Oral amino acids in elderly subjects: Effect on myocardial function
 and walking capacity
 Gerontology 2005; 51: 302-308

 *11 Serum insulin-like growth factor-1 in centenarians: Implications of
 IGF-1 as a rapid turnover protein
 Journal of Gerontology 2001; 56A(2): M79-M82

 *12 Resveratrol prolongs lifespan and retards the onset of age-related
 markers in a short-lived vertebrate
 Current Biology February 7, 2006; 16: 296-300

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