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
years.
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
Discussion:
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
study
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
centenarians
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
centenarians
Journal of Clinical Endocrinology and Metabolism November 2993; 88(11):
5109-5115
*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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