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 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=27675