Three Studies on the Genes and Biochemistry of Human Longevity

I'll point out three recently published papers today, all of which are the fruits of the ongoing studies of long-lived people. There are a fair number of these efforts at the present time, a combination of decades-long longitudinal studies which now consist of a cohort of exceptionally old survivors, combined with new studies launched over the past decade as academic interest in the genetics of human longevity grew. As it turns out, long-lived human lineages differ from the rest of us in a number of identifiable ways - and given that it's really only been a handful of years that these sorts of study have been underway, I would imagine that many more characteristic genetic differences remain to be identified.

A genome-wide association study confirms APOE as the major gene influencing survival in long-lived individuals

We conducted a case-control genome-wide association study (GWAS) of human longevity, comparing 664,472 autosomal SNPs in 763 long-lived individuals (LLI; mean age: 99.7 years) and 1085 controls (mean age: 60.2 years) from Germany. ... Our GWAS failed to identify any additional autosomal susceptibility genes [beyond the APOE gene]. One explanation for this lack of success in our study would be that GWAS provide only limited statistical power ... A recent GWAS in Dutch LLI independently confirmed the APOE-longevity association, thus strengthening the conclusion that this locus is a very, if not the most, important genetic factor influencing longevity.

Mitochondrial Haplogroup X is associated with successful aging in the Amish

Mitochondrial lineages described by patterns of common genetic variants ("haplogroups") have been associated with increased longevity in different populations. We investigated the influence of mitochondrial haplogroups on [health in later life] in an Amish community sample. ... [Healthier old people] were more likely to carry Haplogroup X (OR = 7.56, p = 0.0015), and less likely to carry Haplogroup J (OR = 0.40, p = 0.0003). Our results [suggest] that variants in the mitochondrial genome may promote maintenance of both physical and cognitive function in older adults.

Relationship between plasma ghrelin, insulin, leptin, interleukin 6, adiponectin, testosterone and longevity in the Baltimore Longitudinal Study of Aging

Caloric restriction (CR) is the most robust and reproducible intervention for slowing aging, and maintaining health and vitality in animals. Previous studies found that CR is associated with changes in specific biomarkers in monkeys that were also associated with reduced risk of mortality in healthy men. In this study we examine the association between other potential biomarkers related to CR and extended lifespan in healthy humans. .... Based on the Baltimore Longitudinal Study of Aging, "long-lived" participants who survived to at least 90 years of age (n=41, cases) were compared with "short-lived" participants who died between 72-76 years of age (n=31, controls) in the nested case control study. Circulating levels of ghrelin, insulin, leptin, interleukin 6, adiponectin and testosterone were measured from samples collected between the ages 58 to 70 years. ... At the time of biomarkers evaluation (58-70 yrs), none of the single biomarker levels was significantly different between the two groups. However, after combining information from multiple biomarkers [the] global score differentiated the long- and short-lived participants.

While interesting, and probably the basis for what will eventually be a massive industry of drug development aimed at gently slowing down the aging process, this sort of work is still something of a sideshow. Understanding the contributions of metabolic differences to the pace of aging and resistance to frailty and degeneration will not lead to a true cure for aging. Repair and reversal of aging, the foreseeable biotechnologies that can make the old young once again, can only come from lines of research like those undertaken by the SENS Foundation.

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