The Search For Genetic Polymorphisms of Human Longevity

Some people have better genes than other people; such is the luck of the draw. The effects of most genetic differences on human longevity appear to be small in comparison to the effects produced by lifestyle choices, however. You are still the master of your own destiny in that regard. Time wasted in wishing you had a better variant of FOXO3A would be better spent exercising.

A great deal of modern life science research is focused on deciphering the operation of our genes and metabolism. Along the way, researchers are digging up many statistical associations between human life span and specific genetic polymorphisms, such as different alleles of a single gene. This is happening rapidly enough that individual results are no longer newsworthy; this is a data gathering phase in the broader research community, and the data is rolling in. Relentless gains in the cost effectiveness of genetic biotechnologies mean that databases of these associations will grow far faster than they are mined for potential applications and cross-references in the years ahead.

By way of illustration, here are a couple of recent examples of the sort of investigative work into human genetics and longevity that is presently taking place.

The IRS2 Gly1057Asp Variant Is Associated With Human Longevity

Reduced insulin and insulin-like growth factor-1 (IGF-1) signaling extends the life span of invertebrate and mammals. Recently, reduced insulin receptor substrate-2 (IRS2) signaling was found associated with increased longevity in mice. The aim of our study was to evaluate whether a common polymorphism (Gly1057Asp) in human IRS2 gene is associated with human longevity.


Six hundred seventy-seven participants (289 males and 388 females) between 16 and 104 years of age, categorized as long lived (LL; >85 years old) or controls (C; <85 years old), were genotyped for Gly1057Asp-IRS2 locus variability (rs1805097). ... Categorizing participants into percentiles by age, IRS2Asp/Asp participants were more likely to reach extreme old age.

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

Human phagocyte-specific chitotriosidase (CHIT-1) is a chitinolytic enzyme associated with several diseases involving macrophage activation. Previous studies have demonstrated that a high activity of Chit could have widespread effects on atherosclerosis, cardiovascular disease and dementia. The 24-bp duplication in the CHIT-1 gene is associated with a deficiency in enzymatic activity. In this study, we attempted to assess whether CHIT-1 could be a plausible candidate gene responsible for human longevity. Therefore, we compared the distribution of the CHIT-1 polymorphism genotype in three different populations of the Mediterranean area (Italian, Greek and Tunisian) aged over 90 years. As a control group for each nonagenarian and centenarian, a 60-70-year-old subject was genotyped.

We found that the heterozygote frequency for the 24-bp duplication in the CHIT-1 gene was not significantly different among the oldest old subjects of Mediterranean populations, whereas it was significantly different between oldest old subjects and control subjects, being highest among the oldest old subjects and lowest among control groups. In the oldest old group, no subject was observed to be homozygous for CHIT-1 deficiency. Moreover, the mean enzymatic activity in heterozygous oldest subjects was lower than that in the control group. These data indicate that the heterozygosis for a 24-bp duplication in the CHIT-1 gene could have a protective effect in human longevity.

These are fairly typical of the type of associations being uncovered: fairly robust from a statistical perspective, with the putative benefit being small, or specific to narrow aspects of age-related disease or metabolism. That second item, the CHIT-1 gene, is unusual in its uniformity in the oldest subjects of the study. So: yes, some people have better genes than others. But go running or take up calorie restriction rather than dwell upon that fact. You'll end up ahead of the genetically superior couch potatoes of this world by taking that high road.

ResearchBlogging.orgMalaguarnera L, Ohazuruike LN, Tsianaka C, Antic T, Di Rosa M, & Malaguarnera M (2009). Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians. Journal of human genetics PMID: 19881466


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