Genomes of centenarians yield new genes associated with long life

Researchers have reported finding new genes associated with living an unusually long life, according to a study in PLOS Genetics. Previously, scanning the genomes of centenarians to identify longevity genes has produced very few results. By developing a statistical method which incorporates information about genetic risk of developing fatal diseases, the researchers pulled out five new genes associated with living far longer than normal.

 

Dr. David Cutler, Associate Professor, Department of Human Genetics, Emory University (webpage):

Expertise: population genetics applications to human disease studies, analyzing whole genome data sets to discover genetic variants associated with disease.

According to the title of a 2014 movie by Seth MacFarlane, there are ‘A Million Ways to Die in the West.’  While certainly not germane to his concerns, Mr. MacFarlane is probably underestimating the number of ways one can die, when in truth, there may be a nearly uncountable number of ways to die everywhere.

“Today’s paper by Kristen Fortney and colleagues forces us to confront the question ‘what is longevity?’ Is it a trait unto itself? Or is it the summation of ‘avoiding death by a million causes?’  The authors look for genetic variants associated with exceptionally long life and find very little evidence for any, other than the well-known APOE locus, where alleles are known to be associated with heart disease and Alzheimer’s disease.   This is perhaps not surprising when we imagine that differing genes are involved in avoiding the million different ways to die, and that no single gene has a disproportionately large effect on living a long time (other than perhaps APOE which still has only a very, very modest effect).

“After showing that there are no genes with strong effects on longevity, the authors go on to show that several alleles, which have previously been reported to be weakly associated with fatal diseases, are also even more weakly associated with overall longevity. In other words, if allele A is associated with a slightly increased risk of fatal disease and therefore dying younger, the opposite of allele A is associated with a slight propensity to live longer. This is perhaps not surprising either, and is in an general support of the MacFarlane thesis:  there are a million ways to die, and alleles that are associated with any fatal disorder are probably weakly associated with not living to great age.”

 

Dr. Richard Cawthon, Research Associate Professor, Human Genetics, University of Utah (webpage):

Expertise: genetics of human aging.

“This important study by Fortney et al. takes a back to the future approach, revisiting an old idea in gerontogenetics that might otherwise have remained dormant, and applying the latest genotyping and novel statistical approaches to mine a large number of Genome Wide Association Studies (GWAS) of aging-related diseases for genetic loci harboring single nucleotide polymorphisms (SNPs) that significantly influence one’s chances of achieving exceptional longevity.

“More than 30 years ago, the hypothesis was put forward that the loci responsible for several inherited syndromes thought to resemble accelerated aging would also harbor additional genetic variants with the opposite effect, i.e. slowing aging and increasing one’s chances of staying healthy to a very advanced age (see Martin GM, Syndromes of accelerated aging).  The small number of studies that initially investigated this hypothesis failed to find much support for it, and there have been few studies looking into it in recent years (however, see Conneely et al. Human longevity and common variations in the LMNA gene: a meta-analysis).

“Fortney et al. now show that when a genetic locus on its own has been found in GWA studies to be associated with two or more major aging-related diseases and/or quantitative traits associated with the risk of major aging-related diseases, it is a good candidate for being relatively depleted of those alleles in exceptionally long-lived people.  Some of these pathogenic variants may simply be so damaging that their presence greatly lowers the chances of achieving exceptional longevity; but some may directly regulate the rates of fundamental processes of aging, providing clues to where medical interventions might best be targeted to dramatically increase human healthspans and lifespans.”

 

Declared interests (see GENeS register of interests policy):

No interests declared

 

Reference

Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity‘ by Kortney et. al., published in PLOS Genetics on Thursday 16 December, 2015.

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