Individuals that avoid age-related diseases into later life are known as 'exceptional survivors', and have increased longevity compared to their 'controls' (those that were born at a similar time, yet have 'aged' and died sooner). The Leiden Study determined that in these long-lived individuals there is a considerable genetic component contributing to the survival [Schoenmaker et al] (although this could equally be epigenetic - or even more likely, a combination of both).
I have read about studies that have identified genetic mutations that cause premature aging phenotypes (for instance mutations in the WRN gene cause Werner's Syndrome [Yu et al]).
I have yet to discover any studies that determine any genes/regions associated with resistance to age-related disease (i.e. those that age 'well'). My question is whether anyone knows of any such studies?
Arguably studies that have looked into predisposition to age-related diseases have found some mutations - for instance mutations within the 9p21 genetic locus (i.e. p16INK4a/CDKN2A) have been associated with heart disease and stroke independently (2 age-related diseases) [Wahlstrand et al]. Therefore individuals without any of these risk-increasing alleles could be considered predisposed to exceptional survival - but I see this as separate to my question. Are there any protective alleles/genes/loci that increase 'global' survival? Are there a few protective alleles, or many with small effects? Or are the exceptional survivors just without any disease-causing/risk-increasing alleles?
I am interested in published research (of course), but also in peoples general perceptions of the topic; there are plenty of theories of aging and longevity, but few facts - so please state what you 'believe', and explain why this is the case.
Thanks for your time.
p.s. I am aware that you can genetically modify lab models (e.g. C. elegans eat-2 mutants [Lakowski et al]) to live longer. I am interested in naturally occurring variants, specifically in humans (or that at least relate to human aging).
Update (11 May 2012)
I have found a study, published earlier this year, that finds a single genetic polymorphism to be associated (after correction for multiple testing) with centenarians [Sebastiani et al]. The SNP is in TOMM40/APOE (in LD), which is certainly interesting given the previous links between APOE and Alzheimer's (an age-related disease).
However, I am not convinced by the experimental design; they use age-at-death in centenarians as their cases (having genotyped them), and they use alive population controls as the controls. Whilst there is unlikely all these individual will become long-lived, a better design (to gain more power) would have been to use individuals who have died from 'premature' (e.g. between 60 and 70) age-related disease. So I am still waiting for a convincing study, but this does look promising!