Centenarian: Epigenomic resilience to environmental challenges

Aging increases the risk for numerous chronic diseases. Centenarians on the other hand, are a unique segment of the population, who exhibit long human life- and health-span, despite practicing similar life style habits as their peers. One hypothesis to explain their longevity proposes that they have a ‘perfect’ genome that is deplete of disease causing gene variants. Another one suggested Epigenetics (acquired or heritable changes in gene function or phenotypes without changes in DNA sequence) as an important factor in aging. Epigenetic changes (especially changes in methylation pattern with age) may represent one of the central mechanisms of gene regulation by which many aging process are buffered, and therefore facilitate healthy lifespan through modulating gene expression and disease risk. We utilized state of the art technologies to obtain significant information on epigenomic changes in methylation with aging, and tested it in both a cross-sectional and longitudinal study. We used two centenarian cohorts (IMECS and Longevity) to probe into the hallmarks of healthy aging. This data was analyzed in a meaningful way, by assessing the occurrence of age-related diseases and its interaction with either supportive or adverse environments (i.e. epigenetic influence). This study opened the horizons for more specific and functional studies, as previously exemplified by numerous genetic studies, and led to a better understanding of the biology of aging. Successful interpretation may lead to future crafting of treatments and interventions, which will promote aging with grace.