UNFOLDING THE SECRETS OF EXCEPTIONAL LONGEVITY

• Published in: Innovation in aging 2018-11, Vol.2 (suppl_1), p.759-759
• Main Author: Barzilai, N
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 2399-5300; 2399-5300
• DOI: 10.1093/geroni/igy023.2807

A watershed moment in Gerontology occurred when it was demonstrated that altering a single gene in an organism can have a significant impact on the lifespan and health-span. A natural progression from this discovery was to ask whether human centenarians, who age slower and may live twice as long as their contemporaries, also harbor genes that explain their successful aging. This led us to embark on an in depth study of the phenotypes and the genome of families with exceptional longevity, including >670 centenarians. Over the course of two decades we discovered that centenarians who are also protected from the negative effects of aging and are generally healthy until the end of their life span, do not follow unique lifestyles or diets, and do not have the ‘perfect’ genome. While they harbor many mutations/SNPs known to cause diseases, such as cancer and Alzheimer’s disease, they donot manifest these and neither do their offspring. This highlighted the importance of discovering resilience genes and pathways that protect from aging and disease causing genes. It led to our discoveries of a variety of genetic alterations in the growth hormone pathway in centenarians and demonstrated that reduced function of this pathway is associated with protection from aging. Several other resilience genes have been identified in this cohort, including genes that regulate lipid metabolism. Centenarians exemplified that evolutionary conserved and non-conserved mechanisms are associated with extended human health- and life-span, with some of our findings already translated by pharmaceuticals to drugs that potentially target aging.