buffering mechanisms in aging a systems approach toward uncovering the genetic component of aging缓冲机制老化系统的方法对揭示衰老的基因组成部分.pdf

Buffering Mechanisms in Aging: A Systems Approach Toward Uncovering the Genetic Component of Aging 1,2,3* 4 5 1 2,4 Aviv Bergman , Gil Atzmon , Kenny Ye , Thomas MacCarthy , Nir Barzilai 1 Department of Pathology, Albert Einstein College of Medicine, New York, New York, United States of America, 2 Department of Molecular Genetics, Albert Einstein College of Medicine, New York, New York, United States of America, 3 Department of Neuroscience, Albert Einstein College of Medicine, New York, New York, United States of America, 4 Institute for Aging Research Department of Medicine, Albert Einstein College of Medicine, New York, New York, United States of America, 5 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York, United States of America An unrealized potential to understand the genetic basis of aging in humans, is to consider the immense survival advantage of the rare individuals who live 100 years or more. The Longevity Gene Study was initiated in 1998 at the Albert Einstein College of Medicine to investigate longevity genes in a selected population: the ‘‘oldest old’’ Ashkenazi Jews, 95 years of age and older, and their children. The study proved the principle that some of these subjects are endowed with longevity-promoting genotypes. Here we reason that some of the favorable genotypes act as mechanisms that buffer the deleterious effect of age-related disease genes. As a result, the frequency of deleterious genotypes may increase among individuals with extreme lifespan because their protective genotype allows disease- related genes to accumulate. Thus, studies of genotypic frequencies among different age groups can elucidate the genetic determinants and pathways responsible for