Transgenerational Inheritance of Longevity: An Epigenetic Phenomenon?

Copyright: © 2013 Vaiserman AM . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Over the past decade, there is substantive evidence that adverse consequences of early-life environmental stresses, such as chemicals or diet, can be passed from the first generation to the next [1]. The environmentally induced transgenerational inheritance has been shown for obesity in mice [2], reproductive disease in rat [3,4], and human colorectal cancer [5]. There is some evidence that maternal in utero exposure to the Dutch famine of 1944-45 is associated with increased neonatal adiposity and poor health in later life in F2 generation offspring [6]. Transgenerational effects of the early-life nutritional conditions on the human longevity were also revealed. By the analysis of the data collected by following-up a cohort born in 1905 in Sweden, it has been found that ancestors’ early-life nutrition can determine longevity of their offspring [7]. The probands’ longevity was influenced by their paternal grandfathers’ access to food, but only during the grandfather’s slow growth period before the prepubertal peak in growth velocity and a period of relatively low need for food. It has been also reported that the father’s poor food supply and the mother’s good food supply were associated with a lower risk of cardiovascular death [8]. More recently, transgenerational correlations between food supply in early life of the paternal grandparents and the grandchild’s longevity including associations with cardiovascular and diabetic deaths were documented [9-11]. Results obtained by the Modin et al. [12] showed that the social disadvantage imposed on those born outside wedlock in early twentieth century Sweden appears to be reproduced as a health disadvantage in their children and grandchildren, with likely consequences for offspring mortality. Specifically, men and women born outside wedlock were at an increased risk of adult mortality and men were also significantly less likely to reach their 80th birthday compared to those who were born in wedlock. These effects were transmitted to their children and grandchildren potentially influencing longevity and mortality risk in these generations. These data led to the suggestion that epigenetic modifications (heritable changes in gene expression not encoded by the DNA sequence) can be passed through generations, and transgenerationally transmitted abnormal epigenetic states (epimutations) are associated with disease in both humans and animals.