Why Is Parental Lifespan Linked to Children’s Chances of Reaching a High Age? A Transgenerational Hypothesis

Abstract

A B S T R A C TPurpose: Transgenerational determinants of longevity are poorly understood. We used data from four linked generations (G0, G1, G2 and G3) of the Uppsala Birth Cohort Multigeneration Study to address this issue. Methods: Mortality in G1 (N = 9565) was followed from 1961-2015 and analysed in relation to tertiles of their parents' (G0) age-at-death using Cox regression. Parental social class and marital status were adjusted for in the analyses, as was G1's birth order and adult social class. For an almost entirely deceased segment of G1 (n = 1149), born 1915-1917, we compared exact age-at-death with G0 parents' age-at-death. Finally, we explored 'resilience' as a potentially important mechanism for intergenerational transmission of longevity, using conscript information from psychological interviews of G2 and G3 men. Results: G0 men's and women's ages-at-death were independently associated with G1 midlife and old age mortality. This association was robust and minimally reduced when G0 and G1 social class were adjusted for. We observed an increased lifespan in all social groups. Median difference in age-at-death for sons compared to fathers was + 3.9 years, and + 6.9 years for daughters compared to mothers.Parents' and maternal grandmother's longevity were associated with resilience in subsequent generations. Resilience scores of G2 men were also associated with those of their G3 sons and with their own mortality in midlife. Conclusions:The chance of reaching a high age is transmitted from parents to children in a modest, but robust way. Longevity inheritance is paralleled by the inheritance of individual resilience. Individual resilience, we propose, develops in the first part of life as a response to adversity and early experience in general. This gives rise to a transgenerational pathway, distinct from social class trajectories. A theory of longevity inheritance should bring together previous thinking around general susceptibility, frailty and resilience with new insights from epigenetics and social epidemiology.

A meta-analysis of genome-wide association studies of epigenetic age acceleration

“…Nominally significant genetic correlations between Hannum-based, but not Horvath-based, epigenetic age acceleration, and lifestyle factors such as smoking behaviour and education level, provide some evidence for a genetic basis underlying the phenotypic results we reported previously (18), and provide tentative support to the hypothesis that Hannum-based epigenetic ageing is relatively sensitive to changes in environment and lifestyle. Father’s age at death, a rough proxy for lifespan (46), was nominally significantly correlated with both EAA measures, and parents’ age at death was additionally correlated with Hannum-EAA, consistent with a body of work demonstrating robustly that EAA predicts life span (10,11). Aside from these, genetic correlations with age-related traits were surprisingly few: it is possible that this could reflect an overly conservative correction for the multiple tests carried out, or low statistical power, rather than a genuine lack of correlations ( Table D in S1 Data ).…”

A meta-analysis of genome-wide association studies of epigenetic age acceleration

“…Nominally significant genetic correlations between Hannum-based, but not Horvath-based, epigenetic age acceleration, and lifestyle factors such as smoking behaviour and education level, provide some evidence for a genetic basis underlying the phenotypic results we reported previously [19], and provide tentative support for the hypothesis that Hannum-based epigenetic ageing is relatively sensitive to changes in environment and lifestyle. Father’s age at death, a rough proxy for lifespan [59], was nominally significantly correlated with both EAA measures, and parents’ age at death was additionally correlated with Hannum-EAA, consistent with a body of work demonstrating robustly that EAA predicts life span [10,12]. Aside from these, genetic correlations with age-related traits were surprisingly few: it is possible that this could reflect an overly conservative correction for the multiple tests carried out, or low statistical power, rather than a genuine lack of correlations ( S4 Table ).…”

Food abundance in men before puberty predicts a range of cancers in grandsons

“…Secondly, we considered social confounding: Social continuity in advantage/disadvantage across generations, partly driven by family influences on children's and grandchildren's education and health, is a well-known phenomenon in the sociological literature 49,50 . The early social and family environment does indeed predict health in successive generations in the Uppsala Multigeneration Study database 49,51 .…”

“…Their children who survived until the Census of 1960 could be followed-up and constitute generation 2 (G2, born 1932-1990). The grandparental generation, denoted as generation 0 (G0, born 1851-1914), was manually traced back from generation 1 by means of parish registers, hospital archives and the Swedish Death Index (6th edition compiled by genealogists and Statistics Sweden) 35,51 . We included only G2 and G1 men and women for whom there was information about two or more G0 ancestors, maternal or paternal.…”