Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice

Abstract

SignificanceAging-associated diseases are increasingly common in an aging global population. However, the contributors and origins of differential risk for unhealthy aging remain poorly understood. Using a mouse model, we found that offspring of aged fathers exhibited a reduced life span and more pronounced aging-associated pathologies than animals sired by young fathers. Tissue of offspring and aged fathers revealed shared epigenetic signatures and showed altered activation states of longevity-related cell signaling. Our results suggest that variability in aging trajectories could derive, in part, from the age at conception of the father, a possibility that warrants human epidemiological investigation.

Increasing paternal age alters anxiety‐related behaviour in adult mice

“…Exploration is a behavioural domain that is complexly mediated, and as such APA effects on exploration may be the result of multiple APA‐related mutations that are dispersed throughout the genome. However, this is unlikely to explain the robust phenotype seen in the present study, suggesting that a more conserved mechanism of age‐related epigenetic alterations is inherited …”

Strain‐specific effects of parental age on offspring in Drosophila melanogaster

“…Generally, the lifespan of offspring has been reported to be decreased by parental aging and has been referred to as a "Lansing effect". This effect has been shown in various species, such as plant (Ashby & Wangermann 1954), yeast (Muller 1985), rotifer (Lansing 1954), Drosophila (O'brian 1961Priest et al 2002;Somashekar & Krishna 2011), mouse (Tarín et al 2005;Xie et al 2018), and even human (Gavrilov et al 1996). However, a positive effect of parental aging on lifespan has been reported.…”

“…), body weight, sexual maturation, hormone production (Wang & vom Saal ), and lifespan (Xie et al . ). In addition, offspring from old parents showed an increased mortality during the egg stage in Caenorhabditis elegans (Beguet & Brun ), as well as increased development time from egg to adult in flour beetle Tribolium confusum (Raychaudhuri & Butz ).…”

“…Similar to results in humans, many reports using animal models have shown detrimental effects of parental age. In mice, offspring from old parents were reported to exhibit decreased social and exploratory behaviors (Smith et al 2009), body weight, sexual maturation, hormone production (Wang & vom Saal 2000), and lifespan (Xie et al 2018). In addition, offspring from old parents showed an increased mortality during the egg stage in Caenorhabditis elegans (Beguet & Brun 1972), as well as increased development time from egg to adult in flour beetle Tribolium confusum (Raychaudhuri & Butz 1965).…”

Intergenerational transmission of longevity is not affected by other familial factors: Evidence from 16,905 Dutch families from Zeeland, 1812-1962

“…The link between number of offspring and age at death itself is weak at best (Helle, Lummaa & Jokela, 2005;Hurt, Ronsmans & Thomas, 2006;Le Bourg, 2007) and seems to be strongly dependent on parental health and mortality during childbearing ages (Doblhammer & Oeppen, 2003). However, number of offspring is associated with short birth intervals and parental ageing, which are known to affect offspring survival (Dewey & Cohen, 2007;Gavrilov & Gavrilova, 2000;Kozuki et al, 2013;Xie et al, 2018). Giving multiple births in rapid succession can deplete a woman, due to increased exposure to stress, additional energy requirements, and having less time to recover (Engelen & Wolf, 2011;Winkvist, Rasmussen & Habicht, 1992).…”