The genetic component of human longevity: analysis of the survival advantage of parents and siblings of Italian nonagenarians

Abstract

Many epidemiological studies have shown that parents, siblings and offspring of long-lived subjects have a significant survival advantage when compared with the general population. However, how much of this reported advantage is due to common genetic factors or to a shared environment remains to be resolved.We reconstructed 202 families of nonagenarians from a population of southern Italy. To estimate the familiarity of human longevity, we compared survival data of parents and siblings of long-lived subjects to that of appropriate Italian birth cohorts. Then, to estimate the genetic component of longevity while minimizing the variability due to environment factors, we compared the survival functions of nonagenarians' siblings with those of their spouses (intrafamily control group).We found that both parents and siblings of the probands had a significant survival advantage over their Italian birth cohort counterparts. On the other hand, although a substantial survival advantage was observed in male siblings of probands with respect to the male intrafamily control group, female siblings did not show a similar advantage. In addition, we observed that the presence of a male nonagenarians in a family significantly decreased the instant mortality rate throughout lifetime for all the siblings; in the case of a female nonagenarians such an advantage persisted only for her male siblings.The methodological approach used here allowed us to distinguish the effects of environmental and genetic factors on human longevity. Our results suggest that genetic factors in males have a higher impact than in females on attaining longevity.

Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: Cross sectional and longitudinal studies

“…This observation could indicate that the impact of genetic effect becomes more gender-specific during advanced age than at younger ages, and that the genetic effect in old age might be most pronounced for males. Such a difference between genders was recently suggested by Montesanto et al for Italians (Montesanto et al (2011)). …”

Predictors of Exceptional Longevity: Effects of Early-Life and Midlife Conditions, and Familial Longevity

“…This hypothesis of stronger heritability of longevity among males was recently suggested by Italian researchers who studied 202 nonagenarians born around 1910 and their relatives in the province of Calabria, Italy (Montesanto et al 2011). The researchers found that brothers and sisters of male nonagenarians have better survival compared to siblings-in-law of male nonagenarians.…”

“…Numerous studies found that biological relatives of long-lived individuals have a substantial survival advantage compared to relatives of shorter-lived individuals (Pearl and Pearl 1934; Gavrilov and Gavrilova 2001b, 2014; Kerber et al 2001; Gavrilov et al 2002; Willcox et al 2006; Perls et al 2007; Smith et al 2009a), while relatively few studies analyze life span of nonbiological relatives (Schoenmaker et al 2006; Mazan and Gagnon 2007; Westendorp et al 2009; Montesanto et al 2011). At the same time, nonbiological relatives may serve as a nonbiased environmental control group in contrast to the general population control.…”

Human longevity and variation in DNA damage response and repair: study of the contribution of sub-processes using competitive gene-set analysis

“…51 A sex-stratified self-contained setbased analysis of all SNPs investigated showed significance for both males and females (data not shown). Similarly, stratification of the competitive gene-set analysis yielded consistent significance of BER.…”