Etiology of Individual Differences in Human Health and Longevity

Abstract

In this chapter, we review of the fi eld of gerontological genetics with respect to subjective and objective health, the role of stress on health, and fi nally frailty and longevity. For most indices of subjective and objective health, frailty, and longevity, genetic infl uences contribute only modestly to individual differences, wherein heritabilities are typically on the order of 35%-40%. Notable exceptions are the moderate to strong heritabilities for lipid measures and brain structure and function, with a remarkably increasing role of genetic infl uences for longevity with advancing age. Although candidate gene and genome-wide association studies (GWAS) studies have identifi ed gene variants associated with many subjective and objective health traits, their effect sizes are typically relatively small, as expected for complex traits. There is some evidence for gene-environment interactions, and stress may be an important moderator of genetic variance for health. For example, carrying a risk genotype for cardiovascular disease (CVD) in the angiotensin converting enzyme gene ( ACE ) may predict stress responsivity and risk of cardiovascular-related diagnoses. Moreover, the gene coding for apolipoprotein E ( APOE ) may moderate responsiveness to stress evoking experiences, impact of physical exercise, and associate with sleep characteristics in those who develop cognitive impairments. For metabolic syndrome (MetS), encompassing the co-occurrence of obesity, hypertension, hypertriglyceridemia, 190 ANNUAL REVIEW OF GERONTOLOGY AND GERIATRICS and hyperinsulinemia, promising associations exist although no single genotype or any gene clusters have been consistently associated with MetS across populations, suggesting that complex gene-environment interactions must be understood before the use of genetic markers can be realized in clinical practice. Future investigations of subjective and objective health, frailty, and longevity are needed to further identify sources of genetic and environmental contributionsand their dynamics across adulthood-to advance understanding of aging processes, prevention, and intervention avenues, and ultimately successful aging.

Longitudinal Twin Study of Subjective Health: Differences in Genetic and Environmental Components of Variance Across Age and Sex

“…Sex differences were also evident in the extent of genetic variance across question types, with generally more genetic variance in SH for women than for men. These results suggest that men may rely more on cultural conceptions of health when evaluating their own health, whereas women may rely more on physical health conditions, which reflect greater genetic influences than SH measures (Finkel et al, 2014). One reason for this sex difference in conceptualizations of SH may be the differential experience of physical aging between men and women.…”

“…Twins in these samples shared their rearing socioeconomic status and may have learned healthy lifestyles in their childhood years that continue to influence their behavior in late adulthood (eg, (Seeman & Crimmins, 2001). Most twin research indicates, however, that the impact of rearing environment tends to decrease with increasing age for many traits, including physical health and other relevant components of SH (eg, (Finkel et al., 2014;Reynolds et al, 2005). Additionally, evidence suggests that SH is influenced primarily by recent events or current SES levels, as opposed to distal factors (Manderbacka & Lundberg, 1996;Verropoulou, 2012).…”

“…(Benyamini et al, 2000;Jylhä et al, 1986;Meng & D'Arcy, 2016;Shooshtari et al, 2007;Spuling et al, 2015;Verropoulou, 2012). To the extent that physical health reflects genetic variance (Finkel et al, 2014), genetic components of variance in measures of SH should decline with increasing age as adults focus their attention more on other facets of their health experience, particular their cultural conceptions of "good health," in later adulthood. In very old age, the point at which the graphs in Figure 2 generally demonstrate modest increases in environmental components of variance, physical aspects of aging such as chronic diseases become more important to SH (Jylhä et al, 1986).…”

“…The meaning of "good health," and thus the role of shared environmental variance, may differ between men and women and be differentially elicited by question type. We expect that age changes in genetic and environmental influences on SH will reflect age changes in genetic and environmental influences on physical health (Finkel, Gerritsen, Reynolds, Dahl, & Pedersen, 2014). However, given that the relationship between physical and SH declines with age (Pinquart, 2001), the genetic variance for SH change with age, particularly for items that are more self-comparative versus age-comparative.…”

Molecular genetic contributions to self-rated health

“…Evidence for the heritability of SRH comes from several twin studies, [15][16][17] which provide estimates of the percentage variance explained by genetic factors which range from ~20% to ~60%. 18,19 Studies using molecular genetic methods also provide evidence for heritability: for instance, the genome-wide complex trait analysis (GCTA-GREML) method 20 was used to estimate that common SNPs account for 18% of the variation in SRH (N = 4233). 21 A multivariate twin study 22 indicated appreciable genetic overlap between SRH and the phenotypically-correlated traits of optimism and self-rated mental health.…”