Etiology of individual differences in human health and longevity

• In this chapter, we review of the field of gerontological genetics with respect to subjective and objective health, the role of stress on health, and finally frailty and longevity. For most indices of subjective and objective health, frailty, and longevity, genetic influences 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 influences for longevity with advancing age. Although candidate gene and genome-wide association studies (GWAS) studies have identified 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, 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 contributions—and their dynamics across adulthood—to advance understanding of aging processes, prevention, and intervention avenues, and ultimately successful aging.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Annan medicin och hälsovetenskap -- Gerontologi, medicinsk/hälsovetenskaplig inriktning (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Other Medical and Health Sciences -- Gerontology, specialising in Medical and Health Sciences (hsv//eng)

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