Dataset Information

Genetic, Social, and Lifestyle Drivers of Healthy Aging and Longevity.

ABSTRACT:

Purpose of review

"Healthy aging" is the state of the aging process in which a person can maintain physical, social, mental, and spiritual wellness. This literature review presents an overview of recent studies that explore how biological, social, and environmental factors contribute to healthy aging.

Recent findings

A number of genome-wide association studies have been conducted recently for traits related to healthy aging, such as frailty index, healthspan, muscle strength, and parental longevity, leading to the discovery of dozens of genetic variants associated with these traits. In parallel, associations between healthy aging measures and multiple non-biological environmental elements have been identified as key moderators of the aging process, indirectly influencing day-to-day homeostatic processes.

Summary

Individual variations in lifespan and healthspan are influenced by genetic factors, with a heritability of ~ 25% in developed countries. Non-genetic risk variance is explained in part by social, cultural, and lifestyle conditions. Altogether, these factors contribute to a multifaceted state of wellness over time, shaping individual risk to frailty and resilience during the aging process. Notably, "Blue Zone" populations, which are characterized by an abundance in healthy lifestyles across generations, share some commonalities regarding determinants of health.

SUBMITTER: Castruita PA

PROVIDER: S-EPMC10686287 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Genetic, Social, and Lifestyle Drivers of Healthy Aging and Longevity.

Castruita Patricia Alejandra PA Piña-Escudero Stefanie Danielle SD Rentería Miguel E ME Yokoyama Jennifer S JS

Current genetic medicine reports 20220926 3

<h4>Purpose of review</h4>"Healthy aging" is the state of the aging process in which a person can maintain physical, social, mental, and spiritual wellness. This literature review presents an overview of recent studies that explore how biological, social, and environmental factors contribute to healthy aging.<h4>Recent findings</h4>A number of genome-wide association studies have been conducted recently for traits related to healthy aging, such as frailty index, healthspan, muscle strength, and ...[more]

PMID: 38031561

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Project description:Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and rare alleles, with impeccable control for population stratification and consideration of non-genetic factors such as environment.

Project description:ImportanceGenetic and lifestyle factors contribute to an individual's risk of developing Alzheimer's disease. However, it is unknown whether and how adherence to healthy lifestyles can mitigate the genetic risk of Alzheimer's.ObjectiveThe aim of this study is to investigate whether adherence to healthy lifestyles can modify the impact of genetic predisposition to Alzheimer's disease on later-life cognitive decline.Design setting and participantsThis prospective cohort study included 891 adults of European ancestry, aged 40 to 65, who were without dementia and had complete healthy-lifestyle and cognition data during the follow-up. Participants joined the Wisconsin Registry for Alzheimer's Prevention (WRAP) beginning in 2001. We conducted replication analyses using a subsample with similar baseline age range from the Health and Retirement Study (HRS).ExposuresWe assessed participants' exposures using a continuous non-APOE polygenic risk score for Alzheimer's, a binary indicator for APOE-ε4 carrier status, and a weighted healthy-lifestyle score, including factors such as no current smoking, regular physical activity, healthy diet, light to moderate alcohol consumption, and frequent cognitive activities.Main outcomes and measuresWe z-standardized cognitive scores for global (Preclinical Alzheimer's Cognitive Composite score 3 - PACC3) and domain-specific assessments (delayed recall and immediate learning).ResultsWe followed 891 individuals for up to 10 years (mean [SD] baseline age, 58 [6] years, 31% male, 38% APOE-ε4 carriers). After false discovery rate (FDR) correction, we found statistically significant PRS × lifestyle × age interactions on preclinical cognitive decline but the evidence is stronger among APOE-ε4 carriers. Among APOE-ε4 carriers, PRS-related differences in overall and memory-related domains between people scoring 0-1 and 4-5 regarding healthy lifestyles became evident around age 67 after FDR correction. These findings were robust across several sensitivity analyses and were replicated in the population-based HRS.ConclusionA favorable lifestyle can mitigate the genetic risk associated with current known non-APOE genetic variants for longitudinal cognitive decline, and these protective effects are particularly pronounced among APOE-ε4 carriers.

Dataset Information

Genetic, Social, and Lifestyle Drivers of Healthy Aging and Longevity.

Purpose of review

Recent findings

Summary

Publications

Genetic, Social, and Lifestyle Drivers of Healthy Aging and Longevity.

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