Genomics of ageing in twins

Abstract

Ageing is a complex multifactorial process, reflecting the progression of all degenerative pathways within an organism. Due to the increase of life expectancy, in recent years, there is a pressing need to identify early-life events and risk factors that determine health outcomes in later life. So far, genetic variation only explains ~20–25 % of the variability of human survival to age 80+. This clearly implies that other factors (environmental, epigenetic and lifestyle) contribute to lifespan and the rate of healthy ageing within an individual. Twin studies in the past two decades proved to be a very powerful tool to discriminate the genetic from the environmental component. The aim of this review is to describe the basic concepts of the twin study design and to report some of the latest studies in which high-throughput technologies (e.g. genome/epigenome-wide assay, next generation sequencing, MS metabolic profiling) combined with the classical twin design have been applied to the analysis of novel ‘omics’ to further understand the molecular mechanisms of human ageing.

Back to the future: Epigenetic clock plasticity towards healthy aging

“…In other words, the chronological age of two individuals may be the same, however there could be significant differences in their biological age. Studies in monozygotic twins have shed light on the relative contribution of genetic and non-genetic (shared and unique environmental) factors in aging [2,3]. The heritability of longevity lies around 25%, suggesting an important role for environmental and lifestyle factors [4,5].…”

Food and Nutrition Education for Healthy Life at Retirement and Graceful Aging

“…Aging of an individual is influenced by genetic and environmental factors. It has been projected that environmental factors may account for as much as 75% of the aging process (Steves, 2012, Mangino 2014. Good nutrition throughout the lifespan supports healthy aging (Mathers, 2013).…”

The heritable path of human physical performance: from single polymorphisms to the “next generation”

“…Instead of focusing on extremely limited regions of the genome as simple association studies, GWAS investigate associations between phenotypes of interest and genetic variability in a more unbiased manner throughout the genome because the study is not as limited by investigating only hypothesis‐driven candidate genes (Kim et al., ; Pitsiladis et al., ). GWAS do include the screening of candidate genes, whose results must be replicated and confirmed in other populations to be considered strong evidence of positive genetic association (Manolio, ; Mangino, ). In addition, these screenings may offer a wide range of possibilities for further investigations, including genotype–phenotype studies in exercise physiology.…”

“…Of note, given that epigenetic changes are used to regulate tissue‐specific gene expression, epigenetic alterations found in blood cells in response to exercise might not reflect similar changes in muscle fibers or endothelial cells, although they may reflect important physiological changes or can indirectly serve as useful biomarkers in particular cases. It also should be noted that epigenetic changes may be long‐lasting (Kaliman et al., ; Mangino, ) and may help explain the influence of physical activity on the longevity and muscle fiber composition of individuals. Moreover, some of these epigenetic changes may be transmitted to offspring (Ahmetov et al., ).…”

“…Initial studies on physical performance aimed to indirectly evaluate the genetic basis of human physical performance through heritability estimates attributable to genes, using variability in phenotypic traits of individuals in family studies, especially those comparing such traits in monozygotic and dizygotic twins (Komi et al., ; Fagard et al., ; Sundet et al., ; Bouchard et al., ; Calvo et al., ; Mangino, ). For instance, the genomic component may account for up to 90% of the variance in maximal oxygen uptake (VO 2max ) and the proportion of different types of muscle fibers in twins (Bouchard, ; Pitsiladis et al., ).…”