Living long and ageing well: is epigenomics the missing link between nature and nurture?

Abstract

Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50% of the variability in human lifespan with another 25% explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages.

Towards ageing well: Use it or lose it: Exercise, epigenetics and cognition

“…In a study of 90-year-old male physicians in USA, Yates et al (2008) has shown that maintaining active exercise was an important contributor to good quality ageing for physicians who reached 90 years and beyond, in good health. Similar findings have been reported by Rea et al (2016) who identified, that maintaining exercise and physical activity were important life-style behaviours, self-reported by the nonagenarian sibling participants of the GE netics of H ealthy A geing (GeHA) project (Franceschi et al 2007a) and B elfast E lderly L ongitudinal F ree-living A geing ST udy (BELFAST) (Rea et al 2015), as important contributors to their long and good quality ageing (Rea and Rea 2011, 2013). In their review of fifteen longitudinal studies with at least 5-year follow-up times and a total of 288,724 subjects, aged between 18 and 85 years, Reiner et al (2013) showed that physical activity appeared to have a positive long-term influence on many diseases, including weight gain, obesity, coronary heart disease, type 2 diabetes mellitus, Alzheimer’s disease and dementia.…”

“…In a pooled study of middle-aged 60,000 white males (average age 59 years) with data collected between 1994 and 2012, O’Donovan (2017) concluded that an exercise programme of one or two sessions per week of moderate or vigorous-intensity physical activity may be sufficient to reduce risks for all-cause, cardiovascular and cancer. Rea et al (2016), found that maintaining physical exercise and physical activities thorough out life was a major theme, self-reported by GeHA and BELFAST nonagenarians sibling pairs, as an important factor in their long and good quality ageing.…”

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

“…Increased knowledge is emerging as to how epigenetic modulation can affect cytokine genes with reports linking cytokine epigenetic change to neuroinflammation ( 403 – 405 ). Obesity, smoking, and malnutrition have been shown to have next generational epigenetic effects, and seem likely to contribute to the predilection of offspring developing age-related disease or conversely the longevity phenotype ( 406 – 409 ).…”

Commitment of protein p53 and amyloid-beta peptide (Aβ) in aging of human cerebellum

“…A substantial body of evidence suggests that the lifespan is under genetic control but decades of quest for human longevity genes were not successful. Results of the studies suggest that the epigenetic mechanisms probably play a role in modulating the lifespan [13,23,34]. Moreover, these studies document that the heritability of epigenetic age acceleration in various brain regions is different and that the heritability of age acceleration of the cerebellum appears to be higher than that of the frontal cortex, pons or temporal cortex.…”