It is interesting to compare the level of interest in mapping genetic variations to effects on aging and life expectancy with the results of studies that use the largest databases of genetic material. The more data used, the more it becomes apparent that gene variants have very little effect on life expectancy, considered across the breadth of the population. The average person is very little different from their associates when it comes to the interaction between genotype and mortality risk. The effects of lifestyle choices far outweigh the effects of genes.
There are rare genetic variants capable of bestowing additional years of life. The small effect of genetics on life expectancy is the consequence of the fact that neither you, I, nor near the the entire population of the world is blessed with such a variant. Yet even looking at the inherited mutation with the largest known effect size on mortality risk in humans, PAI-1 loss of function, which appears to influence the late life burden of cellular senescence and adds seven years of life expectancy for the very few people known to exhibit it, that is still a gain that that most people could achieve via suitable lifestyle choices. Exercise a great deal more, eat a very optimal diet, and so forth.
Lifestyle and environmental factors affect health and ageing more than our genes
Researchers used data from nearly half a million UK Biobank participants to assess the influence of 164 environmental factors and genetic risk scores for 22 major diseases on ageing, age-related diseases, and premature death. Environmental factors explained 17% of the variation in risk of death, compared to less than 2% explained by genetic predisposition (as we understand it at present). Of the 25 independent environmental factors identified, smoking, socioeconomic status, physical activity, and living conditions had the most impact on mortality and biological ageing. Early life exposures, including body weight at 10 years and maternal smoking around birth, were shown to influence ageing and risk of premature death 30-80 years later. Environmental exposures had a greater effect on diseases of the lung, heart and liver, while genetic risk dominated for dementias and breast cancer.
Integrating the environmental and genetic architectures of aging and mortality
Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging. These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors.
Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points. Polygenic risk explained a greater proportion of variation (10.3-26.2%) compared with the exposome for incidence of dementias and breast, prostate, and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5-49.4%) compared with polygenic risk for incidence of diseases of the lung, heart, and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk.
View the full article at FightAging
