Could physical activity do more for longevity than genes?

The study of longevity genes is a developing science and numerous studies indicate that physical activity has a role in healthy aging.

Genes and longevity

It is estimated that about 25 per cent of the variation in human life span is determined by genetics. The thing is, identifying which genes contribute to longevity is not well comprehended. 

A few common variations (also known as polymorphisms) linked to long life spans are found in the APOEFOXO3, and CETP genes, but they are not found in all individuals with exceptional longevity [1]. It is possible that variants in multiple genes, some of which are unknown, act together to contribute to a long life [2].

Lifestyle and longevity

Longevity and healthy aging in humans are modulated by a combination of genetic and non-genetic elements. Family studies demonstrated that about 25 per cent of the variation in human longevity is because of genetic factors. The search for the molecular and genetic basis of aging has led to the identification of genes associated with the upkeep of the cell and its primary metabolism as the main genetic factors impacting the individual variation of the aging phenotype. 

In addition, analyses on calorie restriction and the variability of genes associated with nutrient-sensing signalling, have shown that an ipocaloric diet and genetically efficient metabolism of nutrients can modulate lifespan by enabling efficient care of the cell and of the organism. 

Recently, epigenetic studies have shown that epigenetic changes, modulated by both genetic background and lifestyle, are very sensitive to the aging process. They can either be a biomarker of the quality of aging or influence the rate and quality of aging [3].

Human longevity and lifestyle

Life expectancy at inception has been rising for most of the last century in western societies – thanks to the continued amelioration of medical assistance, the improvement of the environment (particularly clean, safe water and food) and the advancement of nutrition. 

For example life expectancy in Italy went from 29 years in 1861 to 82 in 2011 [4]. Similarly, extreme longevity has been increasing in these years. 

The figure of centenarians – still in Italy, extraordinarily went up from 165 in 1951 to, more than 15000 in 2011. These results have been attained first by a dramatic reduction of infectious diseases, which, in turn, has dramatically reduced infantile mortality and mortality in adult age.

In fact, in 2011, less than 10 per cent of deaths occurred in subjects under 60 years old, while the corresponding figures were 74 per cent in 1872, 56 pre cent in 1901 and 25 per cent in 1951. Despite that, in the last decades, the continuous extension of lifespan was mainly due to the improvement of medical assistance concerning age-related diseases, especially cardiovascular diseases and cancer, which allowed to increase lifespan of five years in the last two decades and two years in the last ten years [5,6].

These data indicates that environmental factors have a powerful impact on human lifespan and longevity. Yet, lifespan extension seen in the last decades have not been followed by a comparable healthy lifespan extension. 

Surely, in most cases, this lifespan extension is because of the chronicity diseases related to age. This drew the community of biogerontologists to look into interventions, possibly modulated on the knowledge from the studies on the genetic and biomolecular basis of longevity, to extend not only lifespan but also healthy lifespan, or, with a new word, “healthspan”. 

New studies on longevity and physical activity 

Older research shows that low physical activity and greater sitting time are linked to higher death risk. The question is, does risk shift if an individual is genetically inclined to live a long life?

Herbert Wertheim School of Public Health and Human Longevity Science researchers at University of California in San Diego went to answer this in a study published in the online edition of the Journal of Aging and Physical Activitthe in August 24, 2022 y [7]. The research’s objective was to grasp if association between sedentary time and physical activity with demise changed depending on different levels of genetic predisposition for longevity.

Back in 2012, as a section of the OPACH (Women’s Health Initiative Objective Physical Activity and Cardiovascular Health study), researchers started measuring the physical activity of 5,446 women in the United States who were 63 and older, observing them until the year 2020 to look into mortality.

Participants slipped on research-grade accelerometers for up to a week to quantify the time period spent moving, intensity of physical activity, and sedentary time. The study found that higher levels of light physical activity and moderate-to-vigorous activity were linked with a decreased risk of death. 

Higher inactive or sedentary time was connected to an elevated mortality risk. These associations were consistent among women with various levels of genetic longevity affinity.

The study indicated that event if a person is unlikely to live long, as predisposed by their genes, it is still possible to extend life by participating in benefical lifestyle practices like consistent working out and sitting less. Likewise, even if genetics destines you to live a long life, continuing to be physically active is still vital for longevity.

With the aging adult population in the United States, and longer time spent engaging in lower-intensity actions, research findings hold suggestios for older women to partake in physical activity of any intensity to lower the risk of disease and premature death, wrote the authors [8].

Although the common variability accounts for a rather small 25 per cent of human lifespan variability, understanding the genetic basis modulating longevity may give meaningful hints on modulating lifestyle to attain longevity and extend healthspan. That is, a few subjects can achieve longevity because of a lucky combination of polymorphisms that lets them have an efficient metabolism or response to different stress. 

Others can reach a similar result by targeting the same pathways with appropriate lifestyles or interventions. In this context, the significance of epigenetic factors – both as biomarkers of aging and target interventions will undoubtedly grow in the forthcoming future.

[1] https://medlineplus.gov/genetics/gene/apoe/
[2] https://bit.ly/3ViXoxV
[3] https://immunityageing.biomedcentral.com/articles/10.1186/s12979-016-0066-z
[4] https://immunityageing.biomedcentral.com/articles/10.1186/s12979-016-0066-z#Tab1
[5] http://www.mortality.org/
[6] http://www.istat.it/
[7] https://journals.humankinetics.com/view/journals/japa/aop/article-10.1123-japa.2022-0067/article-10.1123-japa.2022-0067.xml?rskey=dRDVlw&result=1
[8] https://today.ucsd.edu/story/physical-activity-may-have-a-stronger-role-than-genes-in-longevity

Photograph: Bojan Milinkov/ShutterStock
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