Physical activity is seen as a way to extend the human lifespan, but Finnish twin studies found the benefits of physical activity for longevity may not be as straightforward as has been previously thought.

Researchers from the University of Jyväskylä, Finland, investigated the links between long-term leisure-time physical activity and mortality, as well as whether physical activity can mitigate the increased risk of mortality due to genetic predisposition to diseases. Moreover, they examined the relationship between physical activity and later biological aging.

The study included 22,750 Finnish twins born before 1958 whose leisure-time physical activity was assessed in 1975, 1981 and 1990. Mortality follow-up continued until the end of 2020.

Moderate activity yields maximum longevity benefits

Four distinct sub-groups were identified from the data, which was based on leisure-time physical activity over the 15-year follow-up: sedentary, moderately active, active and highly active groups. When the differences in mortality between the groups were examined at the 30-year follow-up, it was found that the greatest benefit – a 7% lower risk of mortality – was achieved between the sedentary and moderately active groups. A higher level of physical activity brought no additional benefit. When mortality was examined separately in the short and long term, a clear association was found in the short-term: the higher the level of physical activity, the lower the mortality risk. In the long term, however, those who were highly active did not differ from those who were sedentary in terms of mortality.

An underlying pre-disease state can limit physical activity and ultimately lead to death, not the lack of exercise itself. This can bias the association between physical activity and mortality in the short term.”

Elina Sillanpää, Associate Professor from the Faculty of Sports and Health Sciences

Meeting physical activity guidelines does not guarantee a lower mortality risk

The researchers also investigated whether following the World Health Organization’s physical activity guidelines affects mortality and genetic disease risk. The guidelines suggest 150 to 300 minutes of moderate or 75 to 150 minutes of vigorous activity weekly. The study found that meeting these guidelines did not lower mortality risk or alter genetic disease risk. Even for twins who met the recommended levels of PA over a 15-year period, no statistically significant difference in mortality rates was found compared to their less active twin pair.

“The widely observed favorable association between physical activity and mortality are based on observational studies that are prone to bias from different sources,” says postdoctoral researcher Laura Joensuu from the Faculty of Sports and Health Sciences. “In our studies, we aimed to account for various sources of biases, and combined with the long follow-up period, we could not confirm that adhering to physical activity guidelines mitigates genetic cardiovascular disease risk or causally reduces mortality.”

Link between physical activity and biological aging is U-shaped

For the subsample of twins, biological aging was determined from blood samples using epigenetic clocks. Epigenetic clocks allow a person’s biological aging rate to be estimated based on methyl groups that regulate gene expression and are linked to aging process.

“We found that the association between leisure-time physical activity and biological aging was U-shaped: Biological aging was accelerated in those who exercised the least and the most,” says Sillanpää.

Other lifestyles, such as smoking and alcohol consumption, largely explained the favorable associations of physical activity with biological aging.

Genetic data were available for 4,897 twins. The genetic susceptibility of twins to coronary artery disease, as well as systolic and diastolic blood pressure was assessed using new polygenic risk scores, which sum the genome-wide susceptibility to morbidity. In addition, all-cause and cardiovascular mortality was followed in 180 identical twin pairs. The biological aging rate of 1,153 twins was assessed from a blood sample.

The studies were carried out in cooperation with the Faculty of Sport and Health Sciences and Methodology Centre for Human Sciences at the University of Jyväskylä and the Finnish Institute of Molecular Medicine at the University of Helsinki.

The first authors of the studies, doctoral researchers Laura Joensuu and Anna Kankaanpää, belong to the GenActive research group. The GenActive group investigates genetic and lifestyle factors that predict biological aging, health and functional capacity. The group leader is Elina Sillanpää, associate professor of health promotion.

The research was funded by the Research Council of Finland, Juho Vainio Foundation, Päivikki and Sakari Sohlberg Foundation, Sigrid Juselius Foundation and Yrjö Jahnsson Foundation.