What part do our genes play in our lifespan? Previous studies have assumed that lifestyle and environmental conditions primarily influence how old we get. However, a new study now shows that the influence of genes has probably been significantly underestimated so far. Extrinsic causes of death such as accidents and infections often obscure how old a person could actually have become. When the researchers calculated these factors out, they arrived at a heritable share of lifespan of 55 percent – more than twice as much as previously assumed. The results show that the search for genes that promote longevity can be worthwhile.
Are our chances of a long life particularly high if our parents and grandparents lived to old age? Or do our lifestyle and environment play a bigger role? Aging research has been concerned with this question for a long time. To find an answer to this, twin studies and family tree analyzes are often used. But the results vary widely depending on the methodology. “Current estimates based on twin studies show a heritability of only 20 to 25 percent, and current large-scale family tree studies suggest that it is as low as 6 percent,” reports a team led by Ben Shenhar from the Weizmann Institute of Science in Israel.
But most of these studies have a serious flaw: They often rely on data from people who were born in the 18th or 19th centuries and who often died at a young age due to infectious diseases, accidents or other external causes that play a much smaller role today than they did back then. “Such deaths, which have nothing to do with genetic predisposition, falsify the estimate of the heritable proportion of lifespan,” explain the researchers.
Extrinsic causes of death excluded
In order to estimate the influence of genes more reliably, Shenhar and his team re-evaluated three large twin studies from Scandinavia and also included data on the siblings of 100-year-olds from the USA. For their analysis, the researchers calculated premature deaths due to infections, accidents, etc. What remained were so-called intrinsic causes of death. “This intrinsic mortality results from processes within the body, including genetic mutations, age-related diseases and the decline in physiological functions with increasing age,” explains the team.
It turned out that if you only look at deaths that are actually related to age, the heritable portion of lifespan is 55 percent – more than twice as much as previously assumed. According to Shenhar and his colleagues, this value is realistic because around half of many other human physiological characteristics also depend on genes. Even in mice that were kept under controlled conditions, there was a genetic influence on lifespan of around 55 percent.
Interaction between genes and environment
According to the study, genetic inheritance includes, among other things, the risk of cardiovascular diseases and dementia – both important factors for mortality. In the case of cancer, another common cause of death, the hereditary proportion is slightly lower, probably because external risk factors play a larger role. In general, the remaining differences in lifespan that cannot be explained genetically are likely due to environmental factors, including lifestyle, socioeconomic influences and access to health care, according to the researchers. Epigenetic modifications could also play a role.
“The study has important implications for aging research,” write Daniela Bakula and Morten Scheibye-Knudsen from the University of Copenhagen in an accompanying commentary in Science. “A significant genetic contribution strengthens the rationale for large-scale efforts to identify variants associated with longevity.” In this way, it may be possible to uncover biological signaling pathways that explain why some people live particularly old.
Source: Ben Shenhar (Weizmann Institute of Science, Israel) et al., Science, doi: 10.1126/science.adz1187