How Much Do Genes Determine Lifespan?

How strongly do your genes shape the length of your life? It is a question that has long intrigued us and has been argued over for decades.

For many years, the conclusion appeared clear: genes were thought to explain roughly 20–25% of the differences in human lifespan, while lifestyle and environmental factors accounted for the remainder.

However, fresh research published in Science has questioned that understanding, indicating that the genetic share could be substantially greater.

The researchers say earlier calculations did not properly reflect the way causes of death have shifted over the years. A century ago, many deaths resulted from what scientists describe as extrinsic causes, including accidents, infections and other outside dangers.

Now, at least in developed nations, the majority of people die from intrinsic causes: the progressive decline of the body caused by ageing and age-related conditions such as dementia and heart disease.

Lifespan genes and changing causes of death

To obtain a more accurate estimate, the researchers examined extensive datasets involving Scandinavian twins and deliberately removed deaths caused by external factors. They also assessed twins brought up separately, as well as the siblings of US centenarians.

After excluding deaths due to accidents and infections, the estimated genetic influence rose sharply, increasing from the established 20–25% figure to approximately 50–55%.

The trend is consistent with evidence from individual illnesses. Genetics account for a large share of differences in dementia risk, have a moderate influence on heart disease and make a comparatively limited contribution to cancer.

As living conditions improve, populations grow older and illnesses resulting from the ageing process become more prevalent, the apparent genetic element naturally becomes larger.

Our genes have not become more powerful

Yet this is where the findings need careful interpretation. A larger estimate does not mean that genes have abruptly gained greater power, nor does it suggest that only half of your prospects of reaching old age can be changed. It is the environment that has altered, not our DNA.

Human height provides a useful comparison. One hundred years ago, the height a person reached was greatly influenced by whether they had sufficient food and whether illnesses in childhood restricted their development.

In affluent countries today, almost everybody receives enough nutrition. As those environmental differences have become smaller, genetic variation now accounts for most of the variation in height. This is not because nutrition no longer matters, but because most people can now fulfil their genetic potential.

Still, a child who is malnourished will not grow tall, whatever their genes may be.

The same idea holds true for lifespan. By improving vaccination, cutting pollution, strengthening diets and taking up healthier ways of living, we have reduced the overall effect of environmental influences.

When environmental variation falls, the share of the remaining variation assigned to genetics - termed "heritability" by scientists - rises as a matter of mathematics. The previous estimates were not incorrect; they merely represented a different set of historical conditions.

This points to an essential fact: heritability is not a permanent biological characteristic. Instead, it is a measurement wholly dependent on the population and circumstances under consideration. The familiar 20–25% estimate captured lifespan as it was lived by earlier populations, in which external dangers were significant.

By contrast, the new 50–55% calculation represents a situation in which such threats have mostly been eliminated, effectively measuring a different trait.

What 50% heritable lifespan really means

The headline claim that lifespan is about "50% heritable" could easily be taken to mean that genes dictate half of an individual's chances in life. In practice, the genetic contribution for a particular person may be anything from very limited to very substantial, according to their circumstances.

There are innumerable paths to a long life. Some people possess resilient genetic profiles that offer protection even under difficult conditions; others offset less advantageous genetics with very good nutrition, exercise and healthcare. Every individual has a distinct combination of these elements, and many combinations can lead to remarkable longevity.

The combinations that occur most frequently depend entirely on the population concerned and the conditions in which its members live and grow old. As external causes of death keep declining in the real world - although they will never vanish completely - it will be interesting to observe how these patterns change.

The authors of the new study acknowledge that around half of variation in lifespan remains dependent on environment, lifestyle, healthcare and random biological events, such as cells growing uncontrollably in cancer. They contend that their findings should reinvigorate attempts to identify the genetic mechanisms behind ageing and longevity.

Working out how varied genetic factors interact with different environments is likely to be central to understanding why certain people live far longer than others.

The study provides important insight into the ways different forms of mortality have influenced our understanding of lifespan. Its findings are better interpreted as evidence that heritability shifts between contexts, rather than as proof of one universal genetic contribution to the length of our lives.

Ultimately, both genes and environment are important. More importantly still, they matter in combination. Whether that seems reassuring or discouraging, there is unlikely ever to be a straightforward answer to how much of your lifespan genes alone determine.

Karin Modig, Associate Professor, Epidemiology, Karolinska Institutet

This article is republished from The Conversation under a Creative Commons licence. Read the original article.