New study reveals greater role of genetics in human longevity

(Patria) - Many factors influence the length of your life, such as diet, exercise, smoking, drinking, environment... But what about your genes? This has been a controversial question for decades.

A new study indicates a greater role for genetics than previous research has suggested, estimating the contribution of genes to determining human lifespan at about 50 percent.

This is roughly double what previous studies have shown and reflects findings from lifespan studies in laboratory animals.

- Lifespan is undoubtedly shaped by many factors, including lifestyle, genes, and importantly, chance – take genetically identical organisms raised in similar environments that die at different times, for example – said Ben Shenhar, a physics doctoral student at the Weizmann Institute of Science in Israel and lead author of the study published on Thursday in the journal Science.

- In our work, we tried to explain the amount of variation between different people that can be attributed to genetics. Our study tried to divide longevity factors into genetics and 'everything else'. 'Everything else' accounts for about 50 percent – Shenhar explained.

The researchers sought to explain a confounding factor in previous studies that used Swedish and Danish twins, most of which date back to the 19th century.

Those twin studies did not account for deaths caused by violence, accidents, infectious diseases, and other factors originating outside the body – termed extrinsic mortality – which the authors of the new study said skewed earlier findings on the genetic component of longevity.

The cause of death was not recorded in the historical data, which only provided the age of death. So, if one twin died at age 90 from natural causes, and another at age 30 not from natural causes, but from an infectious disease like typhoid or cholera, data without the cause of death could give a false impression of the role of heredity in lifespan.

The new study used a mathematical formula to account for extrinsic mortality among twins. Shenhar said that extrinsic mortality at the time the twins studied lived, before the antibiotic era, was 10 times higher than it is today, primarily due to infectious diseases that are now easily treatable.

The scientists then confirmed the prediction that extrinsic deaths mask heritability using previously unanalyzed data and more recent data from Sweden that included twins raised together and twins raised apart. This analysis indeed revealed that as extrinsic mortality falls, heritability rises.

- Identical twins raised apart share their genes but not their environment. This helps to separate genetics from environment, nature from nurture – said Weizmann Institute biologist Uri Alon.

Dizygotic twins are also valuable in such research because they share about half of their genetic makeup.

- Previous twin studies used statistical methods that work well for other traits – height, blood pressure, personality traits, etc. These traits are not affected by extrinsic mortality.

But average lifespan is the only special trait that is strongly affected by extrinsic mortality. Since the cause of death was not recorded in classical twin studies, it was not corrected – Alon said.

Shenhar said that low heritability estimates may have discouraged funding and research into the genetics of aging, suggesting it was largely random or environmental.

- Our work validates the search for genetic factors of longevity, showing that the genetic signal is strong, but it was previously obscured by 'noise' in the data – Shenhar pointed out.

Genes affect lifespan in both directions. On one hand, there are debilitating genetic defects that can cause diseases and shorten lifespan. On the other hand, there are genes that have been identified that seem to offer advantages for longevity.

- Many centenarians live to 100 without any serious health problems. Clearly, these people have protective genes that guard against the development of diseases that naturally occur with age.

Some of these genes have been identified, although, like most complex traits, longevity is likely influenced by hundreds, if not thousands, of genes – Shenhar concluded.