Genes contribute far more of a person’s lifespan than previously believed, a study in twins has revealed.
The research, in Science, counters prevalent views that longevity is largely influenced by external forces such as environmental factors and lifestyle.
The findings revealed that more than half of the human lifespan is inherited, with different diseases passed down to different degrees through the generations.
The researchers suggest earlier studies may have failed to adequately account for the impact of external hazards such as accidents or infections.
Commenting in a related Perspective article, Daniela Bakula, PhD, and Morten Scheibye-Knudsen, PhD, from the University of Copenhagen, said the findings have important consequences for aging research.
“A substantial genetic contribution strengthens the rationale for large-scale efforts to identify longevity-associated variants, refine polygenic risk scores, and link genetic differences to specific biological pathways that regulate aging,” they explained.
Previous twin studies have suggested that around a fifth to a quarter of a person’s lifespan is inherited, with other investigations suggesting this could be as low as six percent.
That research has contributed to growing skepticism over the role of genetics in aging and cast doubt over the feasibility of identifying genetic determinants of longevity.
However, most lifespan studies involved people born in the 18th and 19th centuries when there were appreciable rates of extrinsic mortality, caused by factors originating outside the body such as accidents, homicides, infectious diseases, and environmental hazards.
Using mathematical modeling and simulations, Uri Alon, PhD, from the Weizmann Institute of Science in Rehovot, Israel, and team attempted to correct for this and the cutoff age—the minimum age at which participants must be alive to be included in a study.
They initially used two human mortality models, separating the intrinsic and extrinsic components, before testing their conclusions on data from three studies of twins that had been raised together and apart.
Results revealed that heritability of the human lifespan due to intrinsic mortality was 55%, more than doubling previous estimates.
Interestingly, the risk of different diseases being passed on through generations differed for different diseases, with cardiovascular disease and dementia showing higher heritability than cancer.
“The key insight is that extrinsic mortality systematically masked the genetic contribution to lifespan in traditional analyses,” the authors reported.
They added: “Identifying the genetic variants underlying this heritability would help us to understand the fundamental mechanisms of human aging.”
Bakula and Scheibye-Knudsen further noted: “If lifespan is largely fixed by genetics, then the scope for influencing the rate of aging is limited, particularly for lifestyle interventions.
“Conversely, if genetic contributions are minimal, efforts to understand aging through genetic approaches are difficult to justify.
“Clarifying the role of inherited variation in aging-related mortality is therefore central to both biological understanding and societal expectations.”
