Parental lifespan genes could pave way for new therapeutic targets to prolong life

A large-scale international study led by the University of Exeter Medical School has discovered new genes linked to parents' lifespan - which could one day be targeted to help prolong human life.

How long we live is determined by a range of factors including our lifestyle and how well we treat factors including blood pressure and cholesterol from midlife. However, genetics, and how long our parental relatives lived, also plays a role. Now, the number of genes we know influence lifespan has expanded, potentially paving the way to new therapeutic targets to prolong life.

The study was funded by the Medical Research Council and conducted in collaboration with a number of US universities, undertook a genome-wide search for variants influencing how long participants' parents lived. The team studied 389,166 volunteers who took part in the UK Biobank, with confirmation in the US Health and Retirement Study and the Wisconsin Longitudinal Study. The DNA samples from the volunteers carry the genetics of their biological parents, so provide a practical way of studying exceptionally long lifespans.

Eight genetic variants had already been linked for lifespan, mainly involved in heart disease and dementia. The latest study, published in the journal Aging NY, has expanded this to 25 genes in all, with some specific to mothers' or fathers' lifespan separately.

Dr Luke Pilling, who undertook most of analyses said: "We have identified new pathways that contribute to survival, as well as confirming others. These targets, including inflammatory and cardiovascular pathways, offer potentially modifiable targets to reduce risk of an earlier death and improve health."

Genes involved in senescence, the 'frozen' state that cells enter into after being damaged, played an important role in longevity. Drugs targeting senescence have already been shown to extend life in laboratory animals.

Genes related to inflammation and auto-immunity related genes were also prominent, opening up the possibility that precision anti-inflammatory treatments may one day be helpful in extending life.

The results confirm that many genetic variants combine to influence human lifespan: no single gene variant was found to be responsible. The study found evidence to suggest that the genetic variants for average lifespan also influence exceptionally long life expectancy. A genetic risk score combining the top ten variants was statistically associated with parents being centenarians.

Professor David Melzer, of the University of Exeter Medical School, who led the group said: "This study help open the way to novel treatment, but the strong role for genes affecting heart disease risk again underlines the importance of controlling blood pressure and cholesterol levels throughout the lifespan. Of course, adopting healthy lifestyles is important, and can probably overcome the negative effects of most of the genes found so far."

Dr. George Kuchel, Professor of Geriatrics at University of Connecticut School of Medicine and Director of the UConn Center on Aging said, "These findings extend the number of genetic markers now shown to be associated with exceptional longevity. However, even more importantly they add to a growing body of knowledge highlighting specific targets and biological pathways useful for the development of interventions designed to help maintain health, function and independence in later life."