It is common knowledge that the answer to why some of us live longer than the others is embedded in our genome.
Swiss scientists from the SIB Swiss Institute of Bioinformatics, the Lausanne University Hospital (CHUV), the University of Lausanne and the EPFL, have now identified 16 genetic markers associated with a decreased lifespan, including 14 new to science.
While our environment including our socio-economic status or the food we eat, plays a big part- about 20 to 30%- in the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity.
The study appearing in Nature Communications details the use of an innovative computational approach to analyse a dataset of 116,279 individuals and probe 2.3 million human SNPs. The approach prioritised changes in the DNA known to be linked to age-related diseases in order to scan the genome more efficiently.
“This is the largest set of lifespan-associated genetic markers ever uncovered.” Says senior study investigator Zoltán Kutalik, Ph.D., group leader at SIB and assistant professor at the Institute of Social and Preventive Medicine (CHUV).
According to the study, about
1 in 10 people carry some configurations of these markers that shorten their life by over a year compared with the population average. Moreover, the researchers found that a person inheriting a lifespan-shortening version of one of these SNPs may die up to seven months earlier.“…we developed a Mendelian randomization-based method combining 58 disease-related GWA [genome-wide association] studies to derive longevity priors for all HapMap SNPs,” the authors wrote. “A Bayesian association scan, informed by these priors, for parental age of death in the UK Biobank study (n=116,279) revealed 16 independent SNPs with significant Bayes factor at a 5% false discovery rate (FDR). Eleven of them replicate (5% FDR) in five independent longevity studies combined; all but three are depleted of the life-shortening alleles in older Biobank participants.”
The approach enabled the researchers to explore how the DNA changes affected lifespan in a holistic way. They found that most SNPs had an effect on lifespan by impacting more than a single disease or risk factor, for example through being more addicted to smoking as well as through being predisposed to schizophrenia.
The discovered SNPs, combined with gene expression data, allowed the researchers to identify that lower brain expression of three genes neighbouring the SNPs (RBM6, SULT1A1 and CHRNA5, involved in nicotine dependence) was causally linked to increased lifespan.
These three genes could therefore act as biomarkers of longevity, i.e. survival beyond 85-100 years. “To support this hypothesis, we have shown that mice with a lower brain expression level of RBM6 lived substantially longer,” comments Prof. Johan Auwerx, professor at the EPFL.
Study co-author Marc Robinson-Rechavi, Ph.D., a SIB group leader, and professor at the University of Lausanne, concluded that “interestingly, the gene expression impact of some of these SNPs in humans is analogous to the consequence of a low-calorie diet in mice, which is known to have positive effects on lifespan.”
