MedicalResearch.com Interview with:
Dr. Zoltán Kutalik, PhD
Swiss Institute of Bioinformatics
Assistant professor at the Institute of Social and Preventive Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Why do some of us live longer than others? While the environment in which we live – including our socio-economic status or the food we eat – plays the biggest part, about 20 to 30% of 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. Until now, the most comprehensive studies had found only two hits in the genome.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: An unparalleled number of SNPs associated with lifespan (16) were uncovered, including 14 new to science. In our approach, we prioritized changes in the DNA known to be linked to age-related diseases in order to scan the genome more efficiently.
About 1 in 10 people carry some configurations of these markers that shorten their life by over a year compared with the population average. In addition, a person inheriting a lifespan-shortening version of one of these SNPs may die up to seven months earlier.
The approach also enabled us to explore how the DNA changes affected lifespan in a holistic way. We 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.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Our findings reveal shared molecular mechanisms between human and model organisms, which will be explored in more depth in the future.
MedicalResearch.com: Is there anything else you would like to add?
Response: The discovered SNPs, combined with gene expression data, allowed us to identify that lower brain expression of three genes neighbouring the SNPs (RBM6, SULT1A1 and CHRNA5) 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. Drugs targeting these biomarkers in the future may lead to improved human lifespan.
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Aaron F. McDaid, Peter K. Joshi, Eleonora Porcu, Andrea Komljenovic, Hao Li, Vincenzo Sorrentino, Maria Litovchenko, Roel P. J. Bevers, Sina Rüeger, Alexandre Reymond, Murielle Bochud, Bart Deplancke, Robert W. Williams, Marc Robinson-Rechavi, Fred Paccaud, Valentin Rousson, Johan Auwerx, James F. Wilson, Zoltán Kutalik. Bayesian association scan reveals loci associated with human lifespan and linked biomarkers. Nature Communications, 2017; 8: 15842 DOI: 10.1038/NCOMMS15842
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