The impact of the cardiovascular component and somatic mutations on ageing

Author:

Garger Daniel12,Meinel Martin123,Dietl Tamina12,Hillig Christina14,Garzorz‐Stark Natalie35,Eyerich Kilian56,de Angelis Martin Hrabě789,Eyerich Stefanie1011,Menden Michael P.12912ORCID

Affiliation:

1. Computational Health Center, Helmholtz Munich Neuherberg Germany

2. Faculty of Biology Ludwig Maximilian University Martinsried Germany

3. Department of Dermatology and Allergy Technical University of Munich Munich Germany

4. Department of Mathematics Technical University of Munich Munich Germany

5. Division of Dermatology and Venereology, Department of Medicine Solna, and Center for molecular medicine Karolinska Institutet Stockholm Sweden

6. Department of Dermatology and Venerology, Medical School University of Freiburg Freiburg Germany

7. Institute of Experimental Genetics Helmholtz Munich Neuherberg Germany

8. Chair of Experimental Genetics, TUM School of Life Sciences Technical University Munich Freising Germany

9. German Center for Diabetes Research (DZD) Neuherberg Germany

10. Center for Allergy and Environment (ZAUM) Technical University Munich Munich Germany

11. Institute for Allergy Research Helmholtz Munich, Neuherberg Neuherberg Germany

12. Department of Biochemistry and Pharmacology University of Melbourne Parkville Victoria Australia

Abstract

AbstractMechanistic insight into ageing may empower prolonging the lifespan of humans; however, a complete understanding of this process is still lacking despite a plethora of ageing theories. In order to address this, we investigated the association of lifespan with eight phenotypic traits, that is, litter size, body mass, female and male sexual maturity, somatic mutation, heart, respiratory, and metabolic rate. In support of the somatic mutation theory, we analysed 15 mammalian species and their whole‐genome sequencing deriving somatic mutation rate, which displayed the strongest negative correlation with lifespan. All remaining phenotypic traits showed almost equivalent strong associations across this mammalian cohort, however, resting heart rate explained additional variance in lifespan. Integrating somatic mutation and resting heart rate boosted the prediction of lifespan, thus highlighting that resting heart rate may either directly influence lifespan, or represents an epiphenomenon for additional lower‐level mechanisms, for example, metabolic rate, that are associated with lifespan.

Publisher

Wiley

Subject

Cell Biology,Aging

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