Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice

• DOI: 10.1073/pnas.1707337115
• Publication Date: 2018-02-21T20:25:27Z
• Authors: Kan Xie; Devon P. Ryan; Brandon L. Pearson; Kristin S. Henzel; Frauke Neff; Ramon O. Vidal; Magali Hennion; Isabelle Lehmann; Melvin Schleif; Susanne Schröder; Thure Adler; Birgit Rathkolb; Jan Rozman; Anna-Lena Schütz; Cornelia Prehn; Michel E. Mickael; Marco Weiergräber; Jerzy Adamski; Dirk H. Busch; Gerhard Ehninger; Anna Matynia; Walker S. Jackson; Eckhard Wolf; Helmut Fuchs; Valerie Gailus-Du...; Stefan Bonn; Martin Hrabě de A...; Dan Ehninger
• Keywords: Life span; Epigenesis; Senescence; Population Ageing

Significance Aging-associated diseases are increasingly common in an aging global population. However, the contributors and origins of differential risk for unhealthy remain poorly understood. Using a mouse model, we found that offspring aged fathers exhibited reduced life span more pronounced aging-associated pathologies than animals sired by young fathers. Tissue revealed shared epigenetic signatures showed altered activation states longevity-related cell signaling. Our results suggest variability trajectories could derive, part, from age at conception father, possibility warrants human epidemiological investigation.