Journal Article

DZNE-2020-06154

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice.

Xie, K. (First author)DZNE* ; Ryan, D. P.DZNE* ; Pearson, B. L.DZNE* ; Henzel, K. S.DZNE* ; Neff, F. ; Vidal, R. O.DZNE* ; Hennion, M.DZNE* ; Lehmann, I.DZNE* ; Schleif, M.DZNE* ; Schröder, S.DZNE* ; Adler, T. ; Rathkolb, B. ; Rozman, J. ; Schütz, A.-L.DZNE* ; Prehn, C. ; Mickael, M. E.DZNE* ; Weiergräber, M. ; Adamski, J. ; Busch, D. H. ; Ehninger, G. ; Matynia, A. ; Jackson, W. S.DZNE* ; Wolf, E. ; Fuchs, H. ; Gailus-Durner, V. ; Bonn, S.DZNE* ; Hrabě de Angelis, M. ; Ehninger, D. (Last author)DZNE*

2018
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1707337115

Abstract: Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice.

Keyword(s): Age Factors (MeSH) ; Aging: genetics (MeSH) ; Aging: physiology (MeSH) ; Animals (MeSH) ; DNA Methylation (MeSH) ; Epigenesis, Genetic (MeSH) ; Fathers (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Life Expectancy (MeSH) ; Longevity (MeSH) ; Male (MeSH) ; Mechanistic Target of Rapamycin Complex 1: genetics (MeSH) ; Mechanistic Target of Rapamycin Complex 1: metabolism (MeSH) ; Mice (MeSH) ; Pedigree (MeSH) ; Promoter Regions, Genetic (MeSH) ; Spermatozoa: metabolism (MeSH) ; Mechanistic Target of Rapamycin Complex 1

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Contributing Institute(s):

1. Molecular and Cellular Cognition (AG Ehninger)
2. Computational analysis of biological networks (AG Bonn 1)
3. Selective Vulnerability of Neurodegenerative Diseases (AG Jackson)
4. Animal Facility Bonn (Animal Facility Bonn)
5. RNAome database (RNAome database)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; National-Konsortium ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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