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

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Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice. / Xie, Kan; Ryan, Devon P; Pearson, Brandon L; Henzel, Kristin S; Neff, Frauke; Vidal, Ramon O; Hennion, Magali; Lehmann, Isabelle; Schleif, Melvin; Schröder, Susanne; Adler, Thure; Rathkolb, Birgit; Rozman, Jan; Schütz, Anna-Lena; Prehn, Cornelia; Mickael, Michel E; Weiergräber, Marco; Adamski, Jerzy; Busch, Dirk H; Ehninger, Gerhard; Matynia, Anna; Jackson, Walker S; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; Bonn, Stefan; Hrabě de Angelis, Martin; Ehninger, Dan.

in: P NATL ACAD SCI USA, Jahrgang 115, Nr. 10, 06.03.2018, S. E2348-E2357.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Xie, K, Ryan, DP, Pearson, BL, Henzel, KS, Neff, F, Vidal, RO, Hennion, M, Lehmann, I, Schleif, M, Schröder, S, Adler, T, Rathkolb, B, Rozman, J, Schütz, A-L, Prehn, C, Mickael, ME, Weiergräber, M, Adamski, J, Busch, DH, Ehninger, G, Matynia, A, Jackson, WS, Wolf, E, Fuchs, H, Gailus-Durner, V, Bonn, S, Hrabě de Angelis, M & Ehninger, D 2018, 'Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice', P NATL ACAD SCI USA, Jg. 115, Nr. 10, S. E2348-E2357. https://doi.org/10.1073/pnas.1707337115

APA

Xie, K., Ryan, D. P., Pearson, B. L., Henzel, K. S., Neff, F., Vidal, R. O., Hennion, M., Lehmann, I., Schleif, M., Schröder, S., Adler, T., Rathkolb, B., Rozman, J., Schütz, A-L., Prehn, C., Mickael, M. E., Weiergräber, M., Adamski, J., Busch, D. H., ... Ehninger, D. (2018). Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice. P NATL ACAD SCI USA, 115(10), E2348-E2357. https://doi.org/10.1073/pnas.1707337115

Vancouver

Xie K, Ryan DP, Pearson BL, Henzel KS, Neff F, Vidal RO et al. Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice. P NATL ACAD SCI USA. 2018 Mär 6;115(10):E2348-E2357. https://doi.org/10.1073/pnas.1707337115

Bibtex

@article{aaaa3b9d261b420fb2f32ac686dcde75,
title = "Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice",
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.",
keywords = "Age Factors, Aging, Animals, DNA Methylation, Epigenesis, Genetic, Fathers, Female, Humans, Life Expectancy, Longevity, Male, Mechanistic Target of Rapamycin Complex 1, Mice, Pedigree, Promoter Regions, Genetic, Spermatozoa, Journal Article, Research Support, Non-U.S. Gov't",
author = "Kan Xie and Ryan, {Devon P} and Pearson, {Brandon L} and Henzel, {Kristin S} and Frauke Neff and Vidal, {Ramon O} and Magali Hennion and Isabelle Lehmann and Melvin Schleif and Susanne Schr{\"o}der and Thure Adler and Birgit Rathkolb and Jan Rozman and Anna-Lena Sch{\"u}tz and Cornelia Prehn and Mickael, {Michel E} and Marco Weiergr{\"a}ber and Jerzy Adamski and Busch, {Dirk H} and Gerhard Ehninger and Anna Matynia and Jackson, {Walker S} and Eckhard Wolf and Helmut Fuchs and Valerie Gailus-Durner and Stefan Bonn and {Hrab{\v e} de Angelis}, Martin and Dan Ehninger",
note = "Copyright {\textcopyright} 2018 the Author(s). Published by PNAS.",
year = "2018",
month = mar,
day = "6",
doi = "10.1073/pnas.1707337115",
language = "English",
volume = "115",
pages = "E2348--E2357",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "10",

}

RIS

TY - JOUR

T1 - Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice

AU - Xie, Kan

AU - Ryan, Devon P

AU - Pearson, Brandon L

AU - Henzel, Kristin S

AU - Neff, Frauke

AU - Vidal, Ramon O

AU - Hennion, Magali

AU - Lehmann, Isabelle

AU - Schleif, Melvin

AU - Schröder, Susanne

AU - Adler, Thure

AU - Rathkolb, Birgit

AU - Rozman, Jan

AU - Schütz, Anna-Lena

AU - Prehn, Cornelia

AU - Mickael, Michel E

AU - Weiergräber, Marco

AU - Adamski, Jerzy

AU - Busch, Dirk H

AU - Ehninger, Gerhard

AU - Matynia, Anna

AU - Jackson, Walker S

AU - Wolf, Eckhard

AU - Fuchs, Helmut

AU - Gailus-Durner, Valerie

AU - Bonn, Stefan

AU - Hrabě de Angelis, Martin

AU - Ehninger, Dan

N1 - Copyright © 2018 the Author(s). Published by PNAS.

PY - 2018/3/6

Y1 - 2018/3/6

N2 - 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.

AB - 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.

KW - Age Factors

KW - Aging

KW - Animals

KW - DNA Methylation

KW - Epigenesis, Genetic

KW - Fathers

KW - Female

KW - Humans

KW - Life Expectancy

KW - Longevity

KW - Male

KW - Mechanistic Target of Rapamycin Complex 1

KW - Mice

KW - Pedigree

KW - Promoter Regions, Genetic

KW - Spermatozoa

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1073/pnas.1707337115

DO - 10.1073/pnas.1707337115

M3 - SCORING: Journal article

C2 - 29467291

VL - 115

SP - E2348-E2357

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 10

ER -