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

Proceedings of the National Academy of Sciences of the United States of America
Kan XieDan Ehninger

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 fin...Continue Reading

References

Sep 21, 1979·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·T B Kirkwood, R Holliday
Jul 12, 1996·Cell·L Guarente
Jul 4, 1997·Science·L A Gavrilov, N S Gavrilova
Aug 1, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R A MillerA Galecki
Apr 25, 2001·Archives of General Psychiatry·D MalaspinaE S Susser
May 23, 2002·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Erin L ManningGary Van Zant
Sep 27, 2005·The Journal of Biological Chemistry·Dos D Sarbassov, David M Sabatini
Sep 16, 2006·Journal of Epidemiology and Community Health·Isabelle BrayGeorge Davey Smith
Feb 3, 2007·BioTechniques·Michael R LamprechtAnne E Carpenter
Jul 14, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Levy KopelovichJames A Crowell
Jul 14, 2007·FEBS Letters·Kazutetsu Aoshiba, Atsushi Nagai
Jan 29, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Hélène BulckaenFrançois Puisieux
Jun 24, 2008·Nature Medicine·Dan EhningerAlcino J Silva
Jul 11, 2008·Kidney International·Xin J ZhouFred G Silva
Oct 17, 2008·Biology of Reproduction·Silvia García-PalomaresJuan J Tarín
Jan 24, 2009·Biology of Reproduction·Jonathan A SchmidtRalph L Brinster
Feb 5, 2009·Bioinformatics·João Pedro de MagalhãesGeorge M Church
May 20, 2009·Circulation·Dao-Fu DaiPeter S Rabinovitch
Jul 10, 2009·Nature·David E HarrisonRichard A Miller
Aug 5, 2009·Clinical Reviews in Allergy & Immunology·Annabelle Grolleau-JuliusRaymond L Yung
May 18, 2010·Nature Structural & Molecular Biology·Urszula BrykczynskaAntoine H F M Peters
Jul 14, 2010·Hormones and Behavior·James P CurleyFrances A Champagne
Jul 22, 2010·Development, Growth & Differentiation·Hirofumi Furuhashi, William G Kelly
Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Beatrice T WangKevan M Shokat
Oct 19, 2011·Cytokine·Isobel R GowersAnthony G Wilson
Oct 29, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Yang SongDaniel R Goldstein
Jun 13, 2012·Proceedings of the National Academy of Sciences of the United States of America·Holger HeynManel Esteller
Oct 18, 2012·American Journal of Human Biology : the Official Journal of the Human Biology Council·Willy EriksenKristian Tambs
Dec 12, 2012·Molecular Cell·Stefanie SeisenbergerWolf Reik
May 24, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ali B RodgersTracy L Bale
Jun 12, 2013·Nature Reviews. Genetics·Z Jeffrey Chen
Jul 19, 2013·The Journal of Clinical Investigation·Frauke NeffDan Ehninger
Aug 21, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Oluwatosin TaiwoDaniel J Pearce

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Citations

Sep 28, 2018·Genes, Brain, and Behavior·Claire J FoldiThomas H J Burne
Jan 23, 2019·Reproduction : the Official Journal of the Society for the Study of Fertility·Jonathan P EvansFrancisco Garcia-Gonzalez
May 28, 2019·Current Diabetes Reports·Lei Su, Mary Elizabeth Patti
Jun 5, 2019·Nutrients·Agnieszka Gadecka, Anna Bielak-Zmijewska
Dec 19, 2019·Proceedings. Biological Sciences·Pat Monaghan, Neil B Metcalfe
Jan 10, 2020·Nature Protocols·I BellantuonoD W Lamming
Feb 6, 2020·Nature Reviews. Molecular Cell Biology·Weiqi ZhangJuan Carlos Izpisua Belmonte
Jul 12, 2019·PloS One·Takashi SakamotoTakefumi Kikusui
Aug 1, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Britt J Heidinger, Rebecca C Young
Jul 30, 2020·Stem Cells International·Shuang Jiang, Yuchen Guo
Apr 7, 2020·The Journal of Animal Ecology·Foteini Spagopoulou
Mar 21, 2020·Frontiers in Cell and Developmental Biology·Yoyo Chih-Yun YuShau-Ping Lin
Jul 19, 2019·F1000Research·David PapadopoliLaura Hulea
Oct 12, 2018·Oxidative Medicine and Cellular Longevity·Arun SamiduraiAnindita Das
Nov 10, 2020·Human Reproduction·Jolien Van OpstalAdelheid Soubry
Nov 11, 2020·Journal of Assisted Reproduction and Genetics·Stanislav A VasilyevIgor N Lebedev
Nov 29, 2020·BMC Biology·Joanna RutkowskaShinichi Nakagawa
Jan 6, 2021·EMBO Reports·Kaichi YoshizakiNoriko Osumi
Feb 11, 2021·Ecology Letters·Pauline VuarinGabriele Sorci
Feb 9, 2021·British Journal of Pharmacology·Shuoshuo LiZengqiang Yuan
Nov 14, 2020·Reproductive Biology and Endocrinology : RB&E·Iman HalvaeiNavid Esfandiari

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Methods Mentioned

BETA
RNA-seq
ChIP-seq
RRBS
FACS
protein assay
electrophoresis

Software Mentioned

ilastik
GraphPad Prism
CellProfiler
ImageJ
R

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