Ageing as a software design flaw.
Antagonistic pleiotropy
Genome
Information theory
Longevity
Programmed ageing
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
28 03 2023
28 03 2023
Historique:
received:
19
10
2022
accepted:
27
02
2023
medline:
29
3
2023
entrez:
27
3
2023
pubmed:
28
3
2023
Statut:
epublish
Résumé
Ageing is inherent to all human beings, yet why we age remains a hotly contested topic. Most mechanistic explanations of ageing posit that ageing is caused by the accumulation of one or more forms of molecular damage. Here, I propose that we age not because of inevitable damage to the hardware but rather because of intrinsic design flaws in the software, defined as the DNA code that orchestrates how a single cell develops into an adult organism. As the developmental software runs, its sequence of events is reflected in shifting cellular epigenetic states. Overall, I suggest that to understand ageing we need to decode our software and the flow of epigenetic information throughout the life course.
Identifiants
pubmed: 36973715
doi: 10.1186/s13059-023-02888-y
pii: 10.1186/s13059-023-02888-y
pmc: PMC10042583
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
51Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R014949/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 208375/Z/17/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/V010123/1
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
Références
Nat Rev Genet. 2018 Jun;19(6):371-384
pubmed: 29643443
Aging (Albany NY). 2018 Apr 18;10(4):573-591
pubmed: 29676998
Nat Rev Mol Cell Biol. 2015 Oct;16(10):593-610
pubmed: 26373265
Mol Psychiatry. 2023 Jan;28(1):242-255
pubmed: 35840801
Mech Ageing Dev. 1984 Nov;28(1):23-40
pubmed: 6542614
Nature. 2010 Mar 25;464(7288):504-12
pubmed: 20336132
Rejuvenation Res. 2012 Oct;15(5):483-94
pubmed: 23098078
Nat Commun. 2020 Mar 24;11(1):1545
pubmed: 32210226
Aging Cell. 2019 Feb;18(1):e12877
pubmed: 30450724
Dermatol Clin. 1993 Oct;11(4):749-57
pubmed: 8222358
Nature. 2020 Dec;588(7836):124-129
pubmed: 33268865
Aging Cell. 2010 Feb;9(1):92-5
pubmed: 19878144
Curr Biol. 2011 Sep 27;21(18):R701-7
pubmed: 21959160
Semin Cell Dev Biol. 2006 Aug;17(4):492-502
pubmed: 16807002
Nat Commun. 2021 Mar 12;12(1):1615
pubmed: 33712580
Genome Res. 2010 Sep;20(9):1207-18
pubmed: 20647238
Nature. 2023 Jan;613(7944):550-557
pubmed: 36599986
Nat Commun. 2022 Nov 11;13(1):6830
pubmed: 36369285
Nat Cell Biol. 2019 Jan;21(1):63-71
pubmed: 30602761
Cell. 2023 Jan 19;186(2):243-278
pubmed: 36599349
Exp Biol Med (Maywood). 2020 Nov;245(17):1532-1542
pubmed: 32276545
Cell. 2014 Nov 6;159(4):709-13
pubmed: 25417146
Dev Genet. 1996;18(2):173-9
pubmed: 8934879
Acta Clin Croat. 2020 Dec;59(4):650-660
pubmed: 34456453
Science. 1998 Jan 16;279(5349):349-52
pubmed: 9454332
Biol Bull. 1996 Jun;190(3):302-312
pubmed: 29227703
Ageing Res Rev. 2020 Jul;60:101050
pubmed: 32272169
Mech Ageing Dev. 2021 Dec;200:111583
pubmed: 34637937
Mech Ageing Dev. 2011 Jan-Feb;132(1-2):65-71
pubmed: 21184773
Mol Oncol. 2022 Sep;16(18):3238-3258
pubmed: 35726685
Bioessays. 2008 Jun;30(6):567-78
pubmed: 18478536
Biochim Biophys Acta. 2008 Jul;1783(7):1280-5
pubmed: 18445486
Aging Cell. 2011 Oct;10(5):761-8
pubmed: 21518243
Trends Endocrinol Metab. 2022 Apr;33(4):266-280
pubmed: 35183431
Q Rev Biol. 1976 Mar;51(1):49-83
pubmed: 6991
Trends Cancer. 2022 Nov;8(11):962-971
pubmed: 35811230
Nat Commun. 2014 Jun 24;5:4222
pubmed: 24957317
Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R47-58
pubmed: 15809273
Blood. 2022 Apr 28;139(17):2653-2665
pubmed: 35231105
J Gerontol A Biol Sci Med Sci. 2007 Feb;62(2):149-60
pubmed: 17339640
Biochemistry (Mosc). 2014 Oct;79(10):977-93
pubmed: 25519058
Biochem Biophys Res Commun. 2020 May 7;525(3):563-569
pubmed: 32115145
Clin Epigenetics. 2021 Sep 6;13(1):170
pubmed: 34488874
Cell Cycle. 2006 Sep;5(18):2087-102
pubmed: 17012837
FASEB J. 2012 Dec;26(12):4821-6
pubmed: 22964300
Nat Rev Genet. 2005 Nov;6(11):866-72
pubmed: 16304601
Exp Gerontol. 2017 Aug;94:41-45
pubmed: 27956088
Genome Res. 2010 Apr;20(4):434-9
pubmed: 20219945
Sci Adv. 2022 Sep 16;8(37):eabo5482
pubmed: 36112674
J Cell Biol. 2019 Jan 7;218(1):70-82
pubmed: 30257850
Proc Nutr Soc. 2006 Feb;65(1):97-105
pubmed: 16441949
Trends Biotechnol. 2022 Jun;40(6):639-642
pubmed: 35190201
Cell. 2016 Dec 15;167(7):1719-1733.e12
pubmed: 27984723
Prog Retin Eye Res. 2005 May;24(3):379-93
pubmed: 15708834
Regen Med. 2019 Sep;14(9):867-886
pubmed: 31455183
Nature. 2022 Apr;604(7906):517-524
pubmed: 35418684
Science. 1990 Apr 20;248(4953):356-8
pubmed: 17784491
Proc Natl Acad Sci U S A. 1917 May;3(5):382-6
pubmed: 16586742
Cell. 2023 Jan 19;186(2):305-326.e27
pubmed: 36638792
Nature. 2018 Sep;561(7721):45-56
pubmed: 30185958
Cell Mol Life Sci. 2022 Aug 20;79(9):489
pubmed: 35987825
Nucleic Acids Res. 2018 Jan 4;46(D1):D1083-D1090
pubmed: 29121237
Genome Biol. 2015 Jan 30;16:25
pubmed: 25633388
Aging (Albany NY). 2016 Sep 28;8(9):1844-1865
pubmed: 27690265
Genes (Basel). 2021 Apr 21;12(5):
pubmed: 33919082
Nature. 2016 Dec 1;540(7631):119-123
pubmed: 27880763
Aging Cell. 2010 Feb;9(1):54-63
pubmed: 19895632
Pharmacol Rev. 2012 Jan;64(1):88-101
pubmed: 22090473
Ann N Y Acad Sci. 2007 Apr;1100:1-13
pubmed: 17460161
Nature. 2000 Nov 9;408(6809):233-8
pubmed: 11089980
Nature. 1976 Apr 8;260(5551):523-5
pubmed: 1264206
Cell Cycle. 2010 May 15;9(10):1859-62
pubmed: 20436272
Biochemistry (Mosc). 2014 Oct;79(10):1032-48
pubmed: 25519062
Nature. 2022 May;605(7909):325-331
pubmed: 35418683
Biochemistry (Mosc). 2012 Jul;77(7):689-706
pubmed: 22817532
Physiology (Bethesda). 2005 Aug;20:252-9
pubmed: 16024513
Ageing Res Rev. 2022 Feb;74:101557
pubmed: 34990845
Nat Aging. 2021 Dec;1(12):1096-1106
pubmed: 36846190
Int J Mol Sci. 2020 Jan 22;21(3):
pubmed: 31979100
Nat Rev Genet. 2022 Oct;23(10):585-605
pubmed: 35501397
Biogerontology. 2015 Aug;16(4):383-97
pubmed: 25832892
Heredity (Edinb). 1993 Jul;71 ( Pt 1):23-32
pubmed: 8360076
Nat Rev Cancer. 2013 May;13(5):357-65
pubmed: 23612461
Front Cell Dev Biol. 2021 Aug 27;9:688788
pubmed: 34513830
Development. 2019 Jul 22;146(14):
pubmed: 31332037
EMBO Rep. 2022 Sep 5;23(9):e55299
pubmed: 35796299
Genetics. 2018 Apr;208(4):1617-1630
pubmed: 29444805
Mech Ageing Dev. 2005 Oct;126(10):1026-33
pubmed: 15946728
Crit Rev Biochem Mol Biol. 2019 Feb;54(1):61-83
pubmed: 30822165
Genes Dev. 2014 Apr 15;28(8):812-28
pubmed: 24736841
Nature. 2013 Oct 17;502(7471):340-5
pubmed: 24025773
Ageing Res Rev. 2021 Jul;68:101316
pubmed: 33711511
Mech Ageing Dev. 2010 Oct;131(10):641-9
pubmed: 20816690
Exp Gerontol. 2002 Jun;37(6):769-75
pubmed: 12175477
Proc Biol Sci. 2021 Feb 10;288(1944):20201728
pubmed: 33529563
Biogerontology. 2003;4(2):119-20
pubmed: 12766537
Nature. 2021 Jun;594(7862):271-276
pubmed: 33910229
Nat Struct Mol Biol. 2013 Mar;20(3):274-81
pubmed: 23463312
Genome Biol. 2013;14(10):R115
pubmed: 24138928
J Gerontol A Biol Sci Med Sci. 1999 Jul;54(7):B297-307
pubmed: 10462163
Mutat Res. 2011 Jul-Oct;728(1-2):12-22
pubmed: 21600302
Sci Adv. 2021 Jun 25;7(26):
pubmed: 34172448
Ageing Res Rev. 2021 Sep;70:101407
pubmed: 34271186
Hum Mol Genet. 2016 Nov 1;25(21):4804-4818
pubmed: 28175300
Biol Rev Camb Philos Soc. 2018 Aug;93(3):1715-1734
pubmed: 29663630
Immunol Today. 1996 Jun;17(6):267-72
pubmed: 8962629
Nat Genet. 2004 Feb;36(2):197-204
pubmed: 14730301
Nat Commun. 2021 Oct 5;12(1):5801
pubmed: 34611154