title: Natural selection of mitochondria during somatic lifetime promotes healthy aging.
abstract: Stimulation of mitochondrial biogenesis during life-time challenges both eliminates disadvantageous properties and drives adaptive selection of advantageous phenotypic variations. Intermittent fission and fusion of mitochondria provide specific targets for health promotion by brief temporal stressors, interspersed with periods of recovery and biogenesis. For mitochondria, the mechanisms of selection, variability, and heritability, are complicated by interaction of two independent genomes, including the multiple copies of DNA in each mitochondrion, as well as the shared nuclear genome of each cell. The mechanisms of stress-induced fission, followed by recovery-induced fusion and biogenesis, drive the improvement of mitochondrial functions, not only as directed by genotypic variations, but also as enabled by phenotypic diversity. Selective adaptation may explain unresolved aspects of aging, including the health effects of exercise, hypoxic and poisonous preconditioning, and tissue-specific mitochondrial differences. We propose that intermittent purposeful enhancement of mitochondrial biogenesis by stressful episodes with subsequent recovery paradoxically promotes adaptive mitochondrial health and continued healthy aging.
authors: Department of Nuclear Medicine & PET Centre, Aarhus University Hospital Aarhus, Denmark.
authors: Anders
authors: A
authors: Rodell
authors: Lene J
authors: LJ
authors: Rasmussen
authors: Linda H
authors: LH
authors: Bergersen
authors: Keshav K
authors: KK
authors: Singh
authors: Albert
authors: A
authors: Gjedde
keywords: energy metabolism; epigenetics; evolutionary bottleneck; mitochondrial adaptation; mitochondrial maladaptation
references: Nature. 2010 Mar 25;464(7288):610-4
references: 20200521
references: Exp Neurol. 2013 Sep;247:392-401
references: 23333568
references: Cell. 2012 Oct 12;151(2):333-343
references: 23063123
references: Bioessays. 2011 Nov;33(11):860-9
references: 21922504
references: J Cereb Blood Flow Metab. 2013 Aug;33(8):1307-11
references: 23736643
references: Exp Gerontol. 2008 Sep;43(9):813-9
references: 18662766
references: J Biol Chem. 2006 Dec 8;281(49):37972-9
references: 17003040
references: Exp Cell Res. 2013 Jul 15;319(12):1697-1705
references: 23603281
references: Nucleic Acids Res. 1999 Jun 1;27(11):2434-41
references: 10325435
references: Nat Rev Genet. 2013 Mar;14(3):228-35
references: 23416892
references: Nat Genet. 2004 Nov;36(11):1153-8
references: 15514669
references: Mitochondrion. 2013 Jul;13(4):282-91
references: 23542163
references: Hum Mol Genet. 2013 Jan 15;22(2):384-90
references: 23077218
references: EMBO J. 2008 Jan 23;27(2):433-46
references: 18200046
references: Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10237-42
references: 21646529
references: Nature. 1998 Jan 29;391(6666):441-2
references: 9461208
references: Proc Natl Acad Sci U S A. 1955 Nov 15;41(11):849-57
references: 16589759
references: Trends Neurosci. 2013 Jun;36(6):325-35
references: 23582339
references: Commun Integr Biol. 2011 Sep;4(5):627-9
references: 22046482
references: Brain Dev. 2013 Sep;35(8):757-61
references: 23414619
references: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12553-8
references: 20616029
references: Am J Physiol Regul Integr Comp Physiol. 2011 Jul;301(1):R67-75
references: 21543634
references: Cereb Cortex. 2014 Oct;24(10):2784-95
references: 23696276
references: Ann N Y Acad Sci. 2008 Dec;1147:283-92
references: 19076450
references: Am J Physiol. 1998 May;274(5):R1376-83
references: 9612405
references: Biol Chem. 1999 Jul-Aug;380(7-8):737-47
references: 10494823
references: J Cereb Blood Flow Metab. 2005 Sep;25(9):1183-96
references: 15815583
references: J Physiol. 2009 Jan 15;587(1):285-93
references: 19015195
references: Am J Physiol. 1975 Nov;229(5):1165-9
references: 1200135
references: Biochem Biophys Res Commun. 1982 Aug 31;107(4):1198-205
references: 6291524
references: Antioxid Redox Signal. 2013 Apr 1;18(10):1208-46
references: 22978553
references: Acta Physiol (Oxf). 2010 May;199(1):63-70
references: 20102344
references: Mol Cell Endocrinol. 1998 Oct 25;145(1-2):81-8
references: 9922103
references: Antioxid Redox Signal. 2013 Mar 1;18(7):808-49
references: 22989324
references: Epigenetics. 2012 Apr;7(4):326-34
references: 22419065
references: Nucleic Acids Res. 2001 Nov 1;29(21):4502-8
references: 11691938
references: FASEB J. 2008 Oct;22(10):3443-9
references: 18653766
references: Front Neuroenergetics. 2012 Mar 19;4:5
references: 22457647
references: Cell. 2003 Nov 26;115(5):629-40
references: 14651853
references: BMC Evol Biol. 2008 Feb 18;8:52
references: 18282299
references: Int J Mol Sci. 2009 Apr 24;10(4):1911-29
references: 19468346
references: Cell. 2004 Dec 17;119(6):873-87
references: 15607982
references: Aging Cell. 2005 Oct;4(5):273-83
references: 16164426
references: Nat Rev Genet. 2005 May;6(5):389-402
references: 15861210
references: Am J Hum Genet. 2008 Aug;83(2):254-60
references: 18674747
references: Bioessays. 1999 Jan;21(1):84-8
references: 10070258
references: Exp Brain Res. 2001 Feb;136(4):523-34
references: 11291733
references: J Aging Res. 2012;2012:192503
references: 22720157
references: PLoS Genet. 2012;8(12):e1003148
references: 23284305
references: Cell. 2012 Oct 12;151(2):246-8
references: 23063117
references: Proc Natl Acad Sci U S A. 1982 Mar;79(6):2091-5
references: 6952255
references: Trends Biochem Sci. 2010 Mar;35(3):145-9
references: 20006513
references: Nature. 2001 Feb 22;409(6823):997
references: 11234052
references: J Cereb Blood Flow Metab. 2012 Oct;32(10):1859-68
references: 22781333
references: J Physiol. 2010 Jun 1;588(Pt 11):1985-95
references: 20403976
references: Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4135-40
references: 21368114
references: Antioxid Redox Signal. 2011 May 15;14(10):1939-51
references: 21128700
references: Proc Natl Acad Sci U S A. 1980 Nov;77(11):6715-9
references: 6256757