An energetics perspective on geroscience: mitochondrial protonmotive force and aging.
AMPK
Autophagy
Membrane potential
Metabolism
mTOR
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
16
03
2021
accepted:
07
04
2021
pubmed:
18
4
2021
medline:
29
10
2021
entrez:
17
4
2021
Statut:
ppublish
Résumé
Mitochondria are organelles that provide energy to cells through ATP production. Mitochondrial dysfunction has long been postulated to mediate cellular declines that drive biological aging. Many well-characterized hallmarks of aging may involve underlying energetic defects that stem from loss of mitochondrial function with age. Why and how mitochondrial function declines with age is an open question and one that has been difficult to answer. Mitochondria are powered by an electrochemical gradient across the inner mitochondrial membrane known as the protonmotive force (PMF). This gradient decreases with age in several experimental models. However, it is unclear if a diminished PMF is a cause or a consequence of aging. Herein, we briefly review and define mitochondrial function, we summarize how PMF changes with age in several models, and we highlight recent studies that implicate PMF in aging biology. We also identify barriers that must be addressed for the field to progress. Emerging technology permits more precise in vivo study of mitochondria that will allow better understanding of cause and effect in metabolic models of aging. Once cause and effect can be discerned more precisely, energetics approaches to combat aging may be developed to prevent or reverse functional decline.
Identifiants
pubmed: 33864592
doi: 10.1007/s11357-021-00365-7
pii: 10.1007/s11357-021-00365-7
pmc: PMC8492883
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1591-1604Subventions
Organisme : NIA NIH HHS
ID : P30 AG013280
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS098329
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG066574
Pays : United States
Informations de copyright
© 2021. American Aging Association.
Références
Nature. 2018 Aug;560(7716):102-106
pubmed: 30022159
IDrugs. 2007 Jun;10(6):399-412
pubmed: 17642004
Cell Metab. 2016 Jan 12;23(1):63-76
pubmed: 26674251
J Gerontol. 1956 Jul;11(3):298-300
pubmed: 13332224
Comp Biochem Physiol A Comp Physiol. 1987;88(2):361-7
pubmed: 2890474
Elife. 2020 Mar 17;9:
pubmed: 32180546
Mech Ageing Dev. 2009 Jul;130(7):461-5
pubmed: 19442682
Nat Metab. 2020 Nov;2(11):1316-1331
pubmed: 33139960
Am J Physiol Endocrinol Metab. 2005 Apr;288(4):E674-84
pubmed: 15562252
Antioxid Redox Signal. 2019 Sep 20;31(9):594-607
pubmed: 30887829
CMAJ. 2006 Mar 14;174(6):801-9
pubmed: 16534088
Mech Ageing Dev. 2010 Jul-Aug;131(7-8):463-72
pubmed: 20363244
Development. 2018 Apr 13;145(8):
pubmed: 29654217
J Am Geriatr Soc. 1972 Apr;20(4):145-7
pubmed: 5016631
FEBS J. 2020 Nov;287(21):4544-4556
pubmed: 32459870
Int J Mol Sci. 2017 Apr 28;18(5):
pubmed: 28452964
Science. 2013 Dec 20;342(6165):1524-8
pubmed: 24231806
Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18435-18444
pubmed: 31451640
Cell Metab. 2019 Jan 8;29(1):27-37
pubmed: 30503034
Nat Commun. 2013;4:2192
pubmed: 23900241
Elife. 2019 Aug 14;8:
pubmed: 31411562
Cell. 2013 Jun 6;153(6):1194-217
pubmed: 23746838
Nature. 2014 Nov 20;515(7527):431-435
pubmed: 25383517
Front Cell Dev Biol. 2020 Nov 26;8:594416
pubmed: 33324647
Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):E5167-E5176
pubmed: 28611221
Oncotarget. 2016 Dec 6;7(49):80131-80139
pubmed: 27741510
FASEB J. 2020 Dec;34(12):16333-16347
pubmed: 33058299
Nat Commun. 2020 Feb 14;11(1):889
pubmed: 32060352
Biochim Biophys Acta. 1995 May 24;1271(1):165-70
pubmed: 7599204
Pediatr Res. 2009 Aug;66(2):121-7
pubmed: 19390491
Exp Gerontol. 2011 Nov;46(11):847-52
pubmed: 21884780
J Inherit Metab Dis. 2015 Jul;38(4):703-19
pubmed: 26025548
Front Cell Dev Biol. 2020 Apr 15;8:239
pubmed: 32373609
Nat Rev Mol Cell Biol. 2020 Apr;21(4):204-224
pubmed: 32071438
Biochem J. 2005 Dec 1;392(Pt 2):353-62
pubmed: 16076285
Cell Metab. 2015 Aug 4;22(2):204-6
pubmed: 26073494
FEBS Lett. 2018 Mar;592(5):743-758
pubmed: 29106705
Am J Hum Biol. 2012 Mar-Apr;24(2):101-6
pubmed: 22290875
Trends Biochem Sci. 2016 Aug;41(8):700-711
pubmed: 27283514
Cell Death Differ. 2013 Jan;20(1):31-42
pubmed: 22743996
Aging Cell. 2013 Dec;12(6):966-77
pubmed: 23795962
EMBO J. 2012 Mar 7;31(5):1095-108
pubmed: 22343943
Aging Cell. 2004 Feb;3(1):35-40
pubmed: 14965354
PLoS One. 2011 Mar 31;6(3):e18433
pubmed: 21483800
J Mol Biol. 2018 Oct 19;430(21):3873-3891
pubmed: 29626541
J Clin Endocrinol Metab. 2016 Dec;101(12):4994-5003
pubmed: 27710240
EMBO Rep. 2020 Apr 3;21(4):e49113
pubmed: 32043300
Biochim Biophys Acta. 2009 Oct;1790(10):1005-14
pubmed: 19524016
Nature. 2012 Dec 13;492(7428):261-5
pubmed: 23172144
Cell. 2021 Jan 7;184(1):33-63
pubmed: 33340459
J Pharmacol Exp Ther. 2019 May;369(2):282-290
pubmed: 30846619
Front Genet. 2017 Sep 01;8:113
pubmed: 28919908
Front Physiol. 2020 Nov 11;11:541040
pubmed: 33262702
Mol Cell. 2016 Jan 21;61(2):199-209
pubmed: 26725009
FASEB J. 2019 Dec;33(12):13176-13188
pubmed: 31480917
Front Endocrinol (Lausanne). 2019 May 07;10:294
pubmed: 31133988
Nature. 2020 Jul;583(7814):122-126
pubmed: 32461692
Hum Mol Genet. 2007 Feb 15;16(4):431-44
pubmed: 17210671
Mol Cell. 2016 Mar 3;61(5):654-666
pubmed: 26942670
Development. 2016 Jan 1;143(1):3-14
pubmed: 26732838
JAMA Netw Open. 2018 Oct 5;1(6):e183605
pubmed: 30646252
Geroscience. 2020 Apr;42(2):749-764
pubmed: 31975050
PLoS Biol. 2010 Dec 07;8(12):e1000556
pubmed: 21151885
Nat Rev Mol Cell Biol. 2019 Jul;20(7):421-435
pubmed: 30733602
Blood. 2014 May 1;123(18):2864-72
pubmed: 24677541
J Gerontol A Biol Sci Med Sci. 2001 Nov;56(11):B475-82
pubmed: 11682568
Science. 2010 Apr 16;328(5976):321-6
pubmed: 20395504
EMBO J. 1999 Apr 1;18(7):1783-92
pubmed: 10202142
Exp Gerontol. 2010 Jun;45(6):410-8
pubmed: 20350594
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6491-6501
pubmed: 32152094
Aging Cell. 2008 Aug;7(4):552-60
pubmed: 18505478
Science. 2002 Dec 20;298(5602):2398-401
pubmed: 12471266
Cell Calcium. 2005 Sep-Oct;38(3-4):311-7
pubmed: 16087232
J Cell Biol. 2018 Jan 2;217(1):51-63
pubmed: 29127110
Nature. 2013 Jan 17;493(7432):338-45
pubmed: 23325216
Cell Metab. 2007 Oct;6(4):280-93
pubmed: 17908557
Front Genet. 2015 Jul 22;6:247
pubmed: 26257774
Ann Clin Transl Neurol. 2019 Sep;6(9):1877-1881
pubmed: 31386302
Cell Metab. 2014 Jul 1;20(1):10-25
pubmed: 24726383
Nature. 2015 Jul 30;523(7562):617-20
pubmed: 26223627
Cell Metab. 2017 Dec 5;26(6):884-896.e5
pubmed: 29107506
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6400-5
pubmed: 23509287
Cell. 2019 Apr 4;177(2):299-314.e16
pubmed: 30929899
Cell Metab. 2018 Nov 6;28(5):776-786.e5
pubmed: 30122556
Cell. 2013 Oct 24;155(3):699-712
pubmed: 24243023
Interdiscip Top Gerontol. 2015;40:107-27
pubmed: 25341517
Mitochondrion. 2020 Sep;54:72-84
pubmed: 32738358
Cell. 2020 Oct 1;183(1):62-75.e17
pubmed: 32946811
Cell. 2020 Jan 23;180(2):296-310.e18
pubmed: 31978346
Cell. 2020 Mar 5;180(5):968-983.e24
pubmed: 32109415
Nat Commun. 2015 May 11;6:7007
pubmed: 25959678
Aging Cell. 2018 Aug;17(4):e12769
pubmed: 29696791
Biol Signals Recept. 2001 May-Aug;10(3-4):176-88
pubmed: 11351127
PLoS One. 2017 Nov 21;12(11):e0188421
pubmed: 29161316
Cell Metab. 2012 Jul 3;16(1):18-31
pubmed: 22768836
Kidney Int. 2019 Feb;95(2):455-466
pubmed: 30471880
Nature. 2019 Jul;571(7766):515-520
pubmed: 31341297
PLoS Genet. 2009 Feb;5(2):e1000361
pubmed: 19197346
EMBO J. 2019 Nov 15;38(22):e101056
pubmed: 31609012
Exp Gerontol. 2021 Mar;145:111182
pubmed: 33290862
Ageing Res Rev. 2012 Apr;11(2):230-41
pubmed: 22186033
Mol Cell. 2020 Feb 6;77(3):645-655.e7
pubmed: 31983508
Exp Gerontol. 2014 Aug;56:142-6
pubmed: 24518875
Lancet. 2017 Dec 16;390(10113):2643-2654
pubmed: 28943267
Front Cell Dev Biol. 2019 Nov 06;7:274
pubmed: 31781563
Trends Endocrinol Metab. 2016 Feb;27(2):105-117
pubmed: 26754340
Nature. 2007 Nov 29;450(7170):736-40
pubmed: 18046414
Antioxid Redox Signal. 2019 Sep 20;31(9):623-642
pubmed: 30784294
Redox Biol. 2020 Oct;37:101674
pubmed: 32811789
Geroscience. 2021 Apr;43(2):517-537
pubmed: 33634362
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2278-83
pubmed: 11226230
Ann N Y Acad Sci. 1998 Nov 20;854:224-38
pubmed: 9928433
Elife. 2016 Mar 23;5:
pubmed: 27008180
Cell Rep. 2020 Nov 24;33(8):108423
pubmed: 33238124
Nat Cell Biol. 2018 Mar;20(3):352-360
pubmed: 29358705
Nat Metab. 2020 Dec;2(12):1472-1481
pubmed: 33324011
Elife. 2020 Dec 15;9:
pubmed: 33319746
Arch Biochem Biophys. 1999 May 1;365(1):131-42
pubmed: 10222047
Mol Cell Biochem. 1997 Sep;174(1-2):305-19
pubmed: 9309704
Cell Rep. 2017 Apr 18;19(3):487-496
pubmed: 28423313
Nat Commun. 2018 Nov 30;9(1):5111
pubmed: 30504768
Nat Commun. 2021 Jan 20;12(1):479
pubmed: 33473112
Genetics. 2012 Dec;192(4):1203-34
pubmed: 23212899
Sci Rep. 2021 Feb 8;11(1):3319
pubmed: 33558594
Geroscience. 2020 Aug;42(4):1175-1182
pubmed: 32572752
J Physiol. 2019 Nov;597(22):5411-5428
pubmed: 31490555
FEBS Lett. 1971 Nov 1;18(2):261-264
pubmed: 11946135
Dev Cell. 2001 Nov;1(5):633-44
pubmed: 11709184
Antioxid Redox Signal. 2010 Apr;12(4):503-35
pubmed: 19650712
Nat Commun. 2014 Mar 24;5:3483
pubmed: 24662282
Am J Physiol Endocrinol Metab. 2005 Sep;289(3):E429-38
pubmed: 15886224
Biophys J. 2019 Aug 20;117(4):631-645
pubmed: 31400914
Genes Dev. 2020 Mar 1;34(5-6):428-445
pubmed: 32001510
Aging Cell. 2006 Dec;5(6):463-71
pubmed: 17054663