Role of mitophagy in the hallmarks of aging

Jie Wen; Tingyu Pan; Hongyan Li; Haixia Fan; Jinhua Liu; Zhiyou Cai; Bin Zhao

doi:10.7555/JBR.36.20220045

Volume 37 Issue 1

Jan. 2023

Turn off MathJax

Article Contents

Article Navigation > The Journal of Biomedical Research > 2023 > 37(1): 1-14

Jie Wen, Tingyu Pan, Hongyan Li, Haixia Fan, Jinhua Liu, Zhiyou Cai, Bin Zhao. Role of mitophagy in the hallmarks of aging[J]. The Journal of Biomedical Research, 2023, 37(1): 1-14. doi: 10.7555/JBR.36.20220045

Citation:

Jie Wen, Tingyu Pan, Hongyan Li, Haixia Fan, Jinhua Liu, Zhiyou Cai, Bin Zhao. Role of mitophagy in the hallmarks of aging[J]. The Journal of Biomedical Research, 2023, 37(1): 1-14. doi: 10.7555/JBR.36.20220045

Citation:

PDF( 7871 KB)

Role of mitophagy in the hallmarks of aging

doi: 10.7555/JBR.36.20220045

Jie Wen^{1, 2, 3, 4},
Tingyu Pan^{3, 4},
Hongyan Li^{3, 4, 5},
Haixia Fan⁶,
Jinhua Liu^{1, 2},
Zhiyou Cai^{3, 4
,
,},
Bin Zhao^{1, 2
,
,}

1.
Department and Institute of Neurology, Guangdong Medical University, Zhanjiang, Guangdong 524001, China
2.
Guangdong Key Laboratory of Aging-related Cardiac and Cerebral Diseases, Zhanjiang, Guangdong 524001, China
3.
Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing 400013, China
4.
Department of Neurology, Chongqing General Hospital, Chongqing 400013, China
5.
Department of Neurology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
6.
Chongqing Medical University, Chongqing 400042, China

More Information

Corresponding author: Zhiyou Cai, Department of Neurology, Chongqing General Hospital, 312 Zhongshan First Road, Yuzhong District, Chongqing 400013, China. Tel/Fax: +86-23-63515796/+86-23-63515796, E-mail: caizhiyou@ucas.ac.cn; Bin Zhao, Department and Institute of Neurology, Guangdong Medical University, Guangdong Key Laboratory of Aging-related Cardiac and Cerebral Diseases, 57 Renmin Road, Zhanjiang, Guangdong 524001, China. Tel/Fax: +86-759-2386949/+86-13902501596, E-mail: binzhaoe@gdmu.edu.cn/binzhaoe@163.com
Received: 2022-03-10
Revised: 2022-06-10
Accepted: 2022-06-27

Published: 2022-08-28

Issue Date: 2023-01-28

Abstract

Abstract

Aging, subjected to scientific scrutiny, is extensively defined as a time-dependent decline in functions that involves the majority of organisms. The time-dependent accretion of cellular lesions is generally a universal trigger of aging, while mitochondrial dysfunction is a sign of aging. Dysfunctional mitochondria are identified and removed by mitophagy, a selective form of macroautophagy. Increased mitochondrial damage resulting from reduced biogenesis and clearance may promote the aging process. The primary purpose of this paper is to illustrate in detail the effects of mitophagy on aging and emphasize the associations between mitophagy and other signs of aging, including dietary restriction, telomere shortening, epigenetic alterations, and protein imbalance. The evidence regarding the effects of these elements on aging is still limited. And although the understanding of relationship between mitophagy and aging has been long-awaited, to analyze details of such a relationship remains the main challenge in aging studies.
- mitophagy,
- aging,
- dietary restriction,
- telomere shortening,
- epigenetic alterations,
- protein imbalance

CLC number: R363, Document code: A
The authors reported no conflict of interests.

FullText(HTML)

References(134)

References

[1]	Borgoni S, Kudryashova KS, Burka K, et al. Targeting immune dysfunction in aging[J]. Ageing Res Rev, 2021, 70: 101410. doi: 10.1016/j.arr.2021.101410
[2]	Szilard L. On the nature of the aging process[J]. Proc Natl Acad Sci U S A, 1959, 45(1): 30–45. doi: 10.1073/pnas.45.1.30
[3]	Lombard DB, Chua KF, Mostoslavsky R, et al. DNA repair, genome stability, and aging[J]. Cell, 2005, 120(4): 497–512. doi: 10.1016/j.cell.2005.01.028
[4]	Forster MJ, Dubey A, Dawson KM, et al. Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain[J]. Proc Natl Acad Sci U S A, 1996, 93(10): 4765–4769. doi: 10.1073/pnas.93.10.4765
[5]	ScialòF, Sriram A, Fernández-Ayala D, et al. Mitochondrial ROS produced via reverse electron transport extend animal lifespan[J]. Cell Metab, 2016, 23(4): 725–734. doi: 10.1016/j.cmet.2016.03.009
[6]	Detmer SA, Chan DC. Functions and dysfunctions of mitochondrial dynamics[J]. Nat Rev Mol Cell Biol, 2007, 8(11): 870–879. doi: 10.1038/nrm2275
[7]	Narendra D, Tanaka A, Suen DF, et al. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy[J]. J Cell Biol, 2008, 183(5): 795–803. doi: 10.1083/jcb.200809125
[8]	Zhou H, Ren J, Toan S, et al. Role of mitochondrial quality surveillance in myocardial infarction: from bench to bedside[J]. Ageing Res Rev, 2021, 66: 101250. doi: 10.1016/j.arr.2020.101250
[9]	Sukhorukov V, Voronkov D, Baranich T, et al. Impaired mitophagy in neurons and glial cells during aging and age-related disorders[J]. Int J Mol Sci, 2021, 22(19): 10251. doi: 10.3390/ijms221910251
[10]	Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release[J]. Physiol Rev, 2014, 94(3): 909–950. doi: 10.1152/physrev.00026.2013
[11]	McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse[J]. Curr Biol, 2006, 16(14): R551–R560. doi: 10.1016/j.cub.2006.06.054
[12]	Harman D. Aging: a theory based on free radical and radiation chemistry[J]. J Gerontol, 1956, 11(3): 298–300. doi: 10.1093/geronj/11.3.298
[13]	López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging[J]. Cell, 2013, 153(6): 1194–1217. doi: 10.1016/j.cell.2013.05.039
[14]	Krysko DV, Agostinis P, Krysko O, et al. Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation[J]. Trends Immunol, 2011, 32(4): 157–164. doi: 10.1016/j.it.2011.01.005
[15]	Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury[J]. Nature, 2010, 464(7285): 104–107. doi: 10.1038/nature08780
[16]	Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling[J]. Nat Rev Immunol, 2016, 16(7): 407–420. doi: 10.1038/nri.2016.58
[17]	Yu J, Nagasu H, Murakami T, et al. Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy[J]. Proc Natl Acad Sci U S A, 2014, 111(43): 15514–15519. doi: 10.1073/pnas.1414859111
[18]	Baloyannis SJ. Mitochondrial alterations in Alzheimer's disease[J]. J Alzheimers Dis, 2006, 9(2): 119–126. doi: 10.3233/JAD-2006-9204
[19]	Trushina E, Nemutlu E, Zhang S, et al. Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer's disease[J]. PLoS One, 2012, 7(2): e32737. doi: 10.1371/journal.pone.0032737
[20]	Morton H, Kshirsagar S, Orlov E, et al. Defective mitophagy and synaptic degeneration in Alzheimer's disease: focus on aging, mitochondria and synapse[J]. Free Radic Biol Med, 2021, 172: 652–667. doi: 10.1016/j.freeradbiomed.2021.07.013
[21]	Kandimalla R, Manczak M, Pradeepkiran JA, et al. A partial reduction of Drp1 improves cognitive behavior and enhances mitophagy, autophagy and dendritic spines in a transgenic tau mouse model of Alzheimer disease[J]. Hum Mol Genet, 2022, 31(11): 1788–1805. doi: 10.1093/hmg/ddab360
[22]	Reddy PH, Tripathi R, Troung Q, et al. Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: implications to mitochondria-targeted antioxidant therapeutics[J]. Biochim Biophys Acta (BBA)-Mol Basis Dis, 2012, 1822(5): 639–649. doi: 10.1016/j.bbadis.2011.10.011
[23]	Grünewald A, Voges L, Rakovic A, et al. Mutant Parkin impairs mitochondrial function and morphology in human fibroblasts[J]. PLoS One, 2010, 5(9): e12962. doi: 10.1371/journal.pone.0012962
[24]	Geisler S, Holmström KM, Treis A, et al. The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations[J]. Autophagy, 2010, 6(7): 871–878. doi: 10.4161/auto.6.7.13286
[25]	Narendra D, Walker JE, Youle R. Mitochondrial quality control mediated by PINK1 and Parkin: links to parkinsonism[J]. Cold Spring Harb Perspect Biol, 2012, 4(11): a011338. doi: 10.1101/cshperspect.a011338
[26]	Swerdlow NS, Wilkins HM. Mitophagy and the brain[J]. Int J Mol Sci, 2020, 21(24): 9661. doi: 10.3390/ijms21249661
[27]	Meissner C, Lorenz H, Weihofen A, et al. The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking[J]. J Neurochem, 2011, 117(5): 856–867. doi: 10.1111/j.1471-4159.2011.07253.x
[28]	Jin SM, Lazarou M, Wang C, et al. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL[J]. J Cell Biol, 2010, 191(5): 933–942. doi: 10.1083/jcb.201008084
[29]	Rakovic A, Shurkewitsch K, Seibler P, et al. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons[J]. J Biol Chem, 2013, 288(4): 2223–2237. doi: 10.1074/jbc.M112.391680
[30]	Jin SM, Youle RJ. PINK1- and Parkin-mediated mitophagy at a glance[J]. J Cell Sci, 2012, 125(Pt 4): 795–799. doi: 10.1242/jcs.093849
[31]	Narendra DP, Jin SM, Tanaka A, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin[J]. PLoS Biol, 2010, 8(1): e1000298. doi: 10.1371/journal.pbio.1000298
[32]	Matsuda N, Sato S, Shiba K, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy[J]. J Cell Biol, 2010, 189(2): 211–221. doi: 10.1083/jcb.200910140
[33]	Hanna RA, Quinsay MN, Orogo AM, et al. Microtubule-associated protein 1 light chain 3 (LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy[J]. J Biol Chem, 2012, 287(23): 19094–19104. doi: 10.1074/jbc.M111.322933
[34]	Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy[J]. Cell Death Differ, 2009, 16(7): 939–946. doi: 10.1038/cdd.2009.16
[35]	Liu L, Feng D, Chen G, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells[J]. Nat Cell Biol, 2012, 14(2): 177–185. doi: 10.1038/ncb2422
[36]	Feng D, Liu L, Zhu Y, et al. Molecular signaling toward mitophagy and its physiological significance[J]. Exp Cell Res, 2013, 319(12): 1697–1705. doi: 10.1016/j.yexcr.2013.03.034
[37]	Wei H, Liu L, Chen Q. Selective removal of mitochondria via mitophagy: distinct pathways for different mitochondrial stresses[J]. Biochim Biophys Acta (BBA)- Mol Cell Res, 2015, 1853(10): 2784–2790. doi: 10.1016/j.bbamcr.2015.03.013
[38]	Sowter HM, Ratcliffe PJ, Watson P, et al. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors[J]. Cancer Res, 2001, 61(18): 6669–6673. https://pubmed.ncbi.nlm.nih.gov/11559532/
[39]	Liu KE, Frazier WA. Phosphorylation of the BNIP3 C-terminus inhibits mitochondrial damage and cell death without blocking autophagy[J]. PLoS One, 2015, 10(6): e0129667. doi: 10.1371/journal.pone.0129667
[40]	Rogov VV, Suzuki H, Marinković M, et al. Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins[J]. Sci Rep, 2017, 7(1): 1131. doi: 10.1038/s41598-017-01258-6
[41]	Ma K, Zhang Z, Chang R, et al. Dynamic PGAM5 multimers dephosphorylate BCL-xL or FUNDC1 to regulate mitochondrial and cellular fate[J]. Cell Death Differ, 2020, 27(3): 1036–1051. doi: 10.1038/s41418-019-0396-4
[42]	Chen G, Han Z, Feng D, et al. A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy[J]. Mol Cell, 2014, 54(3): 362–377. doi: 10.1016/j.molcel.2014.02.034
[43]	Chen Z, Liu L, Cheng Q, et al. Mitochondrial E3 ligase MARCH5 regulates FUNDC1 to fine-tune hypoxic mitophagy[J]. EMBO Rep, 2017, 18(3): 495–509. doi: 10.15252/embr.201643309
[44]	Zhou H, Wang J, Zhu P, et al. NR4A1 aggravates the cardiac microvascular ischemia reperfusion injury through suppressing FUNDC1-mediated mitophagy and promoting Mff-required mitochondrial fission by CK2α[J]. Basic Res Cardiol, 2018, 113(4): 23. doi: 10.1007/s00395-018-0682-1
[45]	Zhou H, Li D, Zhu P, et al. Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARγ/FUNDC1/mitophagy pathways[J]. J Pineal Res, 2017, 63(4): e12438. doi: 10.1111/jpi.12438
[46]	Zhang T, Xue L, Li L, et al. BNIP3 protein suppresses PINK1 kinase proteolytic cleavage to promote mitophagy[J]. J Biol Chem, 2016, 291(41): 21616–21629. doi: 10.1074/jbc.M116.733410
[47]	Davis CHO, Marsh-Armstrong N. Discovery and implications of transcellular mitophagy[J]. Autophagy, 2014, 10(12): 2383–2384. doi: 10.4161/15548627.2014.981920
[48]	Davis CHO, Kim KY, Bushong EA, et al. Transcellular degradation of axonal mitochondria[J]. Proc Natl Acad Sci U S A, 2014, 111(26): 9633–9638. doi: 10.1073/pnas.1404651111
[49]	Bakula D, Scheibye-Knudsen M. MitophAging: mitophagy in aging and disease[J]. Front Cell Dev Biol, 2020, 8: 239. doi: 10.3389/fcell.2020.00239
[50]	Jang JY, Blum A, Liu J, et al. The role of mitochondria in aging[J]. J Clin Invest, 2018, 128(9): 3662–3670. doi: 10.1172/JCI120842
[51]	Pradeepkiran JA, Reddy PH. Defective mitophagy in Alzheimer's disease[J]. Ageing Res Rev, 2020, 64: 101191. doi: 10.1016/j.arr.2020.101191
[52]	Santoro A, Salvioli S, Raule N, et al. Mitochondrial DNA involvement in human longevity[J]. Biochim Biophys Acta, 2006, 1757(9–10): 1388–1399. doi: 10.1016/j.bbabio.2006.05.040
[53]	Salvioli S, Olivieri F, Marchegiani F, et al. Genes, ageing and longevity in humans: problems, advantages and perspectives[J]. Free Radic Res, 2006, 40(12): 1303–1323. doi: 10.1080/10715760600917136
[54]	Rose G, Santoro A, Salvioli S. Mitochondria and mitochondria-induced signalling molecules as longevity determinants[J]. Mech Ageing Dev, 2017, 165: 115–128. doi: 10.1016/j.mad.2016.12.002
[55]	Fritsch LE, Moore ME, Sarraf SA, et al. Ubiquitin and receptor-dependent mitophagy pathways and their implication in neurodegeneration[J]. J Mol Biol, 2020, 432(8): 2510–2524. doi: 10.1016/j.jmb.2019.10.015
[56]	Wang Y, Liu N, Lu B. Mechanisms and roles of mitophagy in neurodegenerative diseases[J]. CNS Neurosci Ther, 2019, 25(7): 859–875. doi: 10.1111/cns.13140
[57]	Zhang X, Wang Y, Wang Y, et al. p53 mediates mitochondria dysfunction-triggered autophagy activation and cell death in rat striatum[J]. Autophagy, 2009, 5(3): 339–350. doi: 10.4161/auto.5.3.8174
[58]	Harper JW, Ordureau A, Heo JM. Building and decoding ubiquitin chains for mitophagy[J]. Nat Rev Mol Cell Biol, 2018, 19(2): 93–108. doi: 10.1038/nrm.2017.129
[59]	Wei M, Brandhorst S, Shelehchi M, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease[J]. Sci Transl Med, 2017, 9(377): eaai8700. doi: 10.1126/scitranslmed.aai8700
[60]	Lee C, Longo VD. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients[J]. Oncogene, 2011, 30(30): 3305–3316. doi: 10.1038/onc.2011.91
[61]	Kapahi P, Kaeberlein M, Hansen M. Dietary restriction and lifespan: lessons from invertebrate models[J]. Ageing Res Rev, 2017, 39: 3–14. doi: 10.1016/j.arr.2016.12.005
[62]	Brandhorst S, Harputlugil E, Mitchell JR, et al. Protective effects of short-term dietary restriction in surgical stress and chemotherapy[J]. Ageing Res Rev, 2017, 39: 68–77. doi: 10.1016/j.arr.2017.02.001
[63]	Madia F, Wei M, Yuan V, et al. Oncogene homologue Sch9 promotes age-dependent mutations by a superoxide and Rev1/Polζ-dependent mechanism[J]. J Cell Biol, 2009, 186(4): 509–523. doi: 10.1083/jcb.200906011
[64]	Fontana L, Partridge L, Longo VD. Extending healthy life span-from yeast to humans[J]. Science, 2010, 328(5976): 321–326. doi: 10.1126/science.1172539
[65]	Longo VD, Finch CE. Evolutionary medicine: from dwarf model systems to healthy centenarians?[J]. Science, 2003, 299(5611): 1342–1346. doi: 10.1126/science.1077991
[66]	Kenyon C. A conserved regulatory system for aging[J]. Cell, 2001, 105(2): 165–168. doi: 10.1016/S0092-8674(01)00306-3
[67]	Guarente L, Kenyon C. Genetic pathways that regulate ageing in model organisms[J]. Nature, 2000, 408(6809): 255–262. doi: 10.1038/35041700
[68]	Boya P, González-Polo RA, Casares N, et al. Inhibition of macroautophagy triggers apoptosis[J]. Mol Cell Biol, 2005, 25(3): 1025–1040. doi: 10.1128/MCB.25.3.1025-1040.2005
[69]	Mehrabani S, Bagherniya M, Askari G, et al. The effect of fasting or calorie restriction on mitophagy induction: a literature review[J]. J Cachexia, Sarcopenia Muscle, 2020, 11(6): 1447–1458. doi: 10.1002/jcsm.12611
[70]	Martin-Montalvo A, de Cabo R. Mitochondrial metabolic reprogramming induced by calorie restriction[J]. Antioxid Redox Signal, 2013, 19(3): 310–320. doi: 10.1089/ars.2012.4866
[71]	Finley LWS, Lee J, Souza A, et al. Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction[J]. Proc Natl Acad Sci U S A, 2012, 109(8): 2931–2936. doi: 10.1073/pnas.1115813109
[72]	Niemann B, Chen Y, Issa H, et al. Caloric restriction delays cardiac ageing in rats: role of mitochondria[J]. Cardiovasc Res, 2010, 88(2): 267–276. doi: 10.1093/cvr/cvq273
[73]	Picca A, Pesce V, Lezza AMS. Does eating less make you live longer and better? An update on calorie restriction[J]. Clin Interv Aging, 2017, 12: 1887–1902. doi: 10.2147/CIA.S126458
[74]	Barzilai N, Huffman DM, Muzumdar RH, et al. The critical role of metabolic pathways in aging[J]. Diabetes, 2012, 61(6): 1315–1322. doi: 10.2337/db11-1300
[75]	Houtkooper RH, Williams RW, Auwerx J. Metabolic networks of longevity[J]. Cell, 2010, 142(1): 9–14. doi: 10.1016/j.cell.2010.06.029
[76]	Laplante M, Sabatini DM. mTOR signaling in growth control and disease[J]. Cell, 2012, 149(2): 274–293. doi: 10.1016/j.cell.2012.03.017
[77]	Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease[J]. Nature, 2013, 493(7432): 338–345. doi: 10.1038/nature11861
[78]	Kaeberlein M, Powers III RW, Steffen KK, et al. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients[J]. Science, 2005, 310(5751): 1193–1196. doi: 10.1126/science.1115535
[79]	Hansen M, Taubert S, Crawford D, et al. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans[J]. Aging cell, 2007, 6(1): 95–110. doi: 10.1111/j.1474-9726.2006.00267.x
[80]	Alers S, Löffler AS, Wesselborg S, et al. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks[J]. Mol Cell Biol, 2012, 32(1): 2–11. doi: 10.1128/MCB.06159-11
[81]	Penev A, Markiewicz-Potoczny M, Sfeir A, et al. Stem cells at odds with telomere maintenance and protection[J]. Trends Cell Biol, 2022, 32(6): 527–536. doi: 10.1016/j.tcb.2021.12.007
[82]	Shammas MA. Telomeres, lifestyle, cancer, and aging[J]. Curr Opin Clin Nutr Metab Care, 2011, 14(1): 28–34. doi: 10.1097/MCO.0b013e32834121b1
[83]	Nguyen THD, Tam J, Wu RA, et al. Cryo-EM structure of substrate-bound human telomerase holoenzyme[J]. Nature, 2018, 557(7704): 190–195. doi: 10.1038/s41586-018-0062-x
[84]	Blackburn EH, Greider CW, Szostak JW. Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging[J]. Nat Med, 2006, 12(10): 1133–1138. doi: 10.1038/nm1006-1133
[85]	Tran M, Reddy PH. Defective autophagy and mitophagy in aging and Alzheimer's disease[J]. Front Neurosci, 2021, 14: 612757. doi: 10.3389/fnins.2020.612757
[86]	Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains[J]. Exp Cell Res, 1961, 25(3): 585–621. doi: 10.1016/0014-4827(61)90192-6
[87]	Correia-Melo C, Passos JF. Mitochondria: are they causal players in cellular senescence?[J]. Biochim Biophys Acta (BBA)-Bioenerg, 2015, 1847(11): 1373–1379. doi: 10.1016/j.bbabio.2015.05.017
[88]	Summer R, Shaghaghi H, Schriner D, et al. Activation of the mTORC1/PGC-1 axis promotes mitochondrial biogenesis and induces cellular senescence in the lung epithelium[J]. Am J Physiol Lung Cell Mol Physiol, 2019, 316(6): L1049–L1060. doi: 10.1152/ajplung.00244.2018
[89]	Hoffmann RF, Zarrintan S, Brandenburg SM, et al. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells[J]. Respir Res, 2013, 14(1): 97. doi: 10.1186/1465-9921-14-97
[90]	Rossi DJ, Bryder D, Seita J, et al. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age[J]. Nature, 2007, 447(7145): 725–729. doi: 10.1038/nature05862
[91]	Green DR, Galluzzi L, Kroemer G. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging[J]. Science, 2011, 333(6046): 1109–1112. doi: 10.1126/science.1201940
[92]	Calió ML, Henriques E, Siena A, et al. Mitochondrial dysfunction, neurogenesis, and epigenetics: putative implications for amyotrophic lateral sclerosis neurodegeneration and treatment[J]. Front Neurosci, 2020, 14: 679. doi: 10.3389/fnins.2020.00679
[93]	Fraga MF, Esteller M. Epigenetics and aging: the targets and the marks[J]. Trends Genet, 2007, 23(8): 413–418. doi: 10.1016/j.tig.2007.05.008
[94]	Han S, Brunet A. Histone methylation makes its mark on longevity[J]. Trends Cell Biol, 2012, 22(1): 42–49. doi: 10.1016/j.tcb.2011.11.001
[95]	Okano M, Bell DW, Haber DA, et al. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development[J]. Cell, 1999, 99(3): 247–257. doi: 10.1016/S0092-8674(00)81656-6
[96]	Shock LS, Thakkar PV, Peterson EJ, et al. DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria[J]. Proc Natl Acad Sci U S A, 2011, 108(9): 3630–3635. doi: 10.1073/pnas.1012311108
[97]	Felsenfeld G, Groudine M. Controlling the double helix[J]. Nature, 2003, 421(6921): 448–453. doi: 10.1038/nature01411
[98]	Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain[J]. Science, 2009, 324(5929): 929–930. doi: 10.1126/science.1169786
[99]	Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1[J]. Science, 2009, 324(5929): 930–935. doi: 10.1126/science.1170116
[100]	Park YJ, Lee S, Lim S, et al. DNMT1 maintains metabolic fitness of adipocytes through acting as an epigenetic safeguard of mitochondrial dynamics[J]. Proc Natl Acad Sci U S A, 2021, 118(11): e2021073118. doi: 10.1073/pnas.2021073118
[101]	Greer EL, Maures TJ, Hauswirth AG, et al. Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans[J]. Nature, 2010, 466(7304): 383–387. doi: 10.1038/nature09195
[102]	Siebold AP, Banerjee R, Tie F, et al. Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance[J]. Proc Natl Acad Sci U S A, 2010, 107(1): 169–174. doi: 10.1073/pnas.0907739107
[103]	Pietrocola F, Galluzzi L, Pedro JMBS, et al. Acetyl coenzyme A: a central metabolite and second messenger[J]. Cell Metabolism, 2015, 21(6): 805–821. doi: 10.1016/j.cmet.2015.05.014
[104]	Gao AW, Cantó C, Houtkooper RH. Mitochondrial response to nutrient availability and its role in metabolic disease[J]. EMBO Mol Med, 2014, 6(5): 580–589. doi: 10.1002/emmm.201303782
[105]	Ambekar T, Pawar J, Rathod R, et al. Mitochondrial quality control: epigenetic signatures and therapeutic strategies[J]. Neurochem Int, 2021, 148: 105095. doi: 10.1016/j.neuint.2021.105095
[106]	Dong Y, Yoshitomi T, Hu J, et al. Long noncoding RNAs coordinate functions between mitochondria and the nucleus[J]. Epigenetics Chromatin, 2017, 10(1): 41. doi: 10.1186/s13072-017-0149-x
[107]	Li Y, Xu S, Xu D, et al. Pediatric pan-central nervous system tumor methylome analyses reveal immune-related LncRNAs[J]. Front Immunol, 2022, 13: 853904. doi: 10.3389/fimmu.2022.853904
[108]	Zhao Y, Sun L, Wang RR, et al. The effects of mitochondria-associated long noncoding RNAs in cancer mitochondria: new players in an old arena[J]. Crit Rev Oncol Hematol, 2018, 131: 76–82. doi: 10.1016/j.critrevonc.2018.08.005
[109]	Anand A, Pandi G. Noncoding RNA: an insight into chloroplast and mitochondrial gene expressions[J]. Life, 2021, 11(1): 49. doi: 10.3390/life11010049
[110]	Bárcena C, Mayoral P, Quirós PM. Mitohormesis, an antiaging paradigm[J]. Int Rev Cell Mol Biol, 2018, 340: 35–77. doi: 10.1016/bs.ircmb.2018.05.002
[111]	English J, Son JM, Cardamone MD, et al. Decoding the rosetta stone of mitonuclear communication[J]. Pharmacol Res, 2020, 161: 105161. doi: 10.1016/j.phrs.2020.105161
[112]	Rackham O, Shearwood AMJ, Mercer TR, et al. Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins[J]. RNA, 2011, 17(12): 2085–2093. doi: 10.1261/rna.029405.111
[113]	Xiang X, Fu Y, Zhao K, et al. Cellular senescence in hepatocellular carcinoma induced by a long non-coding RNA-encoded peptide PINT87aa by blocking FOXM1-mediated PHB2[J]. Theranostics, 2021, 11(10): 4929–4944. doi: 10.7150/thno.55672
[114]	Tai Y, Chen J, Tao Z, et al. Non-coding RNAs: new players in mitophagy and neurodegeneration[J]. Neurochem Int, 2022, 152: 105253. doi: 10.1016/j.neuint.2021.105253
[115]	Koga H, Kaushik S, Cuervo AM. Protein homeostasis and aging: the importance of exquisite quality control[J]. Ageing Res Rev, 2011, 10(2): 205–215. doi: 10.1016/j.arr.2010.02.001
[116]	Münch C. The different axes of the mammalian mitochondrial unfolded protein response[J]. BMC Biol, 2018, 16(1): 81. doi: 10.1186/s12915-018-0548-x
[117]	Drake JC, Yan Z. Mitophagy in maintaining skeletal muscle mitochondrial proteostasis and metabolic health with ageing[J]. J Physiol, 2017, 595(20): 6391–6399. doi: 10.1113/JP274337
[118]	Hartl FU, Bracher A, Hayer-Hartl M. Molecular chaperones in protein folding and proteostasis[J]. Nature, 2011, 475(7356): 324–332. doi: 10.1038/nature10317
[119]	Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion[J]. Nature, 2008, 451(7182): 1069–1075. doi: 10.1038/nature06639
[120]	Powers ET, Morimoto RI, Dillin A, et al. Biological and chemical approaches to diseases of proteostasis deficiency[J]. Annu Rev Biochem, 2009, 78: 959–991. doi: 10.1146/annurev.biochem.052308.114844
[121]	Austriaco NR Jr. Review: to bud until death: the genetics of ageing in the yeast, Saccharomyces[J]. Yeast, 1996, 12(7): 623–630. doi: 10.1002/(SICI)1097-0061(19960615)12:7<623::AID-YEA968>3.0.CO;2-G
[122]	Okamoto K, Kondo-Okamoto N, Ohsumi Y. Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy[J]. Dev Cell, 2009, 17(1): 87–97. doi: 10.1016/j.devcel.2009.06.013
[123]	Kanki T, Wang K, Cao Y, et al. Atg32 is a mitochondrial protein that confers selectivity during mitophagy[J]. Dev Cell, 2009, 17(1): 98–109. doi: 10.1016/j.devcel.2009.06.014
[124]	Wang K, Klionsky DJ. Mitochondria removal by autophagy[J]. Autophagy, 2011, 7(3): 297–300. doi: 10.4161/auto.7.3.14502
[125]	Schulz AM, Haynes CM. UPR^mt-mediated cytoprotection and organismal aging[J]. Biochim Biophys Acta (BBA)-Bioenerg, 2015, 1847(11): 1448–1456. doi: 10.1016/j.bbabio.2015.03.008
[126]	Tomaru U, Takahashi S, Ishizu A, et al. Decreased proteasomal activity causes age-related phenotypes and promotes the development of metabolic abnormalities[J]. Am J Pathol, 2012, 180(3): 963–972. doi: 10.1016/j.ajpath.2011.11.012
[127]	Dorn II GW, Vega RB, Kelly DP. Mitochondrial biogenesis and dynamics in the developing and diseased heart[J]. Genes Dev, 2015, 29(19): 1981–1991. doi: 10.1101/gad.269894.115
[128]	Weng H, Ma Y, Chen L, et al. A new vision of mitochondrial unfolded protein response to the sirtuin family[J]. Curr Neuropharmacol, 2020, 18(7): 613–623. doi: 10.2174/1570159X18666200123165002
[129]	Potes Y, de Luxán-Delgado B, Rodriguez-González S, et al. Overweight in elderly people induces impaired autophagy in skeletal muscle[J]. Free Radic Biol Med, 2017, 110: 31–41. doi: 10.1016/j.freeradbiomed.2017.05.018
[130]	Sakuma K, Kinoshita M, Ito Y, et al. p62/SQSTM1 but not LC3 is accumulated in sarcopenic muscle of mice[J]. J Cachexia, Sarcopenia Muscle, 2016, 7(2): 204–212. doi: 10.1002/jcsm.12045
[131]	Billia F, Hauck L, Konecny F, et al. PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function[J]. Proc Natl Acad Sci U S A, 2011, 108(23): 9572–9577. doi: 10.1073/pnas.1106291108
[132]	Kubli DA, Zhang X, Lee Y, et al. Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction[J]. J Biol Chem, 2013, 288(2): 915–926. doi: 10.1074/jbc.M112.411363
[133]	Oka T, Hikoso S, Yamaguchi O, et al. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure[J]. Nature, 2012, 485(7397): 251–255. doi: 10.1038/nature10992
[134]	de Magalhães JP, Curado J, Church GM. Meta-analysis of age-related gene expression profiles identifies common signatures of aging[J]. Bioinformatics, 2009, 25(7): 875–881. doi: 10.1093/bioinformatics/btp073