Abstract
We investigated the effects of lifelong aerobic exercise and 8 months of detraining after 10 months of aerobic training on circulation, skeletal muscle oxidative stress, and inflammation in aging rats. Sprague–Dawley rats were randomly assigned to the control (CON), detraining (DET), and lifelong aerobic training (LAT) groups. The DET and LAT groups began aerobic treadmill exercise at the age of 8 months and stopped training at the 18th and 26th month, respectively; all rats were sacrificed when aged 26 months. Compared with CON, LAT remarkably decreased serum and aged skeletal muscle 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. Superoxide dismutase 2(SOD2) levels were higher in the LAT group than in the CON group in skeletal muscle. However, DET remarkably decreased SOD2 protein expression and content in the skeletal muscle and increased malondialdehyde (MDA) level compared with LAT. Compared with LAT, DET remarkably downregulated adiponectin and upregulated tumor necrosis factor alpha (TNF-α) expression, while phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and 70-kDa ribosomal protein S6 kinase (P70S6K) protein expression decreased, and that of FoxO1 and muscle atrophy F-box (MAFbX) proteins increased in the quadriceps femoris. Adiponectin and TNF-α expression in the soleus muscle did not change between groups, whereas that of AKT, mammalian target of rapamycin (mTOR), and P70S6K was lower in the soleus in the DET group than in that in the LAT group. Compared with that in the LAT group, sestrin1 (SES1) and nuclear factor erythroid 2–related factor 2 (Nrf2) protein expression in the DET group was lower, whereas Keap1 mRNA expression was remarkably upregulated in the quadriceps femoris. Interestingly, the protein and mRNA levels of SES1, Nrf2, and Keap1 in soleus muscle did not differ between groups. LAT remarkably upregulated ferritin heavy polypeptide 1(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7member 11 (SLC7A11) protein expression in the quadriceps femoris and soleus muscles, compared with CON. However, compared with LAT, DET downregulated FTH, GPX4, and SLC7A11 protein expression in the quadriceps femoris and soleus muscles. Long-term detraining during the aging phase reverses the improvement effect of lifelong exercise on oxidative stress, inflammation, ferroptosis, and muscle atrophy in aging skeletal muscle. The quadriceps femoris is more evident than the soleus, which may be related to the different changes in the Keap1/Nrf2 pathway in different skeletal muscles.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
References
Abou-Samra M, Selvais CM, Dubuisson N, Brichard SM (2020) Adiponectin and its mimics on skeletal muscle: insulin sensitizers, fat burners, exercise mimickers, muscling pills … or everything together? Int J Mol Sci 21:2620. https://doi.org/10.3390/ijms21072620
Alves FM, Ayton S, Bush AI, Lynch GS, Koopman R (2022) Age-related changes in skeletal muscle iron homeostasis. J Gerontol A Biol Sci Med Sci Glac. https://doi.org/10.1093/gerona/glac139
Anandhan A, Dodson M, Schmidlin CJ, Liu P, Zhang DD (2020) Breakdown of an ironclad defense system: the critical role of NRF2 in mediating ferroptosis. Cell Chem Biol 27:436–447. https://doi.org/10.1016/j.chembiol.2020.03.011
Baek KW, Kim SJ, Kim BG, Jung YK, Hah YS, Moon HY, Yoo JI, Park JS, Kim JS (2022) Effects of lifelong spontaneous exercise on skeletal muscle and angiogenesis in super-aged mice. PLoS ONE 17:e0263457. https://doi.org/10.1371/journal.pone.0263457
Barranco-Ruiz Y, Martínez-Amat A, Casals C, Aragón-Vela J, Rosillo S, Gomes SN, Rivas-García A, Guisado R, Huertas JR (2017) A lifelong competitive training practice attenuates age-related lipid peroxidation. J Physiol Biochem 73:37–48. https://doi.org/10.1007/s13105-016-0522-4
Bar-Shai M, Carmeli E, Ljubuncic P, Reznick AZ (2008) Exercise and immobilization in aging animals: the involvement of oxidative stress and NF-kappaB activation. Free Radic Biol Med 44:202–214. https://doi.org/10.1016/j.freeradbiomed.2007.03.019
Belaya I, Suwa M, Chen T, Giniatullin R, Kanninen KM, Atalay M, Kumagai S (2018) Long-term exercise protects against cellular stresses in aged mice. Oxid Med Cell Longev 2018:2894247. https://doi.org/10.1155/2018/2894247
Bellezza I, Giambanco I, Minelli A, Donato R (2018) Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta Mol Cell Res 1865:721–733. https://doi.org/10.1016/j.bbamcr.2018.02.010
Bickel CS, Cross JM, Bamman MM (2011) Exercise dosing to retain resistance training adaptations in young and older adults. Med Sci Sports Exerc 43:1177–1187. https://doi.org/10.1249/MSS.0b013e318207c15d
Bocalini DS, Carvalho EV, de Sousa AF, Levy RF, Tucci PJ (2010) Exercise training-induced enhancement in myocardial mechanics is lost after 2 weeks of detraining in rats. Eur J Appl Physiol 109:909–914. https://doi.org/10.1007/s00421-010-1406-x
Bradic J, Dragojlovic Ruzicic R, Jeremic J, Petkovic A, Stojic I, Nikolic T, Zivkovic V, Srejovic I, Radovanovic D, Jakovljevic VL (2018) Comparison of training and detraining on redox state of rats: gender specific differences. Gen Physiol Biophys 37:285–297. https://doi.org/10.4149/gpb_2017053
Carrick-Ranson G, Hastings JL, Bhella PS, Fujimoto N, Shibata S, Palmer MD, Boyd K, Livingston S, Dijk E, Levine BD (2014) The effect of lifelong exercise dose on cardiovascular function during exercise. J Appl Physiol (1985) 116:736–745. https://doi.org/10.1152/japplphysiol.00342.2013
Chen GH, Song CC, Pantopoulos K, Wei XL, Zheng H, Luo Z (2022a) Mitochondrial oxidative stress mediated Fe-induced ferroptosis via the NRF2-ARE pathway. Free Radic Biol Med 180:95–107. https://doi.org/10.1016/j.freeradbiomed.2022.01.012
Chen M, Wang Y, Deng S, Lian Z, Yu K (2022b) Skeletal muscle oxidative stress and inflammation in aging: Focus on antioxidant and anti-inflammatory therapy. Front Cell Dev Biol 10:964130. https://doi.org/10.3389/fcell.2022.964130
Criswell D, Powers S, Dodd S, Lawler J, Edwards W, Renshler K, Grinton S (1993) High intensity training-induced changes in skeletal muscle antioxidant enzyme activity. Med Sci Sports Exerc 25:1135–1140
Dinari Ghozhdi H, Heidarianpour A, Keshvari M, Tavassoli H (2021) Exercise training and de-training effects on serum leptin and TNF-α in high fat induced diabetic rats. Diabetol Metab Syndr 13:57. https://doi.org/10.1186/s13098-021-00676-x
Done AJ, Traustadóttir T (2016) Nrf2 mediates redox adaptations to exercise. Redox Biol 10:191–199. https://doi.org/10.1016/j.redox.2016.10.003
El Assar M, Álvarez-Bustos A, Sosa P, Angulo J, Rodríguez-Mañas L (2022) Effect of physical activity/exercise on oxidative stress and inflammation in muscle and vascular aging. Int J Mol Sci 23(15):8713. https://doi.org/10.3390/ijms23158713
Feng H, Liu Y, Gan Y, Li M, Liu R, Liang Z, Liu L, Li L, Chen H, Li G, Tian Z, Liu X, Ma S (2022) AdipoR1 regulates ionizing radiation-induced ferroptosis in HCC cells through Nrf2/xCT pathway. Oxid Med Cell Longev 2022:8091464. https://doi.org/10.1155/2022/8091464
Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando TA, Effros RB, Lucia A, Kleinstreuer N, Slavich GM (2019) Chronic inflammation in the etiology of disease across the life span. Nat Med 25:1822–1832. https://doi.org/10.1038/s41591-019-0675-0
Gordon CJ, Jarema K, Johnstone AF, Phillips PM (2016) Effect of genetic strain and gender on age-related changes in body composition of the laboratory rat. J Toxicol Environ Health A 79:376–392. https://doi.org/10.1080/15287394.2016.1169237
Gschwind YJ, Kressig RW, Lacroix A, Muehlbauer T, Pfenninger B, Granacher U (2013) A best practice fall prevention exercise program to improve balance, strength / power, and psychosocial health in older adults: study protocol for a randomized controlled trial. BMC Geriatr 13:105. https://doi.org/10.1186/1471-2318-13-105
Hoff E, Brechtel L, Strube P, Konstanczak P, Stoltenburg-Didinger G, Perka C, Putzier M (2013) Noninvasive monitoring of training induced muscle adaptation with 31P-MRS: fibre type shifts correlate with metabolic changes. Biomed Res Int 2013:417901. https://doi.org/10.1155/2013/417901
Hyatt JK, Brown EA, Deacon HM, McCall GE (2019) Muscle-specific sensitivity to voluntary physical activity and detraining. Front Physiol 10:1328. https://doi.org/10.3389/fphys.2019.01328
Ivey FM, Tracy BL, Lemmer JT, NessAiver M, Metter EJ, Fozard JL, Hurley BF (2000) Effects of strength training and detraining on muscle quality: age and gender comparisons. J Gerontol A Biol Sci Med Sci 55:B152-157. https://doi.org/10.1093/gerona/55.3.b152
Jiménez-Maldonado A, Virgen-Ortiz A, Lemus M, Castro-Rodríguez E, Cerna-Cortés J, Muñiz J, Montero S, Roces E (2019) Effects of moderate- and high-intensity chronic exercise on the adiponectin levels in slow-twitch and fast-twitch muscles in rats. Medicina (kaunas) 55:291. https://doi.org/10.3390/medicina55060291
Joseph AM, Adhihetty PJ, Leeuwenburgh C (2016) Beneficial effects of exercise on age-related mitochondrial dysfunction and oxidative stress in skeletal muscle. J Physiol 594:5105–5123. https://doi.org/10.1113/JP270659
Kilic-Erkek O, Kilic-Toprak E, Caliskan S, Ekbic Y, Akbudak IH, Kucukatay V, Bor-Kucukatay M (2016) Detraining reverses exercise-induced improvement in blood pressure associated with decrements of oxidative stress in various tissues in spontaneously hypertensive rats. Mol Cell Biochem 412:209–219. https://doi.org/10.1007/s11010-015-2627-4
Kuk JL, Saunders TJ, Davidson LE, Ross R (2009) Age-related changes in total and regional fat distribution. Ageing Res Rev 8:339–348. https://doi.org/10.1016/j.arr.2009.06.001
Lawler JM, Powers SK, Van Dijk H, Visser T, Kordus MJ, Ji LL (1994) Metabolic and antioxidant enzyme activities in the diaphragm: effects of acute exercise. Respir Physiol 96:139–149. https://doi.org/10.1016/0034-5687(94)90122-8
Lee S, Leone TC, Rogosa L, Rumsey J, Ayala J, Coen PM, Fitts RH, Vega RB, Kelly DP (2017) Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice. Am J Physiol Endocrinol Metab 312:E394–E406. https://doi.org/10.1152/ajpendo.00380.2016
Lemmer JT, Hurlbut DE, Martel GF, Tracy BL, Ivey FM, Metter EJ, Fozard JL, Fleg JL, Hurley BF (2000) Age and gender responses to strength training and detraining. Med Sci Sports Exerc 2000(32):1505–1512. https://doi.org/10.1097/00005768-200008000-00021
Li FH, Li T, Ai JY, Sun L, Min Z, Duan R, Zhu L, Liu YY, Liu TC (2018) Beneficial autophagic activities, mitochondrial function, and metabolic phenotype adaptations promoted by high-intensity interval training in a rat model. Front Physiol 9:571. https://doi.org/10.3389/fphys.2018.00571
Liang J, Zhang H, Zeng Z, Wu L, Zhang Y, Guo Y, Lv J, Wang C, Fan J, Chen N (2021) Lifelong aerobic exercise alleviates sarcopenia by activating autophagy and inhibiting protein degradation via the AMPK/PGC-1α signaling pathway. Metabolites 11:323. https://doi.org/10.3390/metabo11050323
Liang Z, Zhang T, Liu H, Li Z, Peng L, Wang C, Wang T (2022) Inflammaging: the ground for sarcopenia? Exp Gerontol 168:111931. https://doi.org/10.1016/j.exger.2022.111931
Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. https://doi.org/10.2147/CIA.S158513
Lo MS, Lin LL, Yao WJ, Ma MC (2011) Training and detraining effects of the resistance vs. endurance program on body composition, body size, and physical performance in young men. J Strength Cond Res 25:2246–2254. https://doi.org/10.1519/JSC.0b013e3181e8a4be
Lv J, Hou B, Song J, Xu Y, Xie S (2022) The relationship between ferroptosis and diseases. J Multidiscip Healthc 15:2261–2275. https://doi.org/10.2147/JMDH.S382643
Ma S, Sun S, Geng L, Song M, Wang W, Ye Y, Ji Q, Zou Z, Wang S, He X, Li W, Esteban CR, Long X, Guo G, Chan P, Zhou Q, Belmonte JCI, Zhang W, Qu J, Liu GH (2020) Caloric restriction reprograms the single-cell transcriptional landscape of Rattus Norvegicus aging. Cell 180:984–1001. https://doi.org/10.1016/j.cell.2020.02.008
Mikkelsen UR, Couppé C, Karlsen A, Grosset JF, Schjerling P, Mackey AL, Klausen HH, Magnusson SP, Kjær M (2013) Life-long endurance exercise in humans: circulating levels of inflammatory markers and leg muscle size. Mech Ageing Dev 134:531–540. https://doi.org/10.1016/j.mad.2013.11.004
Mora JC, Valencia WM (2018) Exercise and older adults. Clin Geriatr Med 34:145–162. https://doi.org/10.1016/j.cger.2017.08.007
Morinaga M, Sako N, Isobe M, Lee-Hotta S, Sugiura H, Kametaka S (2021) Aerobic exercise ameliorates cancer cachexia-induced muscle wasting through adiponectin signaling. Int J Mol Sci 22:3110. https://doi.org/10.3390/ijms22063110
Mujika I, Padilla S (2000a) Detraining: loss of training-induced physiological and performance adaptations. Part I: short term insufficient training stimulus. Sports Med 30:79–87. https://doi.org/10.2165/00007256-200030020-00002
Mujika I, Padilla S (2000b) Detraining loss of training-induced physiological and performance adaptations. Part II: long term insufficient training stimulus. Sports Med 30:145–154. https://doi.org/10.2165/00007256-200030030-00001
Nalbant O, Toktaş N, Toraman NF, Ogüş C, Aydin H, Kaçar C, Ozkaya YG (2009) Vitamin E and aerobic exercise: effects on physical performance in older adults. Aging Clin Exp Res 21:111–121. https://doi.org/10.1007/BF03325218
Nilsson MI, Bourgeois JM, Nederveen JP, Leite MR, Hettinga BP, Bujak AL, May L, Lin E, Crozier M, Rusiecki DR, Moffatt C, Azzopardi P, Young J, Yang Y, Nguyen J, Adler E, Lan L, Tarnopolsky MA (2019) Lifelong aerobic exercise protects against inflammaging and cancer. PLoS ONE 14:e0210863. https://doi.org/10.1371/journal.pone.0210863
Ponti F, Santoro A, Mercatelli D, Gasperini C, Conte M, Martucci M, Sangiorgi L, Franceschi C, Bazzocchi A (2020) Aging and imaging assessment of body composition: from fat to facts. Front Endocrinol (lausanne) 10:861. https://doi.org/10.3389/fendo.2019.00861
Powers SK, Criswell D, Lawler J, Ji LL, Martin D, Herb RA, Dudley G (1994) Influence of exercise and fiber type on antioxidant enzyme activity in rat skeletal muscle. Am J Physiol 266:R375-380. https://doi.org/10.1152/ajpregu.1994.266.2.R375
Pyo IS, Yun S, Yoon YE, Choi JW, Lee SJ (2020) Mechanisms of aging and the preventive effects of resveratrol on age-related diseases. Molecules 25:464–469. https://doi.org/10.3390/molecules25204649
Qaisar R, Bhaskaran S, Van Remmen H (2016) Muscle fiber type diversification during exercise and regeneration. Free Radic Biol Med 98:56–67. https://doi.org/10.1016/j.freeradbiomed.2016.03.025
Ramez M, Rajabi H, Ramezani F, Naderi N, Darbandi-Azar A, Nasirinezhad F (2019) The greater effect of high-intensity interval training versus moderate-intensity continuous training on cardioprotection against ischemia-reperfusion injury through Klotho levels and attenuate of myocardial TRPC6 expression. BMC Cardiovasc Disord 19(1):118. https://doi.org/10.1186/s12872-019-1090-7
Ren Y, Li Y, Yan J, Ma M, Zhou D, Xue Z, Zhang Z, Liu H, Yang H, Jia L, Zhang L, Zhang Q, Mu S, Zhang R, Da Y (2017) Adiponectin modulates oxidative stress-induced mitophagy and protects C2C12 myoblasts against apoptosis. Sci Rep 7:3209. https://doi.org/10.1038/s41598-017-03319-2
Ruegsegger GN, Booth FW (2018) Health Benefits of Exercise. Cold Spring Harb Perspect Med 8:a029694. https://doi.org/10.1101/cshperspect.a029694
Serrano AL, Quiroz-Rothe E, Rivero JL (2000) Early and long-term changes of equine skeletal muscle in response to endurance training and detraining. Pflugers Arch 441(2–3):263–274. https://doi.org/10.1007/s004240000408
Sertie RAL, Curi R, Oliveira AC, Andreotti S, Caminhotto RO, de Lima TM, Proença ARG, Reis GB, Lima FB (2019) The mechanisms involved in the increased adiposity induced by interruption of regular physical exercise practice. Life Sci 222:103–111. https://doi.org/10.1016/j.lfs.2019.02.051
Singh AK, Shree S, Chattopadhyay S, Kumar S, Gurjar A, Kushwaha S, Kumar H, Trivedi AK, Chattopadhyay N, Maurya R, Ramachandran R, Sanyal S (2017) Small molecule adiponectin receptor agonist GTDF protects against skeletal muscle atrophy. Mol Cell Endocrinol 439:273–285. https://doi.org/10.1016/j.mce.2016.09.013
Sternfeld B, Ngo L, Satariano WA, Tager IB (2002) Associations of body composition with physical performance and self-reported functional limitation in elderly men and women. Am J Epidemiol 156:110–121. https://doi.org/10.1093/aje/kwf023
Sun L, Li FH, Han C, Wang ZZ, Gao KK, Qiao YB, Ma S, Xie T, Wang J (2021) Alterations in mitochondrial biogenesis and respiratory activity, inflammation of the senescence-associated secretory phenotype, and lipolysis in the perirenal fat and liver of rats following lifelong exercise and detraining. FASEB J 35(10):e21890. https://doi.org/10.1096/fj.202100868R
Szentesi P, Csernoch L, Dux L, Keller-Pintér A (2019) Changes in redox signaling in the skeletal muscle with aging. Oxid Med Cell Longev 2019:4617801. https://doi.org/10.1155/2019/4617801
Taaffe DR, Marcus R (1997) Dynamic muscle strength alterations to detraining and retraining in elderly men. Clin Physiol 17:311–324. https://doi.org/10.1111/j.1365-2281.1997.tb00010.x
Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, Khosla S, Jensen MD, Kirkland JL (2010) Fat tissue, aging, and cellular senescence. Aging Cell 9:667–684. https://doi.org/10.1111/j.1474-9726.2010.00608.x
Timmer LT, Hoogaars WMH, Jaspers RT (2018) The role of IGF-1 signaling in skeletal muscle atrophy. Adv Exp Med Biol 1088:109–137. https://doi.org/10.1007/978-981-13-1435-3_6
Toledo-Arruda AC, Sousa Neto IV, Vieira RP, Guarnier FA, Caleman-Neto A, Suehiro CL, Olivo CR, Cecchini R, Prado CM, Lin CJ, Durigan JLQ, Martins MA (2020) Aerobic exercise training attenuates detrimental effects of cigarette smoke exposure on peripheral muscle through stimulation of the Nrf2 pathway and cytokines: a time-course study in mice. Appl Physiol Nutr Metab 45:978–986. https://doi.org/10.1139/apnm-2019-0543
Tonolo F, Folda A, Scalcon V, Marin O, Bindoli A, Rigobello MP (2022) Nrf2-activating bioactive peptides exert anti-inflammatory activity through Inhibition of the NF-κB Pathway. Int J Mol Sci 23:4382. https://doi.org/10.3390/ijms23084382
Toraman NF (2005) Short term and long term detraining: is there any difference between young-old and old people? Br J Sports Med 39:561–564. https://doi.org/10.1136/bjsm.2004.015420
Wang T (2022) Searching for the link between inflammaging and sarcopenia. Ageing Res Rev 77:101611. https://doi.org/10.1016/j.arr.2022.101611
Wang DT, Yin Y, Yang YJ, Lv PJ, Shi Y, Lu L, Wei LB (2014) Resveratrol prevents TNF-α-induced muscle atrophy via regulation of Akt/mTOR/FoxO1 signaling in C2C12 myotubes. Int Immunopharmacol 19:206–213. https://doi.org/10.1016/j.intimp.2014.02.002
Webster JM, Kempen LJAP, Hardy RS, Langen RCJ (2020) Inflammation and skeletal muscle wasting during cachexia. Front Physiol 11:597675. https://doi.org/10.3389/fphys.2020.597675
Yan X, Shen Z, Yu D, Zhao C, Zou H, Ma B, Dong W, Chen W, Huang D, Yu Z (2022) Nrf2 contributes to the benefits of exercise interventions on age-related skeletal muscle disorder via regulating Drp1 stability and mitochondrial fission. Free Radic Biol Med 178:59–75. https://doi.org/10.1016/j.freeradbiomed.2021.11.030
Yang W, Li Y, Wang JY, Han R, Wang L (2018) Circulating levels of adipose tissue-derived inflammatory factors in elderly diabetes patients with carotid atherosclerosis: a retrospective study. Cardiovasc Diabetol 17:75. https://doi.org/10.1186/s12933-018-0723-y
Yoshida T, Delafontaine P (2020) Mechanisms of IGF-1-mediated regulation of skeletal muscle hypertrophy and atrophy. Cells 9:1970. https://doi.org/10.3390/cells9091970
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We would like to thank those who supported this study. We would like to thank Editage (www.editage.cn) for English language editing.
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This work was supported by the National Natural Science Foundation of China [Grant Nos. 31500961 and 31971099] and Interdisciplinary Studies at Nanjing Normal University.
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Z-ZW performed the experiments; H-CX, H-XZ, and C-KZ analyzed the data; B-ML and J-HH interpreted the results of the experiments; Y-QL and P-SN prepared the figures; Z-ZW drafted, edited, and revised the manuscript; F-HL and X-MY conceived and designed the research. All authors read and approved the final manuscript.
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Wang, ZZ., Xu, HC., Zhou, HX. et al. Long-term detraining reverses the improvement of lifelong exercise on skeletal muscle ferroptosis and inflammation in aging rats: fiber-type dependence of the Keap1/Nrf2 pathway. Biogerontology 24, 753–769 (2023). https://doi.org/10.1007/s10522-023-10042-1
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DOI: https://doi.org/10.1007/s10522-023-10042-1