[1] Deweerdt S.Prevention:Activity is the best medicine[J].Nature, 2011, 475(7355):16-17.
[2] Johansson M E, Cameron I G M, Van Der Kolk N M, et al.Aerobic exercise alters brain function and structure in parkinson's disease:A randomized controlled trial[J].Annals of Neurology, 2022, 91(2):203-216.
[3] Valenzuela P L, Castillo-García A, Morales J S, et al.Exercise benefits on Alzheimer's disease:State-of-the-science[J].Ageing Research Reviews, 2020, 62:101108.
[4] Kwak D, Thompson L V J S M, Science H.Frailty:Past, present, and future?[J].Sports Medicine and Health Science, 2021, 3(1):1-10.
[5] Wang Q, Qian L, Chen S H, et al.Post-treatment with an ultra-low dose of NADPH oxidase inhibitor diphenyleneiodonium attenuates disease progression in multiple Parkinson's disease models[J].Brain, 2015, 138(Pt 5):1247-1262.
[6] Ritzel R M, Crapser J, Patel A R, et al.Age-associated resident memory CD8+T cells in the central nervous system are primed to potentiate inflammation after ischemic brain injury[J].Journal of Immunology, 2016, 196(8):3318-3330.
[7] Sung Y H, Kim S C, Hong H P, et al.Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice[J].Life Science, 2012, 91(25/26):1309-1316.
[8] Jensen C S, Bahl J M, Østergaard L B, et al.Exercise as a potential modulator of inflammation in patients with Alzheimer's disease measured in cerebrospinal fluid and plasma[J].Experimental Gerontology, 2019, 121:91-98.
[9] Fang Z H, Lee C H, Seo M K, et al.Effect of treadmill exercise on the BDNF-mediated pathway in the hippocampus of stressed rats[J].Neuroscience research, 2013, 76(4):187-194.
[10] Mee-inta O, Zhao Z W, Kou Y M.Physical exercise inhibits inflammation and microglial activation[J].Cells, 2019, 8(7):691.
[11] Ionescu-Tucker A, Cotman C W.Emerging roles of oxidative stress in brain aging and Alzheimer's disease[J].Neurobiology of Aging, 2021, 107:86-95.
[12] Kuhn H G, Toda T, Gage F H.Adult hippocampal neurogenesis:A Coming-of-age story[J].The Journal of Neuroscience, 2018, 38(49):10401-10410.
[13] Grimm S, Hoehn A, Davies K J, et al.Protein oxidative modifications in the ageing brain:Consequence for the onset of neurodegenerative disease[J].Free Radical research, 2011, 45(1):73-88.
[14] Perluigi M, Di Domenico F, Giorgi A, et al.Redox proteomics in aging rat brain:Involvement of mitochondrial reduced glutathione status and mitochondrial protein oxidation in the aging process[J].Journal of Neuroscience research, 2010, 88(16):3498-3507.
[15] Schmidlin C J, Dodson M B, Madhavan L, et al.Redox regulation by NRF2 in aging and disease[J].Free Radical Biology and Medicine, 2019, 134:702-707.
[16] Cobley J N, Moult P R, Burniston J G, et al.Exercise improves mitochondrial and redox-regulated stress responses in the elderly:Better late than never![J].Biogerontology, 2015, 16(2):249-264.
[17] Mock J T, Chaudhari K, Sidhu A, et al.The influence of vitamins E and C and exercise on brain aging[J].Experimental Gerontology, 2017, 94:69-72.
[18] López-Otín C, Blasco M A, Partridge L, et al.The hallmarks of aging[J].Cell, 2013, 153(6):1194-1217.
[19] Bernal G M, Peterson D A.Neural stem cells as therapeutic agents for age-related brain repair[J].Aging Cell, 2004, 3(6):345-351.
[20] Zhang H, Kim Y, Ro E J, et al.Hippocampal neurogenesis and neural circuit formation in a cuprizone-induced multiple sclerosis mouse model[J].The Journal of Neuroscience, 2020, 40(2):447-458.
[21] Nicaise A M, Willis C M, Crocker S J, et al.Stem cells of the aging brain[J].Frontiers in Aging Neuroscience, 2020, 12:247.
[22] Ren R, Ocampo A, Liu G H, et al.Regulation of stem cell aging by metabolism and epigenetics[J].Cell Metabolism, 2017, 26(3):460-474.
[23] Liu G H, Qu J, Suzuki K, et al.Progressive degeneration of human neural stem cells caused by pathogenic LRRK2[J].Nature, 2012, 491(7425):603-607.
[24] Fu L, Xu X, Ren R, et al.Modeling xeroderma pigmentosum associated neurological pathologies with patientsderived iPSCs[J].Protein Cell, 2016, 7(3):210-221.
[25] Isaev N K, Stelmashook E V, Genrikhs E E.Neurogenesis and brain aging[J].Reviews in the Neurosciences, 2019, 30(6):573-580.
[26] Adusumilli V S, Walker T L, Overall R W, et al.ROS Dynamics delineate functional states of hippocampal neural stem cells and link to their activity-dependent exit from quiescence[J].Cell Stem Cell, 2021, 28(2):300-314.
[27] Kalamakis G, Brüne D, Ravichandran S, et al.Quiescence modulates stem cell maintenance and regenerative capacity in the aging brain[J].Cell, 2019, 176(6):1407-1419.
[28] Ayhan F, Kulkarni A, Berto S, et al.Resolving cellular and molecular diversity along the hippocampal anteriorto-posterior axis in humans[J].Neuron, 2021, 109(13):2091-2105.
[29] Franjic D, Skarica M, Ma S, et al.Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells[J].Neuron, 2021, doi:10.1016/j.neuron.2021.10.036.
[30] D'Angelo M, Antonosante A, Castelli V, et al.PPARs and energy metabolism adaptation during neurogenesis and neuronal maturation[J].International Journal of Molecular Sciences, 2018, doi:10.3390/ijms19071869.
[31] Vieira M S, Santos A K, Vasconcellos R, et al.Neural stem cell differentiation into mature neurons:Mechanisms of regulation and biotechnological applications[J].Biotechnology Advances, 2018, 36(7):1946-1970.
[32] Zhang W, Qu J, Liu G H, et al.The ageing epigenome and its rejuvenation[J].Nature Reviews:Molecular Cell Biology, 2020, 21(3):137-150.
[33] Patel J, Baptiste B A, Kim E, et al.DNA damage and mitochondria in cancer and aging[J].Carcinogenesis, 2020, 41(12):1625-1634.
[34] Gospodinov A, Vaissiere T, Krastev D B, et al.Mammalian Ino80 mediates double-strand break repair through its role in DNA end strand resection[J].Molecular and Cellular Biology, 2011, 31(23):4735-4745.
[35] van der Horst G T, Meira L, Gorgels T G, et al.UVB radiation-induced cancer predisposition in Cockayne syndrome group A (Csa) mutant mice[J].DNA Repair, 2002, 1(2):143-157.
[36] Katyal S, el-Khamisy S F, Russell H R, et al.TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo[J].The Embo Journal, 2007, 26(22):4720-4731.
[37] Pao P C, Patnaik D, Watson L A, et al.HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer's disease[J].Nature Communications, 2020, 11(1):2484.
[38] Harman D.The biologic clock:The mitochondria?[J].Journal of the Amercian Geriatrics Society, 1972, 20(4):145-147.
[39] Jang J Y, Blum A, Liu J, et al.The role of mitochondria in aging[J].The Journal of Clinical Investigation, 2018, 128(9):3662-3670.
[40] Reddy P H.Mitochondrial medicine for aging and neurodegenerative diseases[J].Neuromolecular Medicine, 2008, 10(4):291-315.
[41] Reddy P H.Mitochondrial dysfunction in aging and Alzheimer's disease:Strategies to protect neurons[J].Antioxidants and Redox Signaling, 2007, 9(10):1647-1658.
[42] Reddy P H, Reddy T P.Mitochondria as a therapeutic target for aging and neurodegenerative diseases[J].Current Alzheimer Research, 2011, 8(4):393-409.
[43] Shigenage M K, Hagen T M, Ames B N.Oxidative damage and mitochondrial decay in aging[J].Proceedings of the National Academy of Sciences of the Unites States of America, 1994, 91(23):10771-10778.
[44] Bertoni-Freddari C, Balietti M, Giorgetti B, et al.Selective decline of the metabolic competence of oversized synaptic mitochondria in the old monkey cerebellum[J].Rejuvenation Research, 2008, 11(2):387-391.
[45] Fontana L, Pariridge L, Longo V D.Extending healthy life span-from yeast to humans[J].Science, 2010, 328(5976):321-326.
[46] Sahin E, Depinho R A.Linking functional decline of telomeres, mitochondria and stem cells during ageing[J].Nature, 2010, 464(7288):520-528.
[47] Kumar S, Lombard D B.Finding Ponce de Leon's pill:Challenges in screening for anti-aging molecules[J].F1000Research, 2016, doi:10.12688/f1000research.7821.1.
[48] 高杰, 沈成, 黄新河.衰老的表观遗传调控机制[J].中国生物化学与分子生物学报, 2017, 33(11):1098-1104.
[49] Unnikrishnan A, Freeman W M, Jackson J, et al.The role of DNA methylation in epigenetics of aging[J].Pharmacology Therapeutics, 2019, 195:172-185.
[50] Sellami M, Bragazzi N, Prince M S, et al.Regular, intense exercise training as a healthy aging lifestyle strategy:Preventing DNA damage, telomere shortening and adverse DNA methylation changes over a lifetime[J].Frontiers in Genetics, 2021, 12:652497.
[51] Zhang F F, Cardarelli R, Carroll J, et al.Physical activity and global genomic DNA methylation in a cancerfree population[J].Epigenetics, 2011, 6(3):293-299.
[52] Nakajima K, Takeoka M, Mori M, et al.Exercise effects on methylation of ASC gene[J].International Journal of Sports Medicine, 2010, 31(9):671-675.
[53] Barrès R, Yan J, Egan B, et al.Acute exercise remodels promoter methylation in human skeletal muscle[J].Cell Metabolism, 2012, 15(3):405-411.
[54] De Meireles L C, Bertoldi K, Cechinel L R, et al.Treadmill exercise induces selective changes in hippocampal histone acetylation during the aging process in rats[J].Neuroscience Letters, 2016, 634:19-24.
[55] De Meireles L C F, Galvão F Jr, Walker D M, et al.Exercise modalities improve aversive memory and survival rate in aged rats:Role of hippocampal epigenetic modifications[J].Molecular Neurobiology, 2019, 56(12):8408-8419.
[56] Fraga I, Weber C, Galiano W B, et al.Effects of a multimodal exercise protocol on functional outcomes, epigenetic modulation and brain-derived neurotrophic factor levels in institutionalized older adults:A quasi-experimental pilot study[J].Neural Regeneration Research, 2021, 16(12):2479-2485.
[57] Grillari J, Hackl M, Grillari-Voglauer R.miR-17-92 cluster:Ups and downs in cancer and aging[J].Biogerontology, 2010, 11(4):501-506.
[58] Menghini R, Casagraned V, Cardellini M, et al.MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1[J].Circulation, 2009, 120(15):1524-1532.
[59] Hu Z, Klein J D, Mitch W E, et al.MicroRNA-29 induces cellular senescence in aging muscle through multiple signaling pathways[J].Aging(Albany NY), 2014, 6(3):160-175.
[60] Guo Y, Li P, Gao L, et al.Kallistatin reduces vascular senescence and aging by regulating microRNA-34aSIRT1 pathway[J].Aging Cell, 2017, 16(4):837-846.
[61] Zeng Z, Liu Y, Zheng W, et al.MicroRNA-129-5p alleviates nerve injury and inflammatory response of Alzheimer's disease via downregulating SOX6[J].Cell Cycle, 2019, 18(22):3095-3110.
[62] Li Z, Chen Q, Liu J, et al.Physical exercise ameliorates the cognitive function and attenuates the neuroinflammation of Alzheimer's disease via miR-129-5p[J].Dementia and Geriatric Cognitive Disorders, 2020, 49(2):163-169.
[63] Yoon J H, Abdelmohsen K, Gorospe M.Posttranscriptional gene regulation by long noncoding RNA[J].Journal of Molecular Biology, 2013, 425(19):3723-3730.
[64] He Y, Qiang Y.Mechanism of autonomic exercise improving cognitive function of Alzheimer's disease by regulating lncRNA SNHG14[J].American Journal of Alzheimer's Disease and Other Dementias, 2021, 36:15333175211027681.
[65] Modarresi F, Pedran Fatemi R, Razavipour S F, et al.A novel knockout mouse model of the noncoding antisense Brain-Derived Neurotrophic Factor (BDNF) gene displays increased endogenous BDNF protein and improved memory function following exercise[J].Heliyon, 2021, 7(7):e07570.
[66] D'anca M, Fenoglio C, Serpente M, et al.Exosome determinants of physiological aging and age-related neurodegenerative diseases[J].Frontiers in Aging Neuroscience, 2019, 11:232.
[67] Soria F N, Pampliega O, Bourdenx M, et al.Exosomes, an unmasked culprit in neurodegenerative diseases[J].Frontiers Neuroscience, 2017, 11:26.
[68] Xu D, Tahara H.The role of exosomes and microRNAs in senescence and aging[J].Advanced Drug Delivery Reviews, 2013, 65(3):368-375.
[69] Sun F, Fu H, Liu Q, et al.Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest[J].FEBS Letters, 2008, 582(10):1564-1568.
[70] Xu D, Takeshita F, Hino Y, et al.miR-22 represses cancer progression by inducing cellular senescence[J].The Journal of Cell Biology, 2011, 193(2):409-424.
[71] Nair V D, Ge Y, Li S, et al.Sedentary and trained older men have distinct circulating exosomal microRNA Profiles at baseline and in response to acute exercise[J].Frontiers in Physiology, 2020, 11:605.
[72] Chaturvedi P, Kalani A, Medina I, et al.Cardiosome mediated regulation of MMP9 in diabetic heart:Role of mir29b and mir455 in exercise[J].Journal of Cellular and Molecular Medicine, 2015, 19(9):2153-2161.
[73] Frühbeis C, Helmig S, Tug S, et al.Physical exercise induces rapid release of small extracellular vesicles into the circulation[J].Journal of Extracellular Vesicles, 2015, 4:28239.
[74] Yang X, Yu D, Xue L, et al.Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice[J].Acta Pharmaceutica Sinica B, 2020, 10(3):475-487.
[75] Yoshimoto S, Mitsuyama E, Yoshida K, et al.Enriched metabolites that potentially promote age-associated diseases in subjects with an elderly-type gut microbiota[J].Gut Microbes, 2021, 13(1):1-11.
[76] Boehme M, Guzzetta K E, Bastiaanssen T F, et al.Microbiota from young mice counteracts selective age-associated behavioral deficits[J].Nature Aging, 2021, 1(8):666-676.
[77] Xia W J, Xu M L, Yu X J, et al.Antihypertensive effects of exercise involve reshaping of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rat[J].Gut Microbes, 2021, 13(1):1-24.
[78] Mcfadzean R.Exercise can help modulate human gut microbiota[J/OL].[2022-01-12].https://scholar.colorado.edu/concern/undergraduate_honors_theses/m613mx95s.
[79] Clauss M, Gérard P, Mosca A, et al.Interplay between exercise and gut microbiome in the context of human health and performance[J].Frontiers in Nutrition, 2021, 8:637010.
[80] Kim B, Elzinga S E, Henn R E, et al.The effects of insulin and insulin-like growth factor I on amyloid precursor protein phosphorylation in in vitro and in vivo models of Alzheimer's disease[J].Neurobiology of Disease, 2019, 132:104541.
[81] Chennaoui M, Léger D, Gomez-merino D.Sleep and the GH/IGF-1 axis:Consequences and countermeasures of sleep loss/disorders[J].Sleep Medicine Reviews, 2020, 49:101223.
[82] Gleeson M, Bishop N C, Stensel D J, et al.The anti-inflammatory effects of exercise:Mechanisms and implications for the prevention and treatment of disease[J].Nature Reviews Immunology, 2011, 11(9):607-615.
[83] Horowitz A M, Fan X, Bieri G, et al.Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain[J].Science, 2020, 369(6500):167-173.
[84] Townsend L K, Macpherson R E K, Wright D C.New horizon:Exercise and a focus on tissue-brain crosstalk[J].The Journal of Clinical Endocrinology Metabolism, 2021, 106(8):2147-2163.
[85] Lourenco M V, Frozza R L, De Freitas G B, et al.Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models[J].Nature Medicine, 2019, 25(1):165-175.
[86] Pignataro P, Dicarlo M, Zerlotin R, et al.FNDC5/Irisin system in neuroinflammation and neurodegenerative diseases:Update and novel perspective[J].International Journal Molecular Sciences, 2021, doi:10.3390/ijms22041605.
[87] Conboy I M, Conboy M J, Wagers A J, et al.Rejuvenation of aged progenitor cells by exposure to a young systemic environment[J].Nature, 2005, 433(7027):760-764.
[88] Mccay C M, Pope F, Lunsford W, et al.Parabiosis between old and young rats[J].Gerontologia, 1957, 1(1):7-17.
[89] Middeldorp J, Lehallier B, Villeda S A, et al.Preclinical assessment of young blood plasma for Alzheimer disease[J].JAMA Neurology, 2016, 73(11):1325-1333.
[90] De Miguel Z, Khoury N, Betley M J, et al.Exercise plasma boosts memory and dampens brain inflammation via clusterin[J].Nature, 2021, 600(7889):494-499.
[91] Li X, Wang L, Zhang S, et al.Timing-Dependent Protection of Swimming:Exercise against d-Galactose-Induced Aging-Like Impairments in Spatial Learning/Memory in Rats[J].Brain Science, 2019, 9(9):236.
[92] Villeda S A, Plambeck K E, Middeldorp J, et al.Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice[J].Nature Medicine, 2014, 20(6):659-663.
[93] 王权, 王铸, 张振, 等.单细胞测序的技术概述[J].中国医药导刊, 2020, 22:7.
[94] Kan M, Shumyatcher M, Himes B E.Using omics approaches to understand pulmonary diseases[J].Respiratory Research, 2017, 18(1):1-20.
[95] 崔凯, 吴伟伟, 刁其玉.转录组测序技术的研究和应用进展[J].生物技术通报, 2019, 35(7):1-9.
[96] Lee M, Cho H S, Yoon K J, et al.Exercise-induced changes of gene expression in the cerebellum of aged mice[J].Biochemical and Biophysical Research Communications, 2020, 521(4):952-956.
[97] Sanfilippo C, Musumeci G, Castrogiobanni P, et al.Hippocampal transcriptome deconvolution reveals differences in cell architecture of not demented elderly subjects underwent late-life physical activity[J].Journal of Chemical Neuroanatomy, 2021, 113:101934.