{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:27:12Z","timestamp":1786688832827,"version":"build-2736575974"},"reference-count":192,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Aging is fundamentally associated with the gradual accumulation of DNA damage, which is instrumental in the initiation and advancement of age-associated pathologies, including neurodegenerative conditions such as Alzheimer\u2019s disease and Parkinson\u2019s disease. Recent studies indicate that lifestyle modifications\u2014especially the consumption of functional foods and participation in consistent physical exercise\u2014can influence cellular and molecular processes related to DNA repair, reduction of oxidative stress, and maintenance of genomic integrity. This review consolidates contemporary research regarding how particular bioactive compounds (e.g., polyphenols, omega-3 fatty acids, and flavonoids) present in functional foods, in conjunction with diverse exercise interventions, affect DNA repair processes and diminish genotoxic stress. We examine evidence from exercise-only, nutrition-only, and combined lifestyle interventions, with particular attention to whether combined interventions show additive, complementary, or genuinely synergistic effects on oxidative stress, inflammatory responses, epigenetic aging, and DNA repair-related pathways. Particular emphasis is placed on the susceptibility of the brain to DNA damage and the significance of these interventions in safeguarding neuronal integrity and cognitive capabilities. By synthesizing evidence from molecular, animal, and human research, this review underscores the therapeutic promise of functional foods and physical activity as readily available, non-pharmacological approaches to ameliorate genomic integrity and postpone the onset or progression of aging-related and neurodegenerative disorders. In conclusion, we address prevailing limitations, deficiencies in translational research, and prospective avenues for personalized lifestyle medicine aimed at enhancing DNA integrity.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1772217","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:33:02Z","timestamp":1786685582000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise alone or combined with functional foods in aging and age-related diseases: targeting DNA damage, repair pathways, and genome integrity"],"prefix":"10.3389","volume":"18","author":[{"given":"Ying","family":"Ma","sequence":"first","affiliation":[{"name":"School of Sports and Music, Central South University of Forestry and Technology","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physical Education, Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Physical Education, Sangmyung University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongchang","family":"Fan","sequence":"additional","affiliation":[{"name":"Ministry of Sports, Nanjing Railway Vocational and Technical College","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2334","DOI":"10.1096\/fj.09-147991","article-title":"Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane","volume":"24","author":"Aamann","year":"2010","journal-title":"FASEB J."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1016\/j.biocel.2007.04.013","article-title":"Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase\/nuclear factor-kappa B signaling in patients with type 2 diabetes and microangiopathy","volume":"39","author":"Adaikalakoteswari","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cell.2013.01.007","article-title":"Mechanisms of programmed DNA lesions and genomic instability in the immune system","volume":"152","author":"Alt","year":"2013","journal-title":"Cell"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1062832","DOI":"10.3389\/fpubh.2023.1062832","article-title":"The role of resistance training and creatine supplementation on oxidative stress, antioxidant defense, muscle strength, and quality of life in older adults","volume":"11","author":"Amiri","year":"2023","journal-title":"Front. Public Health"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081907","article-title":"Phosphorylation targets of DNA-PK and their role in HIV-1 replication","volume":"9","author":"Anisenko","year":"2020","journal-title":"Cells"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22858-w","article-title":"TDP43 nuclear export and neurodegeneration in models of amyotrophic lateral sclerosis and frontotemporal dementia","volume":"8","author":"Archbold","year":"2018","journal-title":"Sci. Rep."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1111\/bpa.12370","article-title":"Alpha-synuclein as a biomarker for Parkinson's disease","volume":"26","author":"Atik","year":"2016","journal-title":"Brain Pathol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"380","DOI":"10.12965\/jer.1632808.404","article-title":"Role of exercise on the brain","volume":"12","author":"Baek","year":"2016","journal-title":"J Exerc Rehabil."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/ene.14108","article-title":"Parkinson disease","volume":"27","author":"Balestrino","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1126\/science.281.5383.1674","article-title":"Enhanced phosphorylation of p53 by ATM in response to DNA damage","volume":"281","author":"Banin","year":"1998","journal-title":"Science"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1523\/JNEUROSCI.4988-09.2010","article-title":"Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis","volume":"30","author":"Barmada","year":"2010","journal-title":"J. Neurosci."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/s0092-8674(03)00566-x","article-title":"Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors","volume":"114","author":"Bassing","year":"2003","journal-title":"Cell"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/bs.irn.2019.07.002","article-title":"Modulation of synaptic plasticity by exercise","volume":"147","author":"Bettio","year":"2019","journal-title":"Int. Rev. Neurobiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/s43587-024-00793-y","article-title":"Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial","volume":"5","author":"Bischoff-Ferrari","year":"2025","journal-title":"Nat. Aging"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","article-title":"ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response","volume":"66","author":"Blackford","year":"2017","journal-title":"Mol. Cell"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1055\/s-0043-119882","article-title":"Lifelong voluntary exercise modulates age-related changes in oxidative stress","volume":"39","author":"Bouzid","year":"2018","journal-title":"Int. J. Sports Med."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/2041-9414-3-9","article-title":"Pathway choice in DNA double strand break repair: observations of a balancing act","volume":"3","author":"Brandsma","year":"2012","journal-title":"Genome Integr."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00401-011-0932-x","article-title":"Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis","volume":"123","author":"Brettschneider","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1101\/gad.1067403","article-title":"Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance","volume":"17","author":"Brown","year":"2003","journal-title":"Genes Dev."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1146\/annurev-physiol-030212-183653","article-title":"Aging, cellular senescence, and cancer","volume":"75","author":"Campisi","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"678449","DOI":"10.3389\/fphys.2021.678449","article-title":"Dose-response effect of vibratory stimulus on synaptic and muscle plasticity in a middle-aged murine model","volume":"12","author":"Cariati","year":"","journal-title":"Front. Physiol."},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11010082","article-title":"Modulation of synaptic plasticity by vibratory training in young and old mice","volume":"11","author":"Cariati","year":"","journal-title":"Brain Sci."},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3390\/jfmk6040101","article-title":"Hippocampal adaptations to continuous aerobic training: a functional and ultrastructural evaluation in a young murine model","volume":"6","author":"Cariati","year":"","journal-title":"J Funct Morphol Kinesiol."},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.7750\/biodiscovery.2014.11.1","article-title":"DNA damage and mutation. Types of DNA damage","volume":"11","author":"Chakarov","year":"2014","journal-title":"BioDiscovery"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"C1264","DOI":"10.1152\/ajpcell.00416.2019","article-title":"The cellular and molecular basis of in vivo synaptic plasticity in rodents","volume":"318","author":"Cheyne","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"310","DOI":"10.3109\/17482960802566824","article-title":"Prognostic factors in ALS: a critical review","volume":"10","author":"Chio","year":"2009","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/nrn4020","article-title":"Genomic integrity and the ageing brain","volume":"16","author":"Chow","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1038\/s41593-019-0505-1","article-title":"Age-related hyperinsulinemia leads to insulin resistance in neurons and cell-cycle-induced senescence","volume":"22","author":"Chow","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.molcel.2010.09.019","article-title":"The DNA damage response: making it safe to play with knives","volume":"40","author":"Ciccia","year":"2010","journal-title":"Mol. Cell"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1093\/gerona\/61.11.1166","article-title":"Aerobic exercise training increases brain volume in aging humans","volume":"61","author":"Colcombe","year":"2006","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.mrfmmm.2014.11.010","article-title":"DNA damage in neurodegenerative diseases","volume":"776","author":"Copped\u00e8","year":"2015","journal-title":"Mutat. Res."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.neurol.2017.04.001","article-title":"ALS and frontotemporal dementia belong to a common disease spectrum","volume":"173","author":"Couratier","year":"2017","journal-title":"Rev. Neurol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/bs.acc.2017.01.005","article-title":"Physical exercise and DNA injury: good or evil?","volume":"81","author":"Danese","year":"","journal-title":"Adv. Clin. Chem."},{"key":"ref35","first-page":"193","volume-title":"Advances in Clinical Chemistry","author":"Danese","year":""},{"key":"ref36","doi-asserted-by":"publisher","first-page":"57991","DOI":"10.18632\/oncotarget.19854","article-title":"Modulation of GDF11 expression and synaptic plasticity by age and training","volume":"8","author":"De Domenico","year":"2017","journal-title":"Oncotarget"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/8856621","article-title":"Effects of physical exercise on neuroplasticity and brain function: a systematic review in human and animal studies","volume":"2020","author":"de Sousa Fernandes","year":"2020","journal-title":"Neural Plast."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1016\/j.dnarep.2008.03.011","article-title":"Mitochondrial DNA, base excision repair and neurodegeneration","volume":"7","author":"de Souza-Pinto","year":"2008","journal-title":"DNA Repair (Amst)"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1093\/brain\/awy062","article-title":"TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis","volume":"141","author":"Deshaies","year":"2018","journal-title":"Brain"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.tibs.2011.10.002","article-title":"The ATM protein kinase and cellular redox signaling: beyond the DNA damage response","volume":"37","author":"Ditch","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"102640","DOI":"10.1016\/j.redox.2023.102640","article-title":"The influence of vitamin D supplementation and strength training on health biomarkers and chromosomal damage in community-dwelling older adults","volume":"61","author":"Draxler","year":"2023","journal-title":"Redox Biol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1083\/jcb.200905138","article-title":"Mutant huntingtin impairs Ku70-mediated DNA repair","volume":"189","author":"Enokido","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1002\/hipo.20547","article-title":"Aerobic fitness is associated with hippocampal volume in elderly humans","volume":"19","author":"Erickson","year":"2009","journal-title":"Hippocampus"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1073\/pnas.1015950108","article-title":"Exercise training increases size of hippocampus and improves memory","volume":"108","author":"Erickson","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1001\/jamaneurol.2020.4152","article-title":"Burden of neurological disorders across the US from 1990-2017: a global burden of disease study","volume":"78","author":"Feigin","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"7789","DOI":"10.1007\/s12035-018-0947-6","article-title":"Towards a TDP-43-based biomarker for ALS and FTLD","volume":"55","author":"Feneberg","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.neuroimage.2017.11.007","article-title":"Effect of aerobic exercise on hippocampal volume in humans: a systematic review and meta-analysis","volume":"166","author":"Firth","year":"2018","journal-title":"NeuroImage"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"11244","DOI":"10.1093\/nar\/gkaa804","article-title":"Mechanisms of replication and repair in mitochondrial DNA deletion formation","volume":"48","author":"Fontana","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s00401-008-0389-8","article-title":"TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer\u2019s disease and frontotemporal lobar degeneration","volume":"116","author":"Foulds","year":"2008","journal-title":"Acta Neuropathol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1093\/mutage\/geu074","article-title":"The impact of six months strength training, nutritional supplementation or cognitive training on DNA damage in institutionalised elderly","volume":"30","author":"Franzke","year":"","journal-title":"Mutagenesis"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.exger.2015.03.001","article-title":"The effect of six months of elastic band resistance training, nutritional supplementation or cognitive training on chromosomal damage in institutionalized elderly","volume":"65","author":"Franzke","year":"","journal-title":"Exp. Gerontol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.freeradbiomed.2018.04.565","article-title":"Age and the effect of exercise, nutrition and cognitive training on oxidative stress - the Vienna active aging study (VAAS), a randomized controlled trial","volume":"121","author":"Franzke","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1097\/PHM.0b013e31828cd254","article-title":"The beneficial role of intensive exercise on Parkinson disease progression","volume":"92","author":"Frazzitta","year":"2013","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/jnc.14327","article-title":"Pathomechanisms of TDP-43 in neurodegeneration","volume":"146","author":"Gao","year":"2018","journal-title":"J. Neurochem."},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2014.06.004","article-title":"Elite athletes live longer than the general population: a meta-analysis","author":"Garatachea","year":"2014","journal-title":"Mayo Clin. Proc."},{"key":"ref56","doi-asserted-by":"crossref","DOI":"10.1249\/MSS.0b013e318213fefb","volume-title":"Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory, Musculoskeletal, and Neuromotor Fitness in Apparently Healthy Adults: Guidance for Prescribing Exercise","author":"Garber","year":"2011"},{"key":"ref57","volume-title":"The effect of eight weeks Concurrent Training and Supplementation of L-Arginine on plasma level of 8-Hydroxydeoxyguanosine (8-OHdG), Malondialdehyde and Total Antioxidant Capacity in Elderly men (Multivariate longitudinal Modeling)","author":"Gilani","year":"2018"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3390\/life11020153","article-title":"Evidence of the cellular senescence stress response in mitotically active brain cells\u2014implications for cancer and neurodegeneration","volume":"11","author":"Gillispie","year":"2021","journal-title":"Life."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"941868","DOI":"10.1155\/2012\/941868","article-title":"Antioxidant and anti-inflammatory effects of exercise in diabetic patients","volume":"2012","author":"Golbidi","year":"2012","journal-title":"J. Diabetes Res."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.mad.2012.01.005","article-title":"Oxidative genome damage and its repair: implications in aging and neurodegenerative diseases","volume":"133","author":"Hegde","year":"2012","journal-title":"Mech. Ageing Dev."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"10502","DOI":"10.1074\/jbc.TM118.000371","article-title":"How cells ensure correct repair of DNA double-strand breaks","volume":"293","author":"Her","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/35077232","article-title":"Genome maintenance mechanisms for preventing cancer","volume":"411","author":"Hoeijmakers","year":"2001","journal-title":"Nature"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1056\/NEJMra0804615","article-title":"DNA damage, aging, and cancer","volume":"361","author":"Hoeijmakers","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"519","DOI":"10.3892\/br.2016.630","article-title":"Role of oxidative stress in Alzheimer's disease","volume":"4","author":"Huang","year":"2016","journal-title":"Biomedical reports."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1172\/JCI44867","article-title":"Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice","volume":"121","author":"Igaz","year":"2011","journal-title":"J. Clin. Invest."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/s004010100418","article-title":"Expression of 8-oxoguanine DNA glycosylase is reduced and associated with neurofibrillary tangles in Alzheimer's disease brain","volume":"103","author":"Iida","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1136\/jmedgenet-2016-104271","article-title":"Genetics insight into the amyotrophic lateral sclerosis\/frontotemporal dementia spectrum","volume":"54","author":"Ji","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.molcel.2015.02.024","article-title":"Differential phosphorylation of DNA-PKcs regulates the interplay between end-processing and end-ligation during nonhomologous end-joining","volume":"58","author":"Jiang","year":"2015","journal-title":"Mol. Cell"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1159\/000444788","article-title":"Cerebrospinal fluid TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis patients with and without the C9ORF72 hexanucleotide expansion","volume":"6","author":"Junttila","year":"2016","journal-title":"Dementia Geriatric Cognitive Disorders Extra."},{"key":"ref71","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat8407","article-title":"Poly (ADP-ribose) drives pathologic \u03b1-synuclein neurodegeneration in Parkinson\u2019s disease","volume":"362","author":"Kam","year":"2018","journal-title":"Science"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.arr.2017.09.003","article-title":"Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: a meta-analysis","volume":"40","author":"Karssemeijer","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"R1800","DOI":"10.1152\/ajpregu.00805.2004","article-title":"Dorsomedial hypothalamic corticotropin-releasing factor mediation of exercise-induced anorexia","volume":"288","author":"Kawaguchi","year":"2005","journal-title":"Am. J. Phys. Regul. Integr. Comp. Phys."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"111817","DOI":"10.1016\/j.fct.2020.111817","article-title":"Flavonoids targeting NRF2 in neurodegenerative disorders","volume":"146","author":"Khan","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/S0140-6736(10)61156-7","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Kiernan","year":"2011","journal-title":"Lancet"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.physbeh.2010.09.021","article-title":"Treadmill exercise inhibits traumatic brain injury-induced hippocampal apoptosis","volume":"101","author":"Kim","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mad.2009.11.002","article-title":"Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats","volume":"131","author":"Koltai","year":"2010","journal-title":"Mech. Ageing Dev."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"3137","DOI":"10.3390\/ijms19103137","article-title":"The emerging role of DNA damage in the pathogenesis of the C9orf72 repeat expansion in amyotrophic lateral sclerosis","volume":"19","author":"Konopka","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"ref79","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-1-4939-9124-2_6","volume-title":"Alpha-Synuclein: Methods and Protocols","author":"Kruse","year":"2019"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/nrm2514","article-title":"Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer","volume":"9","author":"Lavin","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jphys.2019.11.014","article-title":"Physical exercise attenuates cognitive decline and reduces behavioural problems in people with mild cognitive impairment and dementia: a systematic review","volume":"66","author":"Law","year":"2020","journal-title":"J. Physiother."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.bbrc.2015.04.038","article-title":"Strenuous exercise induces mitochondrial damage in skeletal muscle of old mice","volume":"461","author":"Lee","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"807","DOI":"10.4103\/1673-5374.182709","article-title":"Moderate exercise prevents neurodegeneration in D-galactose-induced aging mice","volume":"11","author":"Li","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/ana.22096","article-title":"Exercise and Alzheimer's disease biomarkers in cognitively normal older adults","volume":"68","author":"Liang","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13041-016-0237-z","article-title":"Altered DNA base excision repair profile in brain tissue and blood in Alzheimer\u2019s disease","volume":"9","author":"Lillenes","year":"2016","journal-title":"Mol. Brain"},{"key":"ref86","volume-title":"Biological Influence of Physical Exercise on Hemostasis. Seminars in Thrombosis and Hemostasis","author":"Lippi","year":"2009"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"5476","DOI":"10.1093\/nar\/gkv472","article-title":"XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage","volume":"43","author":"Liu","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1126\/science.aao4426","article-title":"Aging and neurodegeneration are associated with increased mutations in single human neurons","volume":"359","author":"Lodato","year":"2018","journal-title":"Science"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1126\/science.aab1785","article-title":"Somatic mutation in single human neurons tracks developmental and transcriptional history","volume":"350","author":"Lodato","year":"2015","journal-title":"Science"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"5","DOI":"10.7554\/eLife.21491","article-title":"SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks","volume":"5","author":"Lopez-Mosqueda","year":"2016","journal-title":"eLife"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41591-018-0275-4","article-title":"Exercise-linked FNDC5\/irisin rescues synaptic plasticity and memory defects in Alzheimer's models","volume":"25","author":"Lourenco","year":"2019","journal-title":"Nat. Med."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"7497","DOI":"10.1093\/nar\/gkm821","article-title":"Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer's disease","volume":"35","author":"Lovell","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1038\/ncb2344","article-title":"More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance","volume":"13","author":"Lukas","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.bbr.2016.09.067","article-title":"Physical exercise induces hippocampal neurogenesis and prevents cognitive decline","volume":"317","author":"Ma","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.neuron.2014.06.034","article-title":"DNA damage and its links to neurodegeneration","volume":"83","author":"Madabhushi","year":"2014","journal-title":"Neuron"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1146\/annurev-neuro-090919-022842","article-title":"Synaptic plasticity forms and functions","volume":"43","author":"Magee","year":"2020","journal-title":"Annu. Rev. Neurosci."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12883-018-1091-7","article-title":"TDP-43 as a potential biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis","volume":"18","author":"Majumder","year":"2018","journal-title":"BMC Neurol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"8590578","DOI":"10.1155\/2016\/8590578","article-title":"The role of reactive oxygen species in the pathogenesis of Alzheimer's disease, Parkinson's disease, and Huntington's disease: a Mini review","volume":"2016","author":"Manoharan","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1016\/j.dnarep.2008.06.018","article-title":"Comparison of nonhomologous end joining and homologous recombination in human cells","volume":"7","author":"Mao","year":"2008","journal-title":"DNA Repair (Amst)"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1001\/jamainternmed.2018.4869","article-title":"Effect of exercise intervention on functional decline in very elderly patients during acute hospitalization: a randomized clinical trial","volume":"179","author":"Mart\u00ednez-Velilla","year":"2019","journal-title":"JAMA Intern. Med."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.mad.2015.04.001","article-title":"PARP-1 involvement in neurodegeneration: a focus on Alzheimer\u2019s and Parkinson\u2019s diseases","author":"Martire","year":"2015","journal-title":"Mech. Ageing Dev."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"24731","DOI":"10.1074\/jbc.M113.497974","article-title":"The RNA-binding protein fused in sarcoma (FUS) functions downstream of poly (ADP-ribose) polymerase (PARP) in response to DNA damage","volume":"288","author":"Mastrocola","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1007\/978-3-030-12457-1_38","article-title":"Calcium dynamics and synaptic plasticity","volume":"1131","author":"Mateos-Aparicio","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"6336","DOI":"10.1126\/science.aal1641","article-title":"Intersection of diverse neuronal genomes and neuropsychiatric disease: the brain somatic mosaicism network","volume":"356","author":"McConnell","year":"2017","journal-title":"Science"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/s41419-018-0848-7","article-title":"Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson\u2019s disease","volume":"9","author":"Milanese","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"4696","DOI":"10.1073\/pnas.1818415116","article-title":"Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects","volume":"116","author":"Mitra","year":"2019","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.freeradbiomed.2008.01.002","article-title":"Nucleic acid oxidation in Alzheimer disease","volume":"44","author":"Moreira","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40303-015-0010-8","article-title":"Effects of physical exercise on central nervous system functions: a review of brain region specific adaptations","volume":"3","author":"Morgan","year":"2015","journal-title":"J Molecular Psychiatry"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"601","DOI":"10.5334\/tohm.515","article-title":"Exercise in Huntington\u2019s disease: current state and clinical significance","volume":"9","author":"Mueller","year":"2019","journal-title":"Tremor Other Hyperkinet. Mov."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"e12840","DOI":"10.1111\/acel.12840","article-title":"Tau protein aggregation is associated with cellular senescence in the brain","volume":"17","author":"Musi","year":"2018","journal-title":"Aging Cell"},{"key":"ref112","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071486","article-title":"Chromatin dynamics in genome stability: roles in suppressing endogenous DNA damage and facilitating DNA repair","volume":"18","author":"Nair","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"ref113","volume-title":"Poly (ADP-Ribose) Polymerase-1 Hyperactivation in Neurodegenerative Diseases: The Death knell Tolls for Neurons. Seminars in cell & Developmental Biology","author":"Narne","year":"2017"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/s41467-017-02299-1","article-title":"Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation","volume":"9","author":"Naumann","year":"2018","journal-title":"Nat. Commun."},{"key":"ref115","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084052","article-title":"Molecular mechanisms underlying the beneficial effects of exercise on brain function and neurological disorders","volume":"22","author":"Nay","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.neuroscience.2020.12.013","article-title":"Understanding the neurophysiological and molecular mechanisms of exercise-induced neuroplasticity in cortical and descending motor pathways: where do we stand?","volume":"457","author":"Nicolini","year":"2021","journal-title":"Neuroscience"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1093\/carcin\/22.7.987","article-title":"Base excision repair in a network of defence and tolerance","volume":"22","author":"Nilsen","year":"2001","journal-title":"Carcinogenesis"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3109\/17482968.2010.541263","article-title":"Elevated CSF TDP-43 levels in amyotrophic lateral sclerosis: specificity, sensitivity, and a possible prognostic value","volume":"12","author":"Noto","year":"2011","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref120","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1007\/s00018-009-8737-y","article-title":"DNA repair in mammalian cells: nucleotide excision repair: variations on versatility","volume":"66","author":"Nouspikel","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.neuint.2005.02.009","article-title":"The effects of moderate-, strenuous- and over-training on oxidative stress markers, DNA repair, and memory, in rat brain","volume":"46","author":"Ogonovszky","year":"2005","journal-title":"Neurochem. Int."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1126\/science.1103160","article-title":"Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes","volume":"306","author":"Ozcan","year":"2004","journal-title":"Science"},{"key":"ref123","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8110529","article-title":"Effects of resistance exercise on cerebral redox regulation and cognition: an interplay between muscle and brain","volume":"8","author":"Pinho","year":"2019","journal-title":"Antioxidants (Basel)."},{"key":"ref124","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/981242","article-title":"Physical exercise and redox balance in type 2 diabetics: effects of moderate training on biomarkers of oxidative stress and DNA damage evaluated through comet assay","volume":"2015","author":"Pittaluga","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3109\/10715762.2012.761696","article-title":"Exercise-induced oxidative stress in elderly subjects: the effect of red orange supplementation on the biochemical and cellular response to a single bout of intense physical activity","volume":"47","author":"Pittaluga","year":"2013","journal-title":"Free Radic. Res."},{"key":"ref126","doi-asserted-by":"publisher","DOI":"10.3390\/cells9091969","article-title":"ATM protein kinase: old and new implications in neuronal pathways and brain circuitry","volume":"9","author":"Pizzamiglio","year":"2020","journal-title":"Cells"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1007\/s11064-014-1443-7","article-title":"Withania somnifera alleviates parkinsonian phenotypes by inhibiting apoptotic pathways in dopaminergic neurons","volume":"39","author":"Prakash","year":"2014","journal-title":"Neurochem. Res."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1172\/JCI72723","article-title":"ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects","volume":"124","author":"Qiu","year":"2014","journal-title":"J. Clin. Invest."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/S0024-3205(02)02476-1","article-title":"Marathon running alters the DNA base excision repair in human skeletal muscle","volume":"72","author":"Rad\u00e1k","year":"2003","journal-title":"Life Sci."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.freeradbiomed.2008.10.022","article-title":"Exercise improves import of 8-oxoguanine DNA glycosylase into the mitochondrial matrix of skeletal muscle and enhances the relative activity","volume":"46","author":"Radak","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s00424-002-0918-6","article-title":"Exercise training decreases DNA damage and increases DNA repair and resistance against oxidative stress of proteins in aged rat skeletal muscle","volume":"445","author":"Rad\u00e1k","year":"2002","journal-title":"Pflugers Arch."},{"key":"ref133","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.freeradbiomed.2016.01.024","article-title":"Physical exercise, reactive oxygen species and neuroprotection","volume":"98","author":"Radak","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref134","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1089\/ars.2011.4498","article-title":"Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling","volume":"18","author":"Radak","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref135","doi-asserted-by":"publisher","first-page":"3448","DOI":"10.1519\/JSC.0b013e3182162f2b","article-title":"Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise","volume":"25","author":"Rahimi","year":"2011","journal-title":"J. Strength Cond. Res."},{"key":"ref136","doi-asserted-by":"publisher","first-page":"3075","DOI":"10.1007\/s12035-020-01945-y","article-title":"Mitochondrial dysfunction: a potential therapeutic target to treat Alzheimer's disease","volume":"57","author":"Rai","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref137","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jchemneu.2015.12.002","article-title":"Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced parkinsonian mouse model","volume":"71","author":"Rai","year":"2016","journal-title":"J. Chem. Neuroanat."},{"key":"ref138","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1152\/jappl.2001.90.2.724","article-title":"Invited review: redox modulation of skeletal muscle contraction: what we know and what we don't","volume":"90","author":"Reid","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"ref139","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1126\/science.abb9032","article-title":"Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons","volume":"372","author":"Reid","year":"2021","journal-title":"Science"},{"key":"ref140","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14080937","article-title":"High-intensity interval training as redox medicine: targeting oxidative stress and antioxidant adaptations in Cardiometabolic disease cohorts","volume":"14","author":"Reljic","year":"2025","journal-title":"Antioxidants (Basel)."},{"key":"ref141","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1249\/JSR.0000000000000446","article-title":"Multiple sclerosis and exercise: a literature review","volume":"17","author":"Reynolds","year":"2018","journal-title":"Curr. Sports Med. Rep."},{"key":"ref142","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168814","article-title":"The impact of physical exercise on the circulating levels of BDNF and NT 4\/5: a review","volume":"22","author":"Ribeiro","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref143","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41593-020-00765-6","article-title":"The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing","volume":"24","author":"Rodin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref144","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1136\/bjsports-2018-100328","article-title":"Precision exercise medicine: understanding exercise response variability","volume":"53","author":"Ross","year":"2019","journal-title":"Br. J. Sports Med."},{"key":"ref145","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1589\/jpts.28.450","article-title":"Impact of different running distances on muscle and lymphocyte DNA damage in amateur marathon runners","volume":"28","author":"Ryu","year":"2016","journal-title":"J. Phys. Ther. Sci."},{"key":"ref146","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.freeradbiomed.2007.07.019","article-title":"Production, detection, and adaptive responses to free radicals in exercise","volume":"44","author":"Sachdev","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref147","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1016\/S0891-5849(03)00187-4","article-title":"Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men","volume":"34","author":"Sacheck","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref148","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1001\/jamaneurol.2013.114","article-title":"Incidence and pathology of synucleinopathies and tauopathies related to parkinsonism","volume":"70","author":"Savica","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref149","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.physbeh.2010.02.017","article-title":"Wheel running eliminates high-fat preference and enhances leptin signaling in the ventral tegmental area","volume":"100","author":"Scarpace","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref150","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1001\/jamaneurol.2017.3517","article-title":"Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial","volume":"75","author":"Schenkman","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref151","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1016\/j.celrep.2016.04.071","article-title":"Inefficient DNA repair is an aging-related modifier of Parkinson\u2019s disease","volume":"15","author":"Sepe","year":"2016","journal-title":"Cell Rep."},{"key":"ref152","doi-asserted-by":"publisher","first-page":"714","DOI":"10.3969\/j.issn.1673-5374.2013.08.006","article-title":"Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate","volume":"8","author":"Shahandeh","year":"2013","journal-title":"Neural Regen. Res."},{"key":"ref153","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s40478-019-0723-5","article-title":"Early neuronal accumulation of DNA double strand breaks in Alzheimer's disease","volume":"7","author":"Shanbhag","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref154","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nrc1011","article-title":"ATM and related protein kinases: safeguarding genome integrity","volume":"3","author":"Shiloh","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref155","doi-asserted-by":"publisher","first-page":"7919","DOI":"10.1007\/s12035-024-04074-y","article-title":"Long non-coding RNA ANRIL and its role in the development of age-related diseases","volume":"61","author":"Shou","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref156","doi-asserted-by":"publisher","first-page":"17181","DOI":"10.18632\/oncotarget.24729","article-title":"Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging","volume":"9","author":"Simioni","year":"2018","journal-title":"Oncotarget"},{"key":"ref157","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1111\/nan.12202","article-title":"A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's cognitive function and ageing study ageing brain cohort","volume":"41","author":"Simpson","year":"2015","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref158","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/nan.12252","article-title":"Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology","volume":"42","author":"Simpson","year":"2016","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref159","doi-asserted-by":"publisher","first-page":"33","DOI":"10.2147\/DNND.S445130","article-title":"A comprehensive review and androgen deprivation therapy and its impact on Alzheimer's disease risk in older men with prostate Cancer","volume":"14","author":"Singh","year":"2024","journal-title":"Degener Neurol Neuromuscul Dis."},{"key":"ref160","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1113\/expphysiol.2011.058396","article-title":"Habitual exercise increases resistance of lymphocytes to oxidant-induced DNA damage by upregulating expression of antioxidant and DNA repairing enzymes","volume":"96","author":"Siu","year":"2011","journal-title":"Exp. Physiol."},{"key":"ref161","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/s0925-4439(00)00040-5","article-title":"Oxidative stress in Alzheimer\u2019s disease","volume":"1502","author":"Smith","year":"2000","journal-title":"Biochimica et Biophysica Acta (BBA)-Molecular Basis Disease"},{"key":"ref162","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1037\/0735-7044.113.3.558","article-title":"Brain noradrenergic responses to footshock after chronic activity-wheel running","volume":"113","author":"Soares","year":"1999","journal-title":"Behav. Neurosci."},{"key":"ref163","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1002\/cbf.3134","article-title":"Effects of physical exercise training in DNA damage and repair activity in humans with different genetic polymorphisms of hOGG1 (Ser326Cys)","volume":"33","author":"Soares","year":"2015","journal-title":"Cell Biochem. Funct."},{"key":"ref164","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1111\/j.1474-9726.2010.00583.x","article-title":"Lifestyle impacts on the aging-associated expression of biomarkers of DNA damage and telomere dysfunction in human blood","volume":"9","author":"Song","year":"2010","journal-title":"Aging Cell"},{"key":"ref165","doi-asserted-by":"publisher","first-page":"6030","DOI":"10.1038\/s41598-018-24463-3","article-title":"Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals","volume":"8","author":"Tamaki","year":"2018","journal-title":"Sci. Rep."},{"key":"ref166","doi-asserted-by":"publisher","first-page":"47","DOI":"10.2147\/DNND.S452009","article-title":"Review of Pharmacotherapeutic targets in Alzheimer's disease and its management using traditional medicinal plants","volume":"14","author":"Tripathi","year":"2024","journal-title":"Degener Neurol Neuromuscul Dis."},{"key":"ref167","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1159\/000488589","article-title":"Long-term moderate exercise rescues age-related decline in hippocampal neuronal complexity and memory","volume":"64","author":"Tsai","year":"2018","journal-title":"Gerontology"},{"key":"ref168","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.cell.2017.01.002","article-title":"Endogenous DNA damage as a source of genomic instability in Cancer","volume":"168","author":"Tubbs","year":"2017","journal-title":"Cell"},{"key":"ref169","doi-asserted-by":"publisher","first-page":"261809","DOI":"10.1155\/2015\/261809","article-title":"Physical training regulates mitochondrial parameters and Neuroinflammatory mechanisms in an experimental model of Parkinson's disease","volume":"2015","author":"Tuon","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref170","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/mds.10305","article-title":"Systematic review of incidence studies of Parkinson's disease","volume":"18","author":"Twelves","year":"2003","journal-title":"Mov Disord"},{"key":"ref171","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1093\/aje\/kwg068","article-title":"Incidence of Parkinson\u2019s disease: variation by age, gender, and race\/ethnicity","volume":"157","author":"Van Den Eeden","year":"2003","journal-title":"Am. J. Epidemiol."},{"key":"ref172","doi-asserted-by":"publisher","first-page":"e39693","DOI":"10.1371\/journal.pone.0039693","article-title":"Amplitude of the SCN clock enhanced by the behavioral activity rhythm","volume":"7","author":"van Oosterhout","year":"2012","journal-title":"PLoS One"},{"key":"ref173","doi-asserted-by":"publisher","first-page":"8680","DOI":"10.1523\/JNEUROSCI.1731-05.2005","article-title":"Exercise enhances learning and hippocampal neurogenesis in aged mice","volume":"25","author":"van Praag","year":"2005","journal-title":"J. Neurosci."},{"key":"ref174","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s00335-017-9732-5","article-title":"Inter-individual variation in adaptations to endurance and resistance exercise training: genetic approaches towards understanding a complex phenotype","volume":"29","author":"Vellers","year":"2018","journal-title":"Mamm. Genome"},{"key":"ref175","doi-asserted-by":"publisher","first-page":"446","DOI":"10.3109\/17482968.2012.703208","article-title":"TDP-43 plasma levels are higher in amyotrophic lateral sclerosis","volume":"13","author":"Verstraete","year":"2012","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref176","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3389\/fnins.2016.00026","article-title":"Regulation of neurogenesis by Neurotrophins during adulthood: expected and unexpected roles","volume":"10","author":"Vilar","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref177","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.4103\/1673-5374.282237","article-title":"The role of exercise in brain DNA damage","volume":"15","author":"Vilela","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref178","doi-asserted-by":"publisher","first-page":"7928","DOI":"10.1007\/s12035-016-0272-x","article-title":"Strength and aerobic exercises improve spatial memory in aging rats through stimulating distinct neuroplasticity mechanisms","volume":"54","author":"Vilela","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref179","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.dnarep.2014.03.030","article-title":"Base excision repair: a critical player in many games","volume":"19","author":"Wallace","year":"2014","journal-title":"DNA Repair"},{"key":"ref180","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1038\/sj.cdd.4400938","article-title":"DNA damage and apoptosis","volume":"8","author":"Wang","year":"2001","journal-title":"Cell Deat Differentiation."},{"key":"ref181","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1212\/WNL.0b013e318247caa1","article-title":"Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease","volume":"78","author":"Watabe-Rudolph","year":"2012","journal-title":"Neurology"},{"key":"ref182","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.cell.2015.12.039","article-title":"Long neural genes harbor recurrent DNA break clusters in neural stem\/progenitor cells","volume":"164","author":"Wei","year":"2016","journal-title":"Cell"},{"key":"ref183","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/s41467-023-35988-1","article-title":"SPRTN patient variants cause global-genome DNA-protein crosslink repair defects","volume":"14","author":"Weickert","year":"2023","journal-title":"Nat. Commun."},{"key":"ref184","doi-asserted-by":"publisher","first-page":"e54217","DOI":"10.15252\/embr.202154217","article-title":"Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease","volume":"23","author":"Welch","year":"2022","journal-title":"EMBO Rep."},{"key":"ref185","volume-title":"World Alzheimer Report 2010: the Global economic impact of Dementia","author":"Wimo","year":"2010"},{"key":"ref186","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1172\/JCI67349","article-title":"PRKDC mutations in a SCID patient with profound neurological abnormalities","volume":"123","author":"Woodbine","year":"2013","journal-title":"J. Clin. Invest."},{"key":"ref187","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/s41586-021-03468-5","article-title":"Neuronal enhancers are hotspots for DNA single-strand break repair","volume":"593","author":"Wu","year":"2021","journal-title":"Nature"},{"key":"ref188","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jchemneu.2016.11.009","article-title":"Mucuna pruriens reduces inducible nitric oxide synthase expression in parkinsonian mice model","volume":"80","author":"Yadav","year":"2017","journal-title":"J. Chem. Neuroanat."},{"key":"ref189","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s12017-013-8270-x","article-title":"BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic\/apyrimidinic endonuclease 1","volume":"16","author":"Yang","year":"2014","journal-title":"NeuroMolecular Med."},{"key":"ref190","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1098-2280(1999)33:1<>3.0.co;2-l","article-title":"Human DNA repair systems: an overview","volume":"33","author":"Yu","year":"1999","journal-title":"Environ. Mol. Mutagen."},{"key":"ref191","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/s41593-019-0372-9","article-title":"Senolytic therapy alleviates a\u03b2-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model","volume":"22","author":"Zhang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref192","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1021\/acs.chemrestox.0c00083","article-title":"Mitochondrial DNA damage: prevalence, biological consequence, and emerging pathways","volume":"33","author":"Zhao","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"ref193","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/35044005","article-title":"The DNA damage response: putting checkpoints in perspective","volume":"408","author":"Zhou","year":"2000","journal-title":"Nature"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1772217\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:33:08Z","timestamp":1786685588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1772217\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":192,"alternative-id":["10.3389\/fnagi.2026.1772217"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1772217","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]},"article-number":"1772217"}}