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Nicotinamide riboside (NR), a vitamin B3 precursor to NAD\n                    <jats:sup>+<\/jats:sup>\n                    , and high\u2010intensity interval training (HIIT) have both been proposed to ameliorate aging\u2010related mitochondrial decline, but their effects on skeletal muscle epigenetic aging are not fully elucidated. Here, we assessed the impact of 5\u2010month NR supplementation and 4\u20136\u2009weeks HIIT on epigenetic age acceleration (EAA, via seven epigenetic clocks) in human skeletal muscle across three independent studies. NR supplementation was associated with reduced muscle EAA, particularly when measured with the PCHannum, MEAT, and DunedinPACE clocks, while HIIT produced opposite effects in some clocks, notably increasing pace of aging by DunedinPACE. Correlation analyses revealed that changes in skeletal muscle mitochondrial content correlated with changes in MEAT\u2010derived EAA after NR and 6\u2009weeks of HIIT. Together, these findings indicate that skeletal muscle epigenetic aging can be modulated by NR and HIIT interventions but in opposing directions, highlighting a potential link between mitochondrial abundance and epigenetic clocks. Further studies are warranted to clarify how NR and exercise regulate epigenetic aging. These results offer new insights into development of strategies for promoting epigenetic outcomes and healthy aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.70638","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:10:44Z","timestamp":1784689844000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Divergent Effects of Nicotinamide Riboside and High\u2010Intensity Exercise Training on Skeletal Muscle Epigenetic Aging"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5770-6475","authenticated-orcid":false,"given":"Aino","family":"Heikkinen","sequence":"first","affiliation":[{"name":"Minerva Foundation Institute for Medical Research  Helsinki Finland"},{"name":"Institute for Molecular Medicine Finland (FIMM), HiLIFE University of Helsinki  Helsinki 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K.Haimilahti S.Jansson S.Forsstr\u00f6m J.Buzkova andA.Suomalainen.2025.\u201cDynamics of Blood NAD and Glutathione in Health Disease Aging and Under NAD\u2010Booster Treatment.\u201dbioRxiv 2025.02.24.639825.http:\/\/biorxiv.org\/content\/early\/2025\/02\/28\/2025.02.24.639825.abstract."},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202913"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010018\u20100059\u20104"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13816"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.10.005"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201059576\u20107"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010022\u201000248\u20102"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901997RR"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14962"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/17461391.2022.2048894"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010022\u201000220\u20100"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2012.142"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd12040158"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add5163"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.230185"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3480425"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010026\u201004239\u20103"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010022\u201004088\u2010z"},{"key":"e_1_2_12_29_1","first-page":"9484","article-title":"DNA Methylation GrimAge Version 2","volume":"14","author":"Lu A. 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