{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:21:18Z","timestamp":1790990478141,"version":"4.1.0"},"reference-count":160,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"#NEXTGENERATIONEU (NGEU)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Ministry of University and Research (MUR)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"National Recovery and Resilience Plan (NRRP)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"MNESYS","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging is a complex physiological process that profoundly affects the functionality of the musculoskeletal system, contributing to an increase in the incidence of diseases such as osteoporosis, osteoarthritis, and sarcopenia. Cellular senescence plays a crucial role in these degenerative processes, promoting chronic inflammation and tissue dysfunction through the senescence-associated secretory phenotype (SASP). Recently, senotherapeutics have shown promising results in improving musculoskeletal health. Natural compounds such as resveratrol, rapamycin, quercetin, curcumin, vitamin E, genistein, fisetin, and epicatechin act on key signaling pathways, offering protective effects against musculoskeletal decline. On the other hand, molecules such as dasatinib, navitoclax, UBX0101, panobinostat, and metformin have been shown to be effective in eliminating or modulating senescent cells. However, understanding the mechanisms of action, long-term safety, and bioavailability remain areas for further investigation. In this context, physical exercise emerges as an effective non-pharmacological countermeasure, capable of directly modulating cellular senescence and promoting tissue regeneration, representing an integrated strategy to combat age-related diseases. Therefore, we have provided an overview of the main anti-aging compounds and examined the potential of physical exercise as a strategy in the management of age-related musculoskeletal disorders. Further studies should focus on identifying synergistic combinations of pharmacological and non-pharmacological interventions to optimize the effectiveness of anti-aging strategies and promoting healthier musculoskeletal aging.<\/jats:p>","DOI":"10.3390\/ijms26157573","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2796-1721","authenticated-orcid":false,"given":"Angela","family":"Falvino","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, \u201cTor Vergata\u201d University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7174-0714","authenticated-orcid":false,"given":"Roberto","family":"Bonanni","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0330-2189","authenticated-orcid":false,"given":"Umberto","family":"Tarantino","sequence":"additional","affiliation":[{"name":"Catholic University \u201cOur Lady of Good Counsel\u201d, 1000 Tirana, Albania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4779-2212","authenticated-orcid":false,"given":"Virginia","family":"Tancredi","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, \u201cTor Vergata\u201d University of Rome, 00133 Rome, Italy"},{"name":"Centre of Space Bio-Medicine, \u201cTor Vergata\u201d University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2102-5034","authenticated-orcid":false,"given":"Ida","family":"Cariati","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, \u201cTor Vergata\u201d University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1111\/febs.16350","article-title":"Targeting Cellular Senescence with Senotherapeutics: Senolytics and Senomorphics","volume":"290","author":"Zhang","year":"2023","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cariati, I., Scimeca, M., Bonanni, R., Triolo, R., Naldi, V., Toro, G., Marini, M., Tancredi, V., Iundusi, R., and Gasbarra, E. (2022). Role of Myostatin in Muscle Degeneration by Random Positioning Machine Exposure: An in Vitro Study for the Treatment of Sarcopenia. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.782000"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1007\/s00198-022-06482-z","article-title":"Gaps and Alternative Surgical and Non-Surgical Approaches in the Bone Fragility Management: An Updated Review","volume":"33","author":"Tarantino","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mavrogonatou, E., and Kletsas, D. (2024). Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging. Metabolites, 14.","DOI":"10.3390\/metabo14030146"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1101\/gad.343129.120","article-title":"Senescence and the SASP: Many Therapeutic Avenues","volume":"34","author":"Birch","year":"2020","journal-title":"Genes Dev."},{"key":"ref_6","first-page":"13","article-title":"Repurpose Dasatinib and Quercetin: Targeting Senescent Cells Ameliorates Postmenopausal Osteoporosis and Rejuvenates Bone Regeneration","volume":"25","author":"Wang","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sharma, A.K., Roberts, R.L., Benson, R.D.J., Pierce, J.L., Yu, K., Hamrick, M.W., and McGee-Lawrence, M.E. (2020). The Senolytic Drug Navitoclax (ABT-263) Causes Trabecular Bone Loss and Impaired Osteoprogenitor Function in Aged Mice. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00354"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e13979","DOI":"10.1111\/acel.13979","article-title":"Senolytic Treatment Reduces Oxidative Protein Stress in an Aging Male Murine Model of Post-Traumatic Osteoarthritis","volume":"22","author":"Chin","year":"2023","journal-title":"Aging Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1038\/s41467-022-29714-6","article-title":"Distinct and Additive Effects of Calorie Restriction and Rapamycin in Aging Skeletal Muscle","volume":"13","author":"Ham","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Receno, C.N., Liang, C., Korol, D.L., Atalay, M., Heffernan, K.S., Brutsaert, T.D., and DeRuisseau, K.C. (2019). Effects of Prolonged Dietary Curcumin Exposure on Skeletal Muscle Biochemical and Functional Responses of Aged Male Rats. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051178"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Falvino, A., Gasperini, B., Cariati, I., Bonanni, R., Chiavoghilefu, A., Gasbarra, E., Botta, A., Tancredi, V., and Tarantino, U. (2024). Cellular Senescence: The Driving Force of Musculoskeletal Diseases. Biomedicines, 12.","DOI":"10.3390\/biomedicines12091948"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117422","DOI":"10.1016\/j.lfs.2020.117422","article-title":"Resveratrol Promotes Osteogenesis via Activating SIRT1\/FoxO1 Pathway in Osteoporosis Mice","volume":"246","author":"Jiang","year":"2020","journal-title":"Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5572754","DOI":"10.1155\/2023\/5572754","article-title":"The Senolytic Drug Fisetin Attenuates Bone Degeneration in the Zmpste24(\u2212\/\u2212) Progeria Mouse Model","volume":"2023","author":"Hambright","year":"2023","journal-title":"J. Osteoporos."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Li, M., Yu, Y., Xue, K., Li, J., Son, G., Wang, J., Qian, W., Wang, S., Zheng, J., and Yang, C. (2023). Genistein Mitigates Senescence of Bone Marrow Mesenchymal Stem Cells via ERR\u03b1-Mediated Mitochondrial Biogenesis and Mitophagy in Ovariectomized Rats. Redox Biol., 61.","DOI":"10.1016\/j.redox.2023.102649"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/ard-2021-221269","article-title":"Targeting FoxO Transcription Factors with HDAC Inhibitors for the Treatment of Osteoarthritis","volume":"82","author":"Ohzono","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bang, S., Kim, D.-E., Kang, H.-T., and Lee, J.H. (2024). Metformin Restores Autophagic Flux and Mitochondrial Function in Late Passage Myoblast to Impede Age-Related Muscle Loss. Biomed. Pharmacother., 180.","DOI":"10.1016\/j.biopha.2024.116981"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bone.2019.01.015","article-title":"Cellular Senescence in Bone","volume":"121","author":"Farr","year":"2019","journal-title":"Bone"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102275","DOI":"10.1016\/j.arr.2024.102275","article-title":"Senolytic Therapeutics: An Emerging Treatment Modality for Osteoarthritis","volume":"96","author":"Ansari","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1089\/rej.2014.1623","article-title":"Exercise Attenuates the Major Hallmarks of Aging","volume":"18","author":"Garatachea","year":"2015","journal-title":"Rejuvenation Res."},{"key":"ref_20","first-page":"330","article-title":"Effects of Short-Term Aerobic Exercise in a Mouse Model of Niemann-Pick Type C Disease on Synaptic and Muscle Plasticity","volume":"55","author":"Palmieri","year":"2019","journal-title":"Ann. Ist. Super. Sanita"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cariati, I., Bonanni, R., Pallone, G., Scimeca, M., Frank, C., Tancredi, V., and D\u2019Arcangelo, G. (2021). Hippocampal Adaptations to Continuous Aerobic Training: A Functional and Ultrastructural Evaluation in a Young Murine Model. J. Funct. Morphol. Kinesiol., 6.","DOI":"10.3390\/jfmk6040101"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/jbmr.4484","article-title":"STAT3 Hyperactivation Due to SOCS3 Deletion in Murine Osteocytes Accentuates Responses to Exercise- and Load-Induced Bone Formation","volume":"37","author":"McGregor","year":"2022","journal-title":"J. Bone Miner. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.bone.2019.02.006","article-title":"Senescent and Apoptotic Osteocytes and Aging: Exercise to the Rescue?","volume":"121","author":"Sherk","year":"2019","journal-title":"Bone"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.bbrc.2019.03.086","article-title":"Exercise-Induced AMPK Activation Is Involved in Delay of Skeletal Muscle Senescence","volume":"512","author":"Yoon","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Falvino, A., Bonanni, R., Gasperini, B., Cariati, I., Chiavoghilefu, A., Smakaj, A., Visconti, V.V., Botta, A., Iundusi, R., and Gasbarra, E. (2025). Altered Expression of Cell Cycle Regulators and Factors Released by Aged Cells in Skeletal Muscle of Patients with Bone Fragility: A Pilot Study on the Potential Role of SIRT1 in Muscle Atrophy. Biomedicines, 13.","DOI":"10.3390\/biomedicines13061350"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e13415","DOI":"10.1111\/acel.13415","article-title":"Exercise Reduces Circulating Biomarkers of Cellular Senescence in Humans","volume":"20","author":"Englund","year":"2021","journal-title":"Aging Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.arr.2018.05.001","article-title":"Anti-Senescence Compounds: A Potential Nutraceutical Approach to Healthy Aging","volume":"46","author":"Baldoni","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mechchate, H., El Allam, A., El Omari, N., El Hachlafi, N., Shariati, M.A., Wilairatana, P., Mubarak, M.S., and Bouyahya, A. (2022). Vegetables and Their Bioactive Compounds as Anti-Aging Drugs. Molecules, 27.","DOI":"10.3390\/molecules27072316"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/nyas.12145","article-title":"Osteogenic Effects of Resveratrol in Vitro: Potential for the Prevention and Treatment of Osteoporosis","volume":"1290","author":"Mobasheri","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jphs.2023.04.001","article-title":"Resveratrol, a SIRT1 Activator, Attenuates Aging-Associated Alterations in Skeletal Muscle and Heart in Mice","volume":"152","author":"Hosoda","year":"2023","journal-title":"J. Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111215","DOI":"10.1016\/j.mad.2020.111215","article-title":"SIRT1 and Aging Related Signaling Pathways","volume":"187","author":"Chen","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12943-017-0648-1","article-title":"ROS Signaling under Metabolic Stress: Cross-Talk between AMPK and AKT Pathway","volume":"16","author":"Zhao","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1002\/jbmr.460","article-title":"Resveratrol Promotes Osteogenesis of Human Mesenchymal Stem Cells by Upregulating RUNX2 Gene Expression via the SIRT1\/FOXO3A Axis","volume":"26","author":"Tseng","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000151744","article-title":"Activation of Sirt1 Decreases Adipocyte Formation during Osteoblast Differentiation of Mesenchymal Stem Cells","volume":"189","author":"Li","year":"2009","journal-title":"Cells Tissues Organs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1753-4887.2008.00109.x","article-title":"Resveratrol and Novel Potent Activators of SIRT1: Effects on Aging and Age-Related Diseases","volume":"66","author":"Knutson","year":"2008","journal-title":"Nutr. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1080\/13510002.2019.1658376","article-title":"Resveratrol Improves Osteogenic Differentiation of Senescent Bone Mesenchymal Stem Cells through Inhibiting Endogenous Reactive Oxygen Species Production via AMPK Activation","volume":"24","author":"Zhou","year":"2019","journal-title":"Redox Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.exger.2017.08.032","article-title":"The Effect of Exercise, Resveratrol or Their Combination on Sarcopenia in Aged Rats via Regulation of AMPK\/Sirt1 Pathway","volume":"98","author":"Liao","year":"2017","journal-title":"Exp. Gerontol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1007\/s11357-020-00274-1","article-title":"Effect of Rapamycin on Aging and Age-Related Diseases-Past and Future","volume":"43","author":"Selvarani","year":"2021","journal-title":"GeroScience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.clnesp.2021.06.025","article-title":"The Effects of Glucagon and the Target of Rapamycin (TOR) on Skeletal Muscle Protein Synthesis and Age-Dependent Sarcopenia in Humans","volume":"44","year":"2021","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.18632\/aging.102176","article-title":"Rapamycin Protects Aging Muscle","volume":"11","author":"Tang","year":"2019","journal-title":"Aging"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"a025924","DOI":"10.1101\/cshperspect.a025924","article-title":"Inhibition of the Mechanistic Target of Rapamycin (MTOR)-Rapamycin and Beyond","volume":"6","author":"Lamming","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e12943","DOI":"10.1111\/acel.12943","article-title":"MTORC1 Underlies Age-Related Muscle Fiber Damage and Loss by Inducing Oxidative Stress and Catabolism","volume":"18","author":"Tang","year":"2019","journal-title":"Aging Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"111516","DOI":"10.1016\/j.exger.2021.111516","article-title":"Rapamycin Impairs Bone Accrual in Young Adult Mice Independent of Nrf2","volume":"154","author":"Martin","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dhanabalan, K.M., Dravid, A.A., Agarwal, S., Sharath, R.K., Padmanabhan, A.K., and Agarwal, R. (2023). Intra-Articular Injection of Rapamycin Microparticles Prevent Senescence and Effectively Treat Osteoarthritis. Bioeng. Transl. Med., 8.","DOI":"10.1002\/btm2.10298"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-7847.194044","article-title":"Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid","volume":"10","author":"Arulmoli","year":"2016","journal-title":"Pharmacogn. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Chin, K.-Y., and Ima-Nirwana, S. (2020). Quercetin as an Agent for Protecting the Bone: A Review of the Current Evidence. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176448"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/j.biopha.2018.05.003","article-title":"Quercetin Attenuates Mitochondrial Dysfunction and Biogenesis via Upregulated AMPK\/SIRT1 Signaling Pathway in OA Rats","volume":"103","author":"Qiu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_48","first-page":"521","article-title":"Quercetin, a Potent Suppressor of NF-\u039aB and Smad Activation in Osteoblasts","volume":"28","author":"Yamaguchi","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s11914-024-00868-0","article-title":"Quercetin in Osteoporosis Treatment: A Comprehensive Review of Its Mechanisms and Therapeutic Potential","volume":"22","author":"Feng","year":"2024","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_50","first-page":"4313","article-title":"Quercetin Rescued TNF-Alpha-Induced Impairments in Bone Marrow-Derived Mesenchymal Stem Cell Osteogenesis and Improved Osteoporosis in Rats","volume":"10","author":"Yuan","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Wu, Y., Jiang, X., Zhang, X., Xia, L., Lin, K., and Xu, Y. (2015). The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129605"},{"key":"ref_52","first-page":"1414","article-title":"Therapeutic Potential of Quercetin as an Antioxidant for Bone-Muscle-Tendon Regeneration and Aging","volume":"16","author":"Kim","year":"2024","journal-title":"Aging Dis."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hour, T.-C., Vo, T.C.T., Chuu, C.-P., Chang, H.-W., Su, Y.-F., Chen, C.-H., and Chen, Y.-K. (2022). The Promotion of Migration and Myogenic Differentiation in Skeletal Muscle Cells by Quercetin and Underlying Mechanisms. Nutrients, 14.","DOI":"10.3390\/nu14194106"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chen, S., Liang, H., Ji, Y., Kou, H., Zhang, C., Shang, G., Shang, C., Song, Z., Yang, L., and Liu, L. (2021). Curcumin Modulates the Crosstalk Between Macrophages and Bone Mesenchymal Stem Cells to Ameliorate Osteogenesis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.634650"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"914853","DOI":"10.1155\/2014\/914853","article-title":"Vitamin E in Sarcopenia: Current Evidences on Its Role in Prevention and Treatment","volume":"2014","author":"Khor","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/ncomms1594","article-title":"Promotion of Plasma Membrane Repair by Vitamin E","volume":"2","author":"Howard","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"978101","DOI":"10.1155\/2013\/978101","article-title":"Reversal of Myoblast Aging by Tocotrienol Rich Fraction Posttreatment","volume":"2013","author":"Lim","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3868305","DOI":"10.1155\/2017\/3868305","article-title":"Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts","volume":"2017","author":"Khor","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3268136","DOI":"10.1155\/2021\/3268136","article-title":"Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits","volume":"2021","author":"Quispe","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.intimp.2017.02.009","article-title":"Fisetin Inhibits IL-1\u03b2-Induced Inflammatory Response in Human Osteoarthritis Chondrocytes through Activating SIRT1 and Attenuates the Progression of Osteoarthritis in Mice","volume":"45","author":"Zheng","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1039\/D3FO04004F","article-title":"Restorative Effects of (+)-Epicatechin in a Rodent Model of Aging Induced Muscle Atrophy: Underlying Mechanisms","volume":"15","author":"Ramirez","year":"2024","journal-title":"Food Funct."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/acel.12344","article-title":"The Achilles\u2019 Heel of Senescent Cells: From Transcriptome to Senolytic Drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e13275","DOI":"10.1111\/cpr.13275","article-title":"The PI3K\/AKT Signalling Pathway in Inflammation, Cell Death and Glial Scar Formation after Traumatic Spinal Cord Injury: Mechanisms and Therapeutic Opportunities","volume":"55","author":"He","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.spinee.2024.09.017","article-title":"Senolytics Cocktail Dasatinib and Quercetin Alleviate Chondrocyte Senescence and Facet Joint Osteoarthritis in Mice","volume":"25","author":"Zhao","year":"2025","journal-title":"Spine J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1111\/jcmm.17319","article-title":"Targeted Regulation of FoxO1 in Chondrocytes Prevents Age-Related Osteoarthritis via Autophagy Mechanism","volume":"26","author":"Yue","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"970","DOI":"10.14336\/AD.2021.1213","article-title":"Metformin\u2019s Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease","volume":"13","author":"Cheng","year":"2022","journal-title":"Aging Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.1002\/jcb.23206","article-title":"Metformin Stimulates Osteoprotegerin and Reduces RANKL Expression in Osteoblasts and Ovariectomized Rats","volume":"112","author":"Mai","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Wang, C., Yao, Z., Zhang, Y., Yang, Y., Liu, J., Shi, Y., and Zhang, C. (2020). Metformin Mitigates Cartilage Degradation by Activating AMPK\/SIRT1-Mediated Autophagy in a Mouse Osteoarthritis Model. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01114"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e13294","DOI":"10.1111\/acel.13294","article-title":"Is Exercise a Senolytic Medicine? A Systematic Review","volume":"20","author":"Chen","year":"2021","journal-title":"Aging Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7239639","DOI":"10.1155\/2016\/7239639","article-title":"Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases","volume":"2016","author":"Sallam","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1249\/JES.0000000000000302","article-title":"Exercise Counters the Age-Related Accumulation of Senescent Cells","volume":"50","author":"Zhang","year":"2022","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cger.2017.08.007","article-title":"Exercise and Older Adults","volume":"34","author":"Mora","year":"2018","journal-title":"Clin. Geriatr. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1146\/annurev-physiol-060721-095517","article-title":"AMPK and the Adaptation to Exercise","volume":"84","author":"Spaulding","year":"2022","journal-title":"Annu. Rev. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"E308","DOI":"10.1152\/ajpendo.00054.2012","article-title":"NAD+\/NADH and Skeletal Muscle Mitochondrial Adaptations to Exercise","volume":"303","author":"White","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1515\/jbcpp-2021-0308","article-title":"AICAR Promotes Endothelium-Independent Vasorelaxation by Activating AMP-Activated Protein Kinase via Increased ZMP and Decreased ATP\/ADP Ratio in Aortic Smooth Muscle","volume":"33","author":"Pyla","year":"2022","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"17475","DOI":"10.18632\/oncotarget.15728","article-title":"Spermidine Coupled with Exercise Rescues Skeletal Muscle Atrophy from D-Gal-Induced Aging Rats through Enhanced Autophagy and Reduced Apoptosis via AMPK-FOXO3a Signal Pathway","volume":"8","author":"Fan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Radak, Z., Suzuki, K., Posa, A., Petrovszky, Z., Koltai, E., and Boldogh, I. (2020). The Systemic Role of SIRT1 in Exercise Mediated Adaptation. Redox Biol., 35.","DOI":"10.1016\/j.redox.2020.101467"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1139\/h11-070","article-title":"Deacetylation of PGC-1\u03b1 by SIRT1: Importance for Skeletal Muscle Function and Exercise-Induced Mitochondrial Biogenesis","volume":"36","author":"Gurd","year":"2011","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s13105-017-0576-y","article-title":"Multi-Regulatory Network of ROS: The Interconnection of ROS, PGC-1 Alpha, and AMPK-SIRT1 during Exercise","volume":"73","author":"Thirupathi","year":"2017","journal-title":"J. Physiol. Biochem."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Brown, E.L., Foletta, V.C., Wright, C.R., Sepulveda, P.V., Konstantopoulos, N., Sanigorski, A., Della Gatta, P., Cameron-Smith, D., Kralli, A., and Russell, A.P. (2018). PGC-1\u03b1 and PGC-1\u03b2 Increase Protein Synthesis via ERR\u03b1 in C2C12 Myotubes. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01336"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1021\/acschembio.2c00720","article-title":"Synthetic ERR\u03b1\/\u03b2\/\u03b3 Agonist Induces an ERR\u03b1-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity","volume":"18","author":"Billon","year":"2023","journal-title":"ACS Chem. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Bonanni, R., Falvino, A., Matticari, A., Rinaldi, A.M., D\u2019Arcangelo, G., Cifelli, P., Iundusi, R., Gasbarra, E., Tancredi, V., and Cariati, I. (2025). Targeting ERRs to Counteract Age-Related Muscle Atrophy Associated with Physical Inactivity: A Pilot Study. Front. Physiol., 16.","DOI":"10.3389\/fphys.2025.1616693"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"260","DOI":"10.7150\/ijms.14586","article-title":"Effect of Exercise Training on Skeletal Muscle SIRT1 and PGC-1\u03b1 Expression Levels in Rats of Different Age","volume":"13","author":"Huang","year":"2016","journal-title":"Int. J. Med. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","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":"ref_85","doi-asserted-by":"crossref","unstructured":"Cariati, I., Bonanni, R., Romagnoli, C., Caprioli, L., D\u2019Arcangelo, G., Tancredi, V., and Annino, G. (2025). Bone Adaptations to a Whole Body Vibration Protocol in Murine Models of Different Ages: A Preliminary Study on Structural Changes and Biomarker Evaluation. J. Funct. Morphol. Kinesiol., 10.","DOI":"10.3390\/jfmk10010026"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Cariati, I., Bonanni, R., Rinaldi, A.M., Marini, M., Iundusi, R., Gasbarra, E., Tancredi, V., and Tarantino, U. (2023). Recombinant Irisin Prevents Cell Death and Mineralization Defects Induced by Random Positioning Machine Exposure in Primary Cultures of Human Osteoblasts: A Promising Strategy for the Osteoporosis Treatment. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1107933"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"14608","DOI":"10.1073\/pnas.1111308108","article-title":"Sirtuin-3 (Sirt3) Regulates Skeletal Muscle Metabolism and Insulin Signaling via Altered Mitochondrial Oxidation and Reactive Oxygen Species Production","volume":"108","author":"Jing","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhou, L., Pinho, R., Gu, Y., and Radak, Z. (2022). The Role of SIRT3 in Exercise and Aging. Cells, 11.","DOI":"10.3390\/cells11162596"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"eaaw7215","DOI":"10.1126\/sciadv.aaw7215","article-title":"Endoplasmic Reticulum Mediates Mitochondrial Transfer within the Osteocyte Dendritic Network","volume":"5","author":"Gao","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/cdd.2017.144","article-title":"SIRT3\/SOD2 Maintains Osteoblast Differentiation and Bone Formation by Regulating Mitochondrial Stress","volume":"25","author":"Gao","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1093\/gerona\/glu221","article-title":"Differential Effect of Endurance Training on Mitochondrial Protein Damage, Degradation, and Acetylation in the Context of Aging","volume":"70","author":"Johnson","year":"2015","journal-title":"J. Gerontol. A. Biol. Sci. Med. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41392-022-01233-2","article-title":"Molecular Mechanisms of Exercise Contributing to Tissue Regeneration","volume":"7","author":"Chen","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/j.cell.2018.10.025","article-title":"Irisin Mediates Effects on Bone and Fat via AV Integrin Receptors","volume":"175","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/j.celrep.2018.01.041","article-title":"\u03b2-Aminoisobutyric Acid, l-BAIBA, Is a Muscle-Derived Osteocyte Survival Factor","volume":"22","author":"Kitase","year":"2018","journal-title":"Cell Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6448","DOI":"10.7150\/thno.43577","article-title":"Exercise Protects Proliferative Muscle Satellite Cells against Exhaustion via the Igfbp7-Akt-MTOR Axis","volume":"10","author":"Chen","year":"2020","journal-title":"Theranostics"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"43928","DOI":"10.1074\/jbc.R112.406942","article-title":"Mammalian Target of Rapamycin (MTOR) Signaling Network in Skeletal Myogenesis","volume":"287","author":"Ge","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/s43587-023-00416-y","article-title":"Targeting the Biology of Aging with MTOR Inhibitors","volume":"3","author":"Mannick","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"585","DOI":"10.4196\/kjpp.2021.25.6.585","article-title":"Effects of Exercise on AKT\/PGC1-\u03b1\/FOXO3a Pathway and Muscle Atrophy in Cisplatin-Administered Rat Skeletal Muscle","volume":"25","author":"Bae","year":"2021","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zeng, Z., Liang, J., Wu, L., Zhang, H., Lv, J., and Chen, N. (2020). Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt\/MTOR and Akt\/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.583478"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.freeradbiomed.2021.11.030","article-title":"Nrf2 Contributes to the Benefits of Exercise Interventions on Age-Related Skeletal Muscle Disorder via Regulating Drp1 Stability and Mitochondrial Fission","volume":"178","author":"Yan","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.exger.2019.01.022","article-title":"Nrf2 Deficiency Exacerbates Frailty and Sarcopenia by Impairing Skeletal Muscle Mitochondrial Biogenesis and Dynamics in an Age-Dependent Manner","volume":"119","author":"Huang","year":"2019","journal-title":"Exp. Gerontol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1093\/gerona\/glx089","article-title":"Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women","volume":"72","author":"Alway","year":"2017","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"111111","DOI":"10.1016\/j.exger.2020.111111","article-title":"Resveratrol and Exercise Combined to Treat Functional Limitations in Late Life: A Pilot Randomized Controlled Trial","volume":"143","author":"Harper","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1002\/jbmr.4115","article-title":"Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial","volume":"35","author":"Wong","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41387-018-0059-4","article-title":"Effects of Resveratrol on Bone Health in Type 2 Diabetic Patients. A Double-Blind Randomized-Controlled Trial","volume":"8","author":"Bo","year":"2018","journal-title":"Nutr. Diabetes"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.2147\/CIA.S172758","article-title":"Efficacy and Safety of Co-Administration of Resveratrol with Meloxicam in Patients with Knee Osteoarthritis: A Pilot Interventional Study","volume":"13","author":"Hussain","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Vesely, O., Baldovska, S., and Kolesarova, A. (2021). Enhancing Bioavailability of Nutraceutically Used Resveratrol and Other Stilbenoids. Nutrients, 13.","DOI":"10.3390\/nu13093095"},{"key":"ref_108","first-page":"908","article-title":"Influence of Rapamycin on Safety and Healthspan Metrics after One Year: PEARL Trial Results","volume":"17","author":"Moel","year":"2025","journal-title":"Aging"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exger.2017.12.026","article-title":"A Randomized Control Trial to Establish the Feasibility and Safety of Rapamycin Treatment in an Older Human Cohort: Immunological, Physical Performance, and Cognitive Effects","volume":"105","author":"Kraig","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1007\/s11357-023-00935-x","article-title":"Blazing a Trail for the Clinical Use of Rapamycin as a GeroprotecTOR","volume":"45","author":"Konopka","year":"2023","journal-title":"GeroScience"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"268ra179","DOI":"10.1126\/scitranslmed.3009892","article-title":"MTOR Inhibition Improves Immune Function in the Elderly","volume":"6","author":"Mannick","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Harinath, G., Lee, V., Nyquist, A., Moel, M., Wouters, M., Hagemeier, J., Verkennes, B., Tacubao, C., Nasher, S., and Kauppi, K. (2025). The Bioavailability and Blood Levels of Low-Dose Rapamycin for Longevity in Real-World Cohorts of Normative Aging Individuals. GeroScience, 1\u201314.","DOI":"10.1007\/s11357-025-01532-w"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1038\/s41591-024-03096-2","article-title":"Effects of Intermittent Senolytic Therapy on Bone Metabolism in Postmenopausal Women: A Phase 2 Randomized Controlled Trial","volume":"30","author":"Farr","year":"2024","journal-title":"Nat. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s00774-025-01592-0","article-title":"Quercetins Efficacy on Bone and Inflammatory Markers, Body Composition, and Physical Function in Postmenopausal Women","volume":"43","author":"Bailly","year":"2025","journal-title":"J. Bone Miner. Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00394-025-03634-9","article-title":"Quercetin Ingestion Alters Motor Unit Behavior and Enhances Improvement in Muscle Strength Following Resistance Training in Older Adults: A Randomized, Double-Blind, Controlled Trial","volume":"64","author":"Nishikawa","year":"2025","journal-title":"Eur. J. Nutr."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Georgiou, N., Kakava, M.G., Routsi, E.A., Petsas, E., Stavridis, N., Freris, C., Zoupanou, N., Moschovou, K., Kiriakidi, S., and Mavromoustakos, T. (2023). Quercetin: A Potential Polydynamic Drug. Molecules, 28.","DOI":"10.3390\/molecules28248141"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1089\/jmf.2020.4778","article-title":"The Efficacy of the Novel Bioavailable Curcumin (Cureit) in the Management of Sarcopenia in Healthy Elderly Subjects: A Randomized, Placebo-Controlled, Double-Blind Clinical Study","volume":"24","author":"Varma","year":"2021","journal-title":"J. Med. Food"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/fsn3.2674","article-title":"Efficacy of Nanomicelle Curcumin, Nigella Sativa Oil, and Their Combination on Bone Turnover Markers and Their Safety in Postmenopausal Women with Primary Osteoporosis and Osteopenia: A Triple-Blind Randomized Controlled Trial","volume":"10","author":"Kheiridoost","year":"2022","journal-title":"Food Sci. Nutr."},{"key":"ref_119","first-page":"282","article-title":"Novel Nanomicelle Formulation to Enhance Bioavailability and Stability of Curcuminoids","volume":"22","author":"Hatamipour","year":"2019","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Vallibhakara, S.A.-O., Nakpalat, K., Sophonsritsuk, A., Tantitham, C., and Vallibhakara, O. (2021). Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind, Randomized, Placebo-Controlled Trial. Nutrients, 13.","DOI":"10.3390\/nu13124226"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.clnu.2017.12.020","article-title":"A High Whey Protein, Vitamin D and E Supplement Preserves Muscle Mass, Strength, and Quality of Life in Sarcopenic Older Adults: A Double-Blind Randomized Controlled Trial","volume":"38","author":"Bo","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/nure.12026","article-title":"Bioavailability of Vitamin E in Humans: An Update","volume":"71","author":"Borel","year":"2013","journal-title":"Nutr. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Squadrito, F., Imbalzano, E., Rottura, M., Arcoraci, V., Pallio, G., Catalano, A., Atteritano, M., Irrera, N., Mannino, F., and Squadrito, G. (2023). Effects of Genistein Aglycone in Glucocorticoid Induced Osteoporosis: A Randomized Clinical Trial in Comparison with Alendronate. Biomed. Pharmacother., 163.","DOI":"10.1016\/j.biopha.2023.114821"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4787","DOI":"10.1210\/jc.2008-1087","article-title":"Breast Safety and Efficacy of Genistein Aglycone for Postmenopausal Bone Loss: A Follow-up Study","volume":"93","author":"Marini","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00394-012-0304-x","article-title":"Effect of a Combination of Genistein, Polyunsaturated Fatty Acids and Vitamins D3 and K1 on Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled, Double-Blind Pilot Study","volume":"52","author":"Lappe","year":"2013","journal-title":"Eur. J. Nutr."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"839","DOI":"10.7326\/0003-4819-146-12-200706190-00005","article-title":"Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women: A Randomized Trial","volume":"146","author":"Marini","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Arcoraci, V., Atteritano, M., Squadrito, F., D\u2019Anna, R., Marini, H., Santoro, D., Minutoli, L., Messina, S., Altavilla, D., and Bitto, A. (2017). Antiosteoporotic Activity of Genistein Aglycone in Postmenopausal Women: Evidence from a Post-Hoc Analysis of a Multicenter Randomized Controlled Trial. Nutrients, 9.","DOI":"10.3390\/nu9020179"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.2174\/187152012803833107","article-title":"Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on Its ADME","volume":"12","author":"Yang","year":"2012","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Anupongsanugool, E., Teekachunhatean, S., Rojanasthien, N., Pongsatha, S., and Sangdee, C. (2005). Pharmacokinetics of Isoflavones, Daidzein and Genistein, after Ingestion of Soy Beverage Compared with Soy Extract Capsules in Postmenopausal Thai Women. BMC Clin. Pharmacol., 5.","DOI":"10.1186\/1472-6904-5-2"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1017\/jns.2022.72","article-title":"Enhanced Bioavailability and Pharmacokinetics of a Novel Hybrid-Hydrogel Formulation of Fisetin Orally Administered in Healthy Individuals: A Randomised Double-Blinded Comparative Crossover Study","volume":"11","author":"Krishnakumar","year":"2022","journal-title":"J. Nutr. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Szymczak, J., and Cielecka-Piontek, J. (2023). Fisetin-In Search of Better Bioavailability-From Macro to Nano Modifications: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814158"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1123\/japa.2017-0389","article-title":"Improvement in Skeletal Muscle Strength and Plasma Levels of Follistatin and Myostatin Induced by an 8-Week Resistance Training and Epicatechin Supplementation in Sarcopenic Older Adults","volume":"27","author":"Mafi","year":"2019","journal-title":"J. Aging Phys. Act."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mam.2017.11.002","article-title":"Absorption, Metabolism, Distribution and Excretion of (-)-Epicatechin: A Review of Recent Findings","volume":"61","author":"Borges","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"105587","DOI":"10.1016\/j.archger.2024.105587","article-title":"Metformin Improves Skeletal Muscle and Physical Capacity by Stabilizing Neuromuscular Junction in Older Adults","volume":"127","author":"Qaisar","year":"2024","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00774-014-0581-y","article-title":"Evaluation of the Anti-Osteoporotic Effects of Metformin and Sitagliptin in Postmenopausal Diabetic Women","volume":"33","author":"Hegazy","year":"2015","journal-title":"J. Bone Miner. Metab."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1002\/jcsm.13509","article-title":"Effects of Exercise or Metformin on Myokine Concentrations in Patients with Breast and Colorectal Cancer: A Phase II Multi-Centre Factorial Randomized Trial","volume":"15","author":"Brown","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"120113","DOI":"10.1016\/j.ijpharm.2020.120113","article-title":"Novel Self-Floating Tablet for Enhanced Oral Bioavailability of Metformin Based on Cellulose","volume":"592","author":"Na","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41584-020-00533-7","article-title":"Mechanisms and Therapeutic Implications of Cellular Senescence in Osteoarthritis","volume":"17","author":"Coryell","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and Aging-Related Diseases: From Molecular Mechanisms to Interventions and Treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10522-021-09910-5","article-title":"Aging and Age-Related Diseases: From Mechanisms to Therapeutic Strategies","volume":"22","author":"Li","year":"2021","journal-title":"Biogerontology"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.bbadis.2014.10.005","article-title":"The Molecular Targets of Resveratrol","volume":"1852","author":"Kulkarni","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3892\/ijmm.2023.5321","article-title":"Quercetin Alleviates Lipopolysaccharide-induced Acute Lung Injury by Inhibiting Ferroptosis via the Sirt1\/Nrf2\/Gpx4 Pathway","volume":"52","author":"Deng","year":"2023","journal-title":"Int. J. Mol. Med."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Wang, K. (2024). The Potential Therapeutic Role of Curcumin in Osteoporosis Treatment: Based on Multiple Signaling Pathways. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1446536"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Lu, R., Zheng, Z., Yin, Y., and Jiang, Z. (2020). Genistein Prevents Bone Loss in Type 2 Diabetic Rats Induced by Streptozotocin. Food Nutr. Res., 64.","DOI":"10.29219\/fnr.v64.3666"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"106504","DOI":"10.1016\/j.phrs.2022.106504","article-title":"The Effects of Fisetin on Bone and Cartilage: A Systematic Review","volume":"185","author":"Yamaura","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.bbrc.2022.09.074","article-title":"Metformin Mitigates Cholesterol Accumulation via the AMPK\/SIRT1 Pathway to Protect Osteoarthritis Chondrocytes","volume":"632","author":"Xing","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"765","DOI":"10.18632\/aging.204511","article-title":"Senolytic Effect of High Intensity Interval Exercise on Human Skeletal Muscle","volume":"15","author":"Jean","year":"2023","journal-title":"Aging"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"8599","DOI":"10.18632\/aging.205827","article-title":"Senolytic Effects of Exercise in Human Muscles Require Acute Inflammation","volume":"16","author":"Jean","year":"2024","journal-title":"Aging"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Elliehausen, C.J., Anderson, R.M., Diffee, G.M., Rhoads, T.W., Lamming, D.W., Hornberger, T.A., and Konopka, A.R. (2023). Geroprotector Drugs and Exercise: Friends or Foes on Healthy Longevity?. BMC Biol., 21.","DOI":"10.1186\/s12915-023-01779-9"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/s41467-020-14734-x","article-title":"Exercise Enhances Skeletal Muscle Regeneration by Promoting Senescence in Fibro-Adipogenic Progenitors","volume":"11","author":"Saito","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s10522-023-10024-3","article-title":"An AMP Kinase-Pathway Dependent Integrated Stress Response Regulates Ageing and Longevity","volume":"24","author":"Keizer","year":"2023","journal-title":"Biogerontology"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Juan, C.G., Matchett, K.B., and Davison, G.W. (2023). A Systematic Review and Meta-Analysis of the SIRT1 Response to Exercise. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-38843-x"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1016\/j.bbamcr.2014.08.010","article-title":"PGC-1\u03b1 and PGC-1\u03b2 Increase CrT Expression and Creatine Uptake in Myotubes via ERR\u03b1","volume":"1843","author":"Brown","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e2302360120","DOI":"10.1073\/pnas.2302360120","article-title":"Impaired Age-Associated Mitochondrial Translation Is Mitigated by Exercise and PGC-1\u03b1","volume":"120","author":"Leuchtmann","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"R490","DOI":"10.1152\/ajpregu.00261.2022","article-title":"Clock Genes Regulate Skeletal Muscle Energy Metabolism through NAMPT\/NAD(+)\/SIRT1 Following Heavy-Load Exercise","volume":"325","author":"Xia","year":"2023","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Zhou, X.-H., Luo, Y.-X., and Yao, X.-Q. (2025). Exercise-Driven Cellular Autophagy: A Bridge to Systematic Wellness. J. Adv. Res.","DOI":"10.1016\/j.jare.2024.12.036"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.smhs.2024.01.005","article-title":"Identification of Key Genes and Signaling Pathways Based on Transcriptomic Studies of Aerobic and Resistance Training Interventions in Sarcopenia in SAMP8 Mice","volume":"6","author":"Li","year":"2024","journal-title":"Sports Med. Health Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/s12276-022-00811-2","article-title":"Exercise-Induced FNDC5\/Irisin Protects Nucleus Pulposus Cells against Senescence and Apoptosis by Activating Autophagy","volume":"54","author":"Zhou","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1113\/JP275972","article-title":"Metabolic Stress-Dependent Regulation of the Mitochondrial Biogenic Molecular Response to High-Intensity Exercise in Human Skeletal Muscle","volume":"596","author":"Fiorenza","year":"2018","journal-title":"J. Physiol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Nieman, D.C., Kay, C.D., Rathore, A.S., Grace, M.H., Strauch, R.C., Stephan, E.H., Sakaguchi, C.A., and Lila, M.A. (2018). Increased Plasma Levels of Gut-Derived Phenolics Linked to Walking and Running Following Two Weeks of Flavonoid Supplementation. Nutrients, 10.","DOI":"10.3390\/nu10111718"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7573\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:23:46Z","timestamp":1760034226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":160,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157573"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157573","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,5]]}}}