{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:50:39Z","timestamp":1790254239456,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Veteran Affairs RR&amp;D","award":["RX001066"],"award-info":[{"award-number":["RX001066"]}]},{"name":"NIH - NIA","award":["5K07AG06026602"],"award-info":[{"award-number":["5K07AG06026602"]}]},{"name":"Indian Trail Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Low 25-OH serum vitamin D (VitD) is pervasive in older adults and linked to functional decline and progression of frailty. We have previously shown that chronic VitD insufficiency in \u201cmiddle-aged\u201d mice results in impaired anaerobic exercise capacity, decreased lean mass, and increased adiposity. Here, we examine if VitD insufficiency results in similar deficits and greater frailty progression in old-aged (24 to 28 months of age) mice. Similar to what we report in younger mice, older mice exhibit a rapid and sustained response in serum 25-OH VitD levels to differential supplementation, including insufficient (125 IU\/kg chow), sufficient (1000 IU\/kg chow), and hypersufficient (8000 IU\/kg chow) groups. During the 4-month time course, mice were assessed for body composition (DEXA), physical performance, and frailty using a Fried physical phenotype-based assessment tool. The 125 IU mice exhibited worse grip strength (p = 0.002) and inverted grip hang time (p = 0.003) at endpoint and the 8000 IU mice transiently displayed greater rotarod performance after 3 months (p = 0.012), yet other aspects including treadmill performance and gait speed were unaffected. However, 125 and 1000 IU mice exhibited greater frailty compared to baseline (p = 0.001 and p = 0.038, respectively), whereas 8000 IU mice did not (p = 0.341). These data indicate targeting higher serum 25-OH vitamin D levels may attenuate frailty progression during aging.<\/jats:p>","DOI":"10.3390\/nu12103005","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T09:41:01Z","timestamp":1601458861000},"page":"3005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Vitamin D Insufficiency Reduces Grip Strength, Grip Endurance and Increases Frailty in Aged C57Bl\/6J Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1989-6698","authenticated-orcid":false,"given":"Kenneth Ladd","family":"Seldeen","sequence":"first","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem Nagi","family":"Berman","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manhui","family":"Pang","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginger","family":"Lasky","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carleara","family":"Weiss","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian Alexander","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkumar","family":"Thiyagarajan","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonas","family":"Redae","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3699-0021","authenticated-orcid":false,"given":"Bruce Robert","family":"Troen","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1111\/j.1532-5415.2012.04054.x","article-title":"Prevalence of Frailty in Community-Dwelling Older Persons: A Systematic Review","volume":"60","author":"Collard","year":"2012","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.maturitas.2013.10.005","article-title":"Frailty in INstitutionalized older adults from ALbacete. The FINAL Study: Rationale, design, methodology, prevalence and attributes","volume":"77","author":"Abizanda","year":"2014","journal-title":"Maturitas"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jsbmb.2013.11.003","article-title":"Is vitamin D deficiency a major global public health problem?","volume":"144","author":"Palacios","year":"2014","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/953241","article-title":"Vitamin D: A Review on Its Effects on Muscle Strength, the Risk of Fall, and Frailty","volume":"2015","author":"Halfon","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_5","first-page":"313","article-title":"The problems of vitamin d insufficiency in older people","volume":"3","author":"Boucher","year":"2012","journal-title":"Aging Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.arr.2015.01.001","article-title":"Oxidation events and skin aging","volume":"21","author":"Kammeyer","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00508-016-1087-5","article-title":"Frailty and sarcopenia in elderly","volume":"128","author":"Morley","year":"2016","journal-title":"Wien Klin Wochenschr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Remelli, F., Vitali, A., Zurlo, A., and Volpato, S. (2019). Vitamin D Deficiency and Sarcopenia in Older Persons. Nutrients, 11.","DOI":"10.3390\/nu11122861"},{"key":"ref_9","first-page":"1338","article-title":"Chronic vitamin D insufficiency impairs physical performance in C57BL\/6J mice","volume":"10","author":"Seldeen","year":"2018","journal-title":"Aging (Albany N. Y.)"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbr.2004.07.008","article-title":"Behavioural characterization of vitamin D receptor knockout mice","volume":"157","author":"Burne","year":"2005","journal-title":"Behav. Brain Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jsbmb.2009.03.007","article-title":"Premature aging in vitamin D receptor mutant mice","volume":"115","author":"Keisala","year":"2009","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jsbmb.2009.01.020","article-title":"Vestibular dysfunction in vitamin D receptor mutant mice","volume":"114","author":"Minasyan","year":"2009","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6139","DOI":"10.1210\/jc.2019-00573","article-title":"Association Between Vitamin D, Frailty, and Progression of Frailty in Community-Dwelling Older Women","volume":"104","author":"Buchebner","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ju, S.Y., Lee, J.Y., and Kim, D.H. (2018). Low 25-hydroxyvitamin D levels and the risk of frailty syndrome: A systematic review and dose-response meta-analysis. BMC Geriatr., 18.","DOI":"10.1186\/s12877-018-0904-2"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mad.2019.01.008","article-title":"Rodent models of frailty and their application in preclinical research","volume":"179","author":"Banga","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s11914-015-0283-y","article-title":"Mouse Models of Frailty: An Emerging Field","volume":"13","author":"Seldeen","year":"2015","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in older adults: Evidence for a phenotype","volume":"56","author":"Fried","year":"2001","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/gerona\/glx120","article-title":"High Intensity Interval Training Improves Physical Performance and Frailty in Aged Mice","volume":"73","author":"Seldeen","year":"2018","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.mad.2019.04.001","article-title":"High intensity interval training improves physical performance in aged female mice: A comparison of mouse frailty assessment tools","volume":"180","author":"Seldeen","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s11357-013-9589-9","article-title":"Battery of behavioral tests in mice that models age-associated changes in human motor function","volume":"36","author":"Justice","year":"2014","journal-title":"Age (Dordr.)"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Seldeen, K.L., Redae, Y.Z., Thiyagarajan, R., Berman, R.N., Leiker, M.M., and Troen, B.R. (2019). Short Session High Intensity Interval Training and Treadmill Assessment in Aged Mice. J. Vis. Exp., e59138.","DOI":"10.3791\/59138"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/cphy.c140071","article-title":"PTH and Vitamin D","volume":"6","author":"Khundmiri","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ekwaru, J.P., Zwicker, J.D., Holick, M.F., Giovannucci, E., and Veugelers, P.J. (2014). The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111265"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4103\/ijpvm.IJPVM_329_15","article-title":"Effect of Vitamin D Supplementation on Weight Loss, Glycemic Indices, and Lipid Profile in Obese and Overweight Women: A Clinical Trial Study","volume":"9","author":"Khosravi","year":"2018","journal-title":"Int. J. Prev. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jsbmb.2017.03.018","article-title":"Vitamin D and muscle function","volume":"173","year":"2017","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12986-017-0174-6","article-title":"A mouse model of vitamin D insufficiency: Is there a relationship between 25(OH) vitamin D levels and obesity?","volume":"14","author":"Seldeen","year":"2017","journal-title":"Nutr. Metab. (Lond.)"},{"key":"ref_27","first-page":"483","article-title":"Time Course of Vitamin D Depletion and Repletion in Reproductive-age Female C57BL\/6 Mice","volume":"67","author":"Belenchia","year":"2017","journal-title":"Comp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.bonr.2017.02.001","article-title":"High dose dietary vitamin D3 increases bone mass and strength in mice","volume":"6","author":"Williamson","year":"2017","journal-title":"Bone Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/21551197.2013.867825","article-title":"Vitamin D status is associated with grip strength in centenarians","volume":"33","author":"Haslam","year":"2014","journal-title":"J. Nutr. Gerontol. Geriatr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1053\/j.jrn.2015.08.007","article-title":"The \u201cDose-Effect\u201d Relationship Between 25-Hydroxyvitamin D and Muscle Strength in Hemodialysis Patients Favors a Normal Threshold of 30 ng\/mL for Plasma 25-Hydroxyvitamin D","volume":"26","author":"Bataille","year":"2016","journal-title":"J. Ren. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/gerona\/glq235","article-title":"Change in 25-hydroxyvitamin D and physical performance in older adults","volume":"66","author":"Houston","year":"2011","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Toffanello, E.D., Perissinotto, E., Sergi, G., Zambon, S., Musacchio, E., Maggi, S., Coin, A., Sartori, L., Corti, M.C., and Baggio, G. (2012). Vitamin D and physical performance in elderly subjects: The Pro.V.A study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034950"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9773","DOI":"10.1007\/s11357-015-9773-1","article-title":"C57BL\/6 life span study: Age-related declines in muscle power production and contractile velocity","volume":"37","author":"Graber","year":"2015","journal-title":"Age (Dordr.)"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3897\/folmed.61.e39346","article-title":"Associations between Handgrip Strength and Vitamin 25(OH)D Levels in Geriatric Patients","volume":"61","author":"Aksoy","year":"2019","journal-title":"Folia Med. (Plovdiv.)"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"85","DOI":"10.23736\/S0022-4707.19.09607-5","article-title":"Physical performance is not improved with vitamin D repletion: A randomized trial","volume":"60","author":"Scholten","year":"2020","journal-title":"J. Sports Med. Phys. Fitness"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1159\/000504873","article-title":"Effect of Vitamin D Supplementation on Body Composition and Physical Fitness in Healthy Adults: A Double-Blind, Randomized Controlled Trial","volume":"75","author":"Sun","year":"2019","journal-title":"Ann. Nutr. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/jbmr.2317","article-title":"Vitamin D receptor signaling enhances locomotive ability in mice","volume":"30","author":"Sakai","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.ecl.2017.07.004","article-title":"Effect of Vitamin D on Falls and Physical Performance","volume":"46","author":"Dhaliwal","year":"2017","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00132-017-3446-y","article-title":"The effect of vitamin D and calcium supplementation on falls in older adults: A systematic review and meta-analysis","volume":"46","author":"Wu","year":"2017","journal-title":"Orthopade"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/S0167-4943(10)70006-6","article-title":"Vitamin D insufficiency and frailty syndrome in older adults living in a Northern Taiwan community","volume":"50","author":"Chang","year":"2010","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/gerona\/gln007","article-title":"Association of low vitamin D levels with the frailty syndrome in men and women","volume":"64","author":"Shardell","year":"2009","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/s12603-014-0546-9","article-title":"Association of low 25-hydroxyvitamin D levels with the frailty syndrome in an aged population: Results from the KORA-age Augsburg study","volume":"19","author":"Pabst","year":"2015","journal-title":"J. Nutr. Health Aging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10654-014-9894-3","article-title":"Is vitamin D deficiency a cause of increased morbidity and mortality at older age or simply an indicator of poor health?","volume":"29","author":"Schottker","year":"2014","journal-title":"Eur. J. Epidemiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5266","DOI":"10.1210\/jc.2010-2317","article-title":"Study of Osteoporotic Fractures Research G: Circulating 25-hydroxyvitamin D levels and frailty status in older women","volume":"95","author":"Ensrud","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1159\/000501333","article-title":"Frailty Assessment in Animal Models","volume":"65","author":"Banga","year":"2019","journal-title":"Gerontology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Burt, L.A., Billington, E.O., Rose, M.S., Kremer, R., Hanley, D.A., and Boyd, S.K. (2020). Adverse Effects of High-Dose Vitamin D Supplementation on Volumetric Bone Density Are Greater in Females than Males. J. Bone Miner. Res.","DOI":"10.1002\/jbmr.4152"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/10\/3005\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:15:12Z","timestamp":1760177712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/10\/3005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,30]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["nu12103005"],"URL":"https:\/\/doi.org\/10.3390\/nu12103005","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,30]]}}}