{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:38:54Z","timestamp":1790537934747,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 AG62413"],"award-info":[{"award-number":["P01 AG62413"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG063543\u2010S1"],"award-info":[{"award-number":["R01 AG063543\u2010S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG72301"],"award-info":[{"award-number":["R01 AG72301"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33 AG61456"],"award-info":[{"award-number":["R33 AG61456"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37 AG13925"],"award-info":[{"award-number":["R37 AG13925"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AG056278"],"award-info":[{"award-number":["U19 AG056278"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016997","name":"NF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["agsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J American Geriatrics Society"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS\u2010CoV\u20102 infection. SARS\u2010CoV\u20102 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence\u2010associated secretory phenotype (SASP). The SASP can be amplified by infection\u2010related pathogen\u2010associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity\/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS\u2010CoV\u20102 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS\u2010CoV\u20102 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health\u2010funded, multicenter, placebo\u2010controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS\u2010CoV\u20102 rtPCR\u2010positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long\u2010term care settings in the SARS\u2010CoV\u20102 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.<\/jats:p>","DOI":"10.1111\/jgs.17416","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T12:53:42Z","timestamp":1628600022000},"page":"3023-3033","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Fisetin for\n                    <scp>COVID<\/scp>\n                    \u201019 in skilled nursing facilities: Senolytic trials in the\n                    <scp>COVID<\/scp>\n                    era"],"prefix":"10.1111","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4289-2740","authenticated-orcid":false,"given":"Brandon P.","family":"Verdoorn","sequence":"first","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"},{"name":"Division of Geriatrics and Gerontology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara K.","family":"Evans","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"},{"name":"Division of Geriatrics and Gerontology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa G. P.","family":"Langhi Prata","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Pignolo","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"},{"name":"Division of Geriatrics and Gerontology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Department of Health Sciences Research Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin O.","family":"Wissler\u2010Gerdes","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Kuchel","sequence":"additional","affiliation":[{"name":"University of Connecticut Center on Aging, UConn Health  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan B.","family":"Mannick","sequence":"additional","affiliation":[{"name":"Life Biosciences  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Kritchevsky","sequence":"additional","affiliation":[{"name":"Sticht Center for Healthy Aging and Alzheimer's Prevention  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundeep","family":"Khosla","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"},{"name":"Division of Endocrinology, Department of Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey A.","family":"Rizza","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy D.","family":"Walston","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Geriatric Medicine and Gerontology Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Musi","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis A.","family":"Lipsitz","sequence":"additional","affiliation":[{"name":"Hinda and Arthur Marcus Institute for Aging Research Hebrew SeniorLife  Boston Massachusetts USA"},{"name":"Division of Gerontology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas P.","family":"Kiel","sequence":"additional","affiliation":[{"name":"Hinda and Arthur Marcus Institute for Aging Research Hebrew SeniorLife  Boston Massachusetts USA"},{"name":"Division of Gerontology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Yung","sequence":"additional","affiliation":[{"name":"Geriatrics Center and Institute of Gerontology University of Michigan  Ann Arbor Michigan USA"},{"name":"VA Ann Arbor Geriatrics Research Education and Clinical Center  Ann Arbor Michigan USA"},{"name":"Department of Internal Medicine Division of Geriatric and Palliative Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan K.","family":"LeBrasseur","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Physical Medicine and Rehabilitation Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder J.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Puskarich","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Niedernhofer","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Sorenson","sequence":"additional","affiliation":[{"name":"Legal Contract Administration Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Tchkonia","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Kirkland","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"},{"name":"Division of Geriatrics and Gerontology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Provisional Death Counts for Coronavirus Disease 2019 (COVID\u201019). Centers for Disease Control and Prevention (CDC) National Center for Health Statistics 2020.https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/covid_weekly\/index.htm#AgeAndSex. Accessed January 29 2021."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001191"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.15957"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.16784"},{"key":"e_1_2_11_6_1","unstructured":"COVID\u201019 Nursing Home Data.Data.CMS.Gov.https:\/\/data.cms.gov\/stories\/s\/bkwz-xpvg. Accessed April 11 2021."},{"key":"e_1_2_11_7_1","unstructured":"State COVID\u201019 Data and Policy Actions.Kaiser Family Foundation.https:\/\/www.kff.org\/coronavirus-covid-19\/issue-brief\/state-covid-19-data-and-policy-actions\/#longtermcare. Accessed April 11 2021."},{"key":"e_1_2_11_8_1","unstructured":"The Advisory Committee on Immunization Practices' Updated Interim Recommendation for Allocation of COVID\u201019 Vaccine\u2014United States December 2020. Centers for Disease Control and Prevention.https:\/\/www.cdc.gov\/mmwr\/volumes\/69\/wr\/mm695152e2.htm?s_cid=mm695152e2_w. Accessed January 1 2021."},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01285-x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7017e2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.7326\/M20-3569"},{"key":"e_1_2_11_12_1","article-title":"Confidence and receptivity for COVID\u201019 vaccines: a rapid systematic review","volume":"9","author":"Lin C","year":"2020","journal-title":"Vaccines (Basel)"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7005e2"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.039"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18039-x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2020.03.008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.07.029"},{"key":"e_1_2_11_18_1","article-title":"Senolytics reduce coronavirus\u2010related mortality in old mice","author":"Camell MJY CD","year":"2021","journal-title":"Science"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glw086"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2012.11.014"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101202"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-015-1023-4"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.11.1233"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.17191"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2010.03032.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2006.01.024"},{"key":"e_1_2_11_27_1","unstructured":"COVID\u201019 Intensifies Nursing Home Workforce Challenges.Office of the Assistant Secretary for Planning and Evaluation.https:\/\/aspe.hhs.gov\/basic-report\/covid-19-intensifies-nursing-home-workforce-challenges. Accessed February 5 21."},{"key":"e_1_2_11_28_1","unstructured":"Nursing Home Visitation\u2010COVID\u201019.Centers for Medicare & Medicaid Services.https:\/\/www.cms.gov\/files\/document\/qso-20-39-nh.pdf. 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