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Senescent cells have been shown to increase in multiple organs during aging, including the skin. Here we hypothesized that senescent cells residing in the skin can spread senescence to distant organs, thereby accelerating systemic aging processes. To explore this hypothesis, we initially observed an increase in several markers of senescence in the skin of aging mice. Subsequently, we conducted experiments wherein senescent fibroblasts were transplanted into the dermis of young mice and assessed various age\u2010associated parameters. Our findings reveal that the presence of senescent cells in the dermal layer of young mice leads to increased senescence in both proximal and distal host tissues, alongside increased frailty, and impaired musculoskeletal function. Additionally, there was a significant decline in cognitive function, concomitant with increased expression of senescence\u2010associated markers within the hippocampus brain area. These results support the concept that the accumulation of senescent cells in the skin can exert remote effects on other organs including the brain, potentially explaining links between skin and brain disorders and diseases and, contributing to physical and cognitive decline associated with aging.<\/jats:p>","DOI":"10.1111\/acel.14340","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T16:39:13Z","timestamp":1728319153000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Senescent cell transplantation into the skin induces age\u2010related peripheral dysfunction and cognitive decline"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-7021","authenticated-orcid":false,"given":"Ana Catarina","family":"Franco","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"},{"name":"CNC\u2013Center for Neuroscience and Cell Biology (CNC\u2010UC) University of Coimbra  Coimbra Portugal"},{"name":"Centre for Innovation in Biomedicine and Biotechnology (CIBB) University of Coimbra  Coimbra Portugal"},{"name":"Faculty of Pharmacy University of Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Victorelli","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony B.","family":"Lagnado","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranya P.","family":"Wyles","sequence":"additional","affiliation":[{"name":"Department of Dermatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Rowsey","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Pirius","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Hwa","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela G.","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Robert and Arlene Kogod Center on Aging Mayo Clinic  Rochester Minnesota USA"},{"name":"CNC\u2013Center for Neuroscience and Cell Biology (CNC\u2010UC) University of Coimbra  Coimbra Portugal"},{"name":"Centre for Innovation in Biomedicine and Biotechnology (CIBB) University of Coimbra  Coimbra Portugal"},{"name":"Faculty of Pharmacy University of Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0497-2002","authenticated-orcid":false,"given":"Selim","family":"Chaib","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering Mayo Clinic  Rochester Minnesota USA"},{"name":"Center for Advanced Gerotherapeutics, Division of Endocrinology Diabetes &amp; 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