{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:58:37Z","timestamp":1785560317748,"version":"3.56.0"},"reference-count":22,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2019R1A2C1086882"],"award-info":[{"award-number":["2019R1A2C1086882"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2019R1A2C1086882"],"award-info":[{"award-number":["2019R1A2C1086882"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The Korean Health Technology R&D Project","award":["HI21C1713"],"award-info":[{"award-number":["HI21C1713"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Aging involves the accumulation of molecular alterations within cells and the extracellular matrix, resulting in cellular senescence and declining physiological functions. This study investigates the correlation between the biophysical environment and cellular aging, specifically examining how mechanical and biochemical cues affect cellular senescence and tissue degeneration. Cells were cultured on acrylamide hydrogels of different stiffnesses (4 and 19 kPa), and their mechanical properties were characterized by measuring Young\u2019s modulus via compression tests. Cell proliferation, morphology, gene and protein expression, and autophagy activity were assessed using multiple assays and imaging techniques. Cells cultured on stiff hydrogels exhibited elongated morphologies, whereas cells on soft hydrogels formed spherical clusters. Notably, longevity-associated genes were upregulated in cells cultured on softer substrates. Reversibility experiments demonstrated that the aging phenotype could be reversed by modulating mechanical culture conditions, with softer environments enhancing autophagic activity. In summary, hydrogel stiffness significantly impacts aging-related cellular behavior. These findings suggest biomechanical cues as a promising strategy to promote cellular rejuvenation and combat aging.<\/jats:p>","DOI":"10.3390\/cells15151380","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:15:00Z","timestamp":1785428100000},"page":"1380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reversible Mechano-Regulation of Cellular Senescence: Effects of Substrate Stiffness on Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0527-9103","authenticated-orcid":false,"given":"Jin Young","family":"An","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, College of Life Science, CHA University, Pocheon 11160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4336-122X","authenticated-orcid":false,"given":"Sung Won","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, College of Life Science, CHA University, Pocheon 11160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Dong","family":"Goo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, College of Life Science, CHA University, Pocheon 11160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, College of Life Science, CHA University, Pocheon 11160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Hong","family":"Kim","sequence":"additional","affiliation":[{"name":"Nano-Convergence Manufacturing Research Division, Korea Institute of Machinery and Materials (KIMM), Daejeon 34103, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5878-8054","authenticated-orcid":false,"given":"Su A","family":"Park","sequence":"additional","affiliation":[{"name":"Nano-Convergence Manufacturing Research Division, Korea Institute of Machinery and Materials (KIMM), Daejeon 34103, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid Ebrahimi","family":"Warkiani","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8735-444X","authenticated-orcid":false,"given":"Jae Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, College of Life Science, CHA University, Pocheon 11160, Republic of Korea"},{"name":"CHA Fertility Center Seoul Station, Seoul 04637, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1146\/annurev-bioeng-071114-040829","article-title":"The Mechanobiology of Aging","volume":"17","author":"Phillip","year":"2015","journal-title":"Annu. 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