{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:23:04Z","timestamp":1787574184698,"version":"build-2736575974"},"reference-count":395,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>\n                    The capacity for tissue repair and regeneration undergoes a profound and progressive decline across the human lifespan, representing a fundamental driver of aging and chronic disease. This review establishes a comprehensive ontogenetic framework by mapping the continuous biological transition from the flawless, scarless regenerative plasticity of embryonic development to the irreversible fibrotic scarring and organ failure characteristic of senescence. We synthesize the hierarchical collapse of reparative networks across multiple biological scales. Importantly, this ontogenetic decline should not be interpreted as a purely degenerative trajectory but rather as a dynamic systems-level reprogramming in which evolutionary trade-offs prioritize tumor suppression, immune surveillance, and reproductive fitness over long-term regenerative fidelity. Recognizing this adaptive reallocation of biological resources reframes aging not simply as failure but as a predictable recalibration of repair hierarchies. At the molecular and cellular levels, the accumulation of genomic instability, unresolvable DNA damage, and mitochondrial dysfunction gradually overwhelms intracellular quality-control mechanisms. Concurrently, epigenetic drift and chronic, low-grade systemic inflammation (\u201cinflammaging\u201d) dismantle the stem cell niche, driving adult stem cell exhaustion and shifting wound healing away from functional tissue replacement toward maladaptive fibrosis. Furthermore, we examine divergent, organ-specific repair trajectories. By contrasting the severe regenerative restrictions of the adult central nervous system and myocardium with the persistent, yet exhaustible, resilience of the liver, we elucidate the unique intrinsic and microenvironmental barriers that impede structural and functional recovery. Finally, we evaluate the clinical paradigm shift from passive management of age-related degeneration to active restoration of tissue integrity. By integrating systemic geroscience\u2014which addresses the global hallmarks of aging\u2014with targeted bioengineering and\n                    <jats:italic>in vivo<\/jats:italic>\n                    epigenetic modulation, contemporary regenerative medicine seeks to recreate permissive, youthful microenvironments. Ultimately, mastering these ontogenetic principles holds unprecedented potential to reactivate endogenous repair pathways, mitigate multi-organ collapse, and significantly extend human functional healthspan.\n                  <\/jats:p>","DOI":"10.3389\/fragi.2026.1888854","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:36:41Z","timestamp":1787571401000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Repair and regeneration across the lifespan: an ontogenetic perspective"],"prefix":"10.3389","volume":"7","author":[{"given":"Hugo A.","family":"Barrera-Salda\u00f1a","sequence":"first","affiliation":[{"name":"Innbiogem SC, Vitaxentrum","place":["Monterrey, M\u00e9xico"]},{"name":"Facultad de Ciencias Biol\u00f3gicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Ciudad Universitaria","place":["San Nicol\u00e1s de Los Garza, M\u00e9xico"]},{"name":"Facultad de Medicina, Universidad Aut\u00f3noma de Nuevo Le\u00f3n","place":["Monterrey, M\u00e9xico"]},{"name":"Direcci\u00f3n de Investigaci\u00f3n Cient\u00edfica, Laboratorios Columbia","place":["Coyoac\u00e1n, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E.","family":"Fern\u00e1ndez-Garza","sequence":"additional","affiliation":[{"name":"Innbiogem SC, Vitaxentrum","place":["Monterrey, M\u00e9xico"]},{"name":"Servicio de Neurolog\u00eda, Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n","place":["Monterrey, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Guillen-Silva","sequence":"additional","affiliation":[{"name":"Innbiogem SC, Vitaxentrum","place":["Monterrey, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar R.","family":"Fajardo-Ramirez","sequence":"additional","affiliation":[{"name":"Innbiogem SC, Vitaxentrum","place":["Monterrey, M\u00e9xico"]},{"name":"Laboratorio de Fisiolog\u00eda Molecular y Estructural, Facultad de Ciencias Biol\u00f3gicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Ciudad Universitaria","place":["San Nicol\u00e1s de Los Garza, M\u00e9xico"]},{"name":"Universidad Tecnol\u00f3gica de M\u00e9xico (UNITEC), Campus Monterrey","place":["San Nicol\u00e1s de Los Garza, Nuevo Le\u00f3n, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Francisco","family":"I\u00f1igo Pavlovich","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Diseases, Ti Orthopedica Institute","place":["Tijuana, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferm\u00edn Valenzuela","family":"G\u00f3mez-Gallardo","sequence":"additional","affiliation":[{"name":"Academia Nacional de Medicina de M\u00e9xico, Committee of Liaison and Dissemination of Knowledge","place":["Ciudad de M\u00e9xico, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Rodriguez-Fuentes","sequence":"additional","affiliation":[{"name":"Department of Biology, Skeletal Research Center, and Center for Modular Manufacturing of Structural Tissues, Case Western Reserve University","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia Y.","family":"Avila-Villalobos","sequence":"additional","affiliation":[{"name":"Innbiogem SC, Vitaxentrum","place":["Monterrey, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia A.","family":"Barrera-Barrera","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n","place":["Monterrey, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo A.","family":"Somoza","sequence":"additional","affiliation":[{"name":"Department of Biology, Skeletal Research Center, and Center for Modular Manufacturing of Structural Tissues, Case Western Reserve University","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/nature14289","article-title":"Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice","volume":"521","author":"Adam","year":"2015","journal-title":"Nature"},{"key":"B2","article-title":"Direct reversal repair in mammalian cells","volume-title":"En","author":"Ahmad","year":"2015"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5493\/wjem.v7.i1.1","article-title":"Effect of aging on stem cells","volume":"7","author":"Ahmed","year":"2017","journal-title":"World J. 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