{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:16:59Z","timestamp":1788225419758,"version":"build-2803163510"},"reference-count":142,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Lithium remains the gold-standard maintenance treatment for bipolar disorder (BD) and is distinguished by its unique anti-suicidal and neuroprotective properties. Beyond its established psychiatric efficacy, growing evidence suggests that lithium may modulate fundamental mechanisms of biological aging. In parallel, cellular senescence has emerged as a central process linking oxidative stress, chronic inflammation, mitochondrial dysfunction, and impaired cellular resilience with neurodegeneration and psychiatric disease. Notably, BD is increasingly associated with features of accelerated aging, including telomere shortening, increased inflammatory burden, and structural brain changes consistent with premature brain aging. In this review, we discuss current evidence supporting lithium as a potential senostatic agent in the central nervous system. Experimental studies indicate that lithium attenuates several hallmarks of cellular senescence and promotes cellular resilience under conditions of oxidative, inflammatory, and genotoxic stress. These effects appear to involve coordinated modulation of neuroinflammatory signaling, mitochondrial function, oxidative stress responses, genomic stability, and neurotrophic pathways. Clinical findings further suggest that chronic lithium treatment may be associated with preserved telomere length and attenuated biological brain aging in BD. Collectively, the available data support a model in which lithium acts not only as a mood stabilizer but also as a broader regulator of aging-associated processes relevant to neuropsychiatric and neurodegenerative disorders. Although the senomodulatory effects of lithium appear context- and cell-type-dependent, its established clinical use and pleiotropic biological actions make it a promising candidate for translational senotherapeutic research.<\/jats:p>","DOI":"10.3390\/ph19091378","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:05:26Z","timestamp":1788224726000},"page":"1378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lithium as a Potential Senostatic Agent in Central Nervous System Aging and Bipolar Disorder"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0577-0381","authenticated-orcid":false,"given":"Janusz K.","family":"Rybakowski","sequence":"first","affiliation":[{"name":"Department of Adult Psychiatry, Pozna\u0144 University of Medical Sciences, Szpitalna 27\/33, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6804-8347","authenticated-orcid":false,"given":"Cezary","family":"Mydlak","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Ageing and Civilization Diseases, Pozna\u0144 University of Medical Sciences, \u015awi\u0119cickiego 4 Str., 60-781 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadzieja","family":"Klimek","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Prince Mieszko I Poznan Medical University of Applied Sciences, Bulgarska 55 Str., 60-320 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6066-5747","authenticated-orcid":false,"given":"Krzysztof","family":"Ksi\u0105\u017cek","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Prince Mieszko I Poznan Medical University of Applied Sciences, Bulgarska 55 Str., 60-320 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41581-022-00601-z","article-title":"Cellular senescence: The good, the bad and the unknown","volume":"18","author":"Huang","year":"2022","journal-title":"Nat. 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