{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:46:03Z","timestamp":1791996363733,"version":"4.4.0"},"reference-count":71,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gerontology"],"abstract":"<jats:p>Background: Mitochondrial dysfunction serves as a fundamental driver of the aging process, precipitating progressive functional decline through complex molecular cascades. Summary: This review elucidates the core mechanisms underpinning this dysfunction, including reactive oxygen species-induced redox imbalance, mitochondrial DNA damage accumulation, impaired mitophagy, and metabolic reprogramming. Crucially, we examine how mitochondria act as signaling hubs for inter-organ crosstalk. Through the secretion of mitokines (e.g., FGF21 and GDF15) and the release of damage-associated molecular patterns, dysfunctional mitochondria trigger chronic inflammation via the cyclic GMP-AMP synthase-stimulator of interferon genes and NLRP3 inflammasome (NLRP3) pathways, actively driving systemic aging within the skeletal muscle-brain and adipose\/liver-cardiovascular axes. Additionally, this paper synthesizes current therapeutic interventions, ranging from lifestyle modifications and nicotinamide adenine dinucleotide (NAD+) precursors to frontier technologies like mitochondrial transplantation and gene editing. Key Messages: While promising in animal models, clinical translation of these interventions is currently hindered by limited long-term safety data and evidence gaps. Therefore, mitochondria-targeted studies incorporating integrated multi-organ phenotyping are urgently required to establish robust strategies for extending human healthspan.<\/jats:p>","DOI":"10.1159\/000553430","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:00:52Z","timestamp":1786982452000},"page":"1-14","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Dysfunction as a Central Hub of Aging: From Molecular Cascades to Inter-Organ Communication 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