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Aging is a complex biological process characterized by a gradual decline in cellular and physiological function, increasing vulnerability to chronic diseases and mortality. It involves a set of interconnected mechanisms known as the hallmarks of aging, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, and dysregulated nutrient sensing. These processes act at molecular, cellular, and systemic levels, contributing to age-related disorders such as neurodegeneration, cardiovascular disease, and metabolic syndromes. Emerging therapeutic strategies aim to delay or reverse aging by targeting specific hallmarks. These include senolytics to eliminate senescent cells, NAD boosters and mitophagy inducers to improve mitochondrial health, epigenetic reprogramming, and caloric restriction mimetics such as metformin and rapamycin to modulate nutrient-sensing pathways. Advances in regenerative medicine, gene editing, and organ cross-talk modulation are also contributing to the development of personalized, multi-targeted anti-aging therapies. Integration of omics technologies and biomarker research is expected to enhance our ability to monitor biological aging and optimize interventions for healthy longevity. This review highlights the current understanding of the hallmarks of aging and explores potential treatment strategies in light of our recent findings.
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http://dx.doi.org/10.3389/fcvm.2025.1631578 | DOI Listing |
Cell Rep
September 2025
Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address:
Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production.
View Article and Find Full Text PDFJ Cosmet Dermatol
September 2025
Cosmetic Laser Dermatology, San Diego, California, USA.
Background: With the rise of regenerative medicine and geroscience, translational research has shifted focus from lifespan to healthspan-years lived in good health. Applied to aesthetic medicine, the authors introduce the concept of "skinspan," to both describe the period during which skin maintains a youthful, healthy appearance, and additionally to serve as a tool for the cosmetic consult.
Aims: The aim of this comprehensive review is to illuminate "skinspan" as a framework for guiding long-term skin health.
Ageing Res Rev
September 2025
Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy; Department of Medicine and Surgery, LUM University, Casamassima, Italy. Electronic address:
Nuclear insertions of mitochondrial DNA (mtDNA) segments (NUMTs) represent an evolutionarily conserved phenomenon originating from the ancient endosymbiotic relationship between mitochondria and host cells. These insertions predominantly localize near intergenic or regulatory regions and are often enriched in tissues with high metabolic activity. Once regarded as inert pseudogenes or genomic artifacts, NUMTs are now recognized as dynamic elements capable of modulating nuclear architecture and cellular function.
View Article and Find Full Text PDFInn Med (Heidelb)
September 2025
Comprehensive Cancer Center, Universitätsklinik Würzburg, Würzburg, Deutschland.
Frailty is a common geriatric syndrome in older patients with cancer. It affects prognosis and treatment tolerance in various ways. Frailty and cancer share several common risk factors, which are reflected in the hallmarks of aging.
View Article and Find Full Text PDFInt J Mol Med
November 2025
Department of Hepatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China.
Cellular senescence, a hallmark of aging, is characterized by irreversible, permanent cell cycle arrest accompanied by halted proliferation triggered by endogenous or exogenous stimuli. The accumulation of senescent cells in tissues or organs elicits detrimental effects on adjacent normal cells through their pathogenic senescence‑associated secretory phenotype (SASP), driving secondary senescence, disrupting tissue homeostasis and ultimately exacerbating age‑related pathologies such as types of cancer and neurodegenerative disorders. Hepatic disorders constitute a leading cause of global mortality, imposing considerable healthcare burdens.
View Article and Find Full Text PDF