Complosome as a key modulator of cellular senescence, aging and age-related diseases.

Pathogenic modulators of cellular senescence

Cellular senescence is characterized by irreversible cell-cycle arrest, with cells remaining viable and metabolically active. This state features a proinflammatory senescence-associated secretory phenotype (SASP) that can harm neighboring tissues. Accumulation of senescent cells accelerates age-related physiological decline and associated pathologies. Furthermore, cellular senescence is implicated in various physiological processes, including embryonic development, wound healing, tumor progression, and immune response regulation. The complexity of the aging process arises from its diverse underlying mechanisms, potential reversibility, and intrinsic heterogeneity. Experimental gerontology focuses on identifying pathogenic modulators that regulate the formation and accumulation of senescent cells, as well as investigating their impact on tissue function. Within the field of experimental gerontology, considerable attention is devoted to identifying pathogenic modulators that regulate the formation and accumulation of senescent cells, as well as to investigating their impact on tissue function. Of particular interest is the characterization of novel molecular mechanisms that govern cellular aging. Key pathogenic molecular pathways include the p53-dependent senescence pathway, the p16INK4a/pRb pathway, and non-canonical pathways like IFIH1-MAVS, which contribute to oxidative stress, DNA damage, activation of SASP, and other cellular dysfunction. This study critically examines how viral and bacterial agents induce cellular senescence, particularly in vitro , reviewing the regulatory mechanisms involved. It discusses genetic variants affecting infection susceptibility and categorizes senescence markers. Investigating the molecular mechanisms underlying cellular aging presents promising avenues for the development of targeted and effective therapeutic interventions. Such strategies may include the selective induction of senescence in cancer cells, suppression of senescence to mitigate age-related diseases, or the comprehensive modulation of aging processes to optimize clinical outcomes.

Understanding extracellular vesicles in antiaging.

BACKGROUND Aging is a multifactorial process marked by gradual cellular dysregulation, regulated by hallmarks, including genomic instability, mitochondrial dysregulation, and chronic inflammation. Extracellular vesicles (EVs), especially exosomes, have emerged as pivotal mediators of cell-to-cell communication with potential roles in both enhancing and alleviating aging. This review aimed to synthesize existing literature on the mechanistic and therapeutic role of EVs in aging and age-associated disorders. METHODS A comprehensive narrative review was performed utilizing Web of Science, Scopus, and PubMed databases. Studies assessing EVs in aging, cellular senescence, regenerative biology, and age-related disorders were included. Both preclinical and clinical studies were qualitatively examined, emphasizing EV origin, molecular pathways, and treatment outcomes. RESULTS EVs derived from young or stem cells show strong antiaging features across multiple systems, such as the immune, musculoskeletal, cardiovascular, and nervous systems. These impacts are regulated via mitigating cellular senescence, reestablishing mitochondrial activity, restoring mitophagic and autophagic signaling, regulating inflammatory signaling, and improving tissue regeneration. Contrarily, EVs from diseases or aged cells improve pro-aging phenotypes, such as inflammation, fibrosis, and metabolic dysregulation, underscoring their context-mediated duality. Preclinical evidence consistently supports EV-mediated therapies; nonetheless, clinical translation remains restricted owing to heterogeneity in EV subpopulations, lack of standardized isolation protocols, and variability in bioactive payload. CONCLUSION EVs represent promising therapeutic agents and biomarkers in aging biology, with the potential to regulate multiple hallmarks of aging concurrently. Prospective research should prioritize standardization, targeted bioengineering, and rigorous clinical validation to allow successful antiaging interventions.

From matrix to nucleus: CD44 as a central regulator of inflammaging, autophagy, and tissue homeostasis

cGAS–STING signaling in aging and age-related diseases: therapeutic promise and precaution

Evidence linking dysregulated cGAS–STING activation to inflammatory remodeling, senescence-associated changes, cell injury, fibrosis, and tissue dysfunction is synthesized, while highlighting the context-dependent roles of this pathway across physiological aging and ARDs.

Immune evasion of senescent cells: Mechanisms, pathological significance, and targeted interventions

Cellular senescence is a stress-induced cell-cycle arrest program accompanied by the senescence-associated secretory phenotype (SASP). While senescent cells are typically eliminated through immune surveillance under normal physiological conditions, they tend to accumulate progressively during aging and in chronic diseases. This review summarizes current evidence suggesting that such persistence is attributable not only to immune system decline but also to active, cell-intrinsic mechanisms of immune evasion. We discuss how senescent cells escape clearance by weakening immune recognition, suppressing phagocytic removal, resisting apoptosis, remodeling the inflammatory and structural microenvironment through SASP, and activating inhibitory checkpoint pathways in aged tissues. Furthermore, we investigate the contribution of these mechanisms to representative age-related diseases across multiple organs. Finally, we highlight emerging therapeutic strategies aimed at targeting the immune evasion of senescent cells, including checkpoint modulation, chimeric antigen receptor (CAR)-based cell therapies, vaccination approaches, and other immune-bypass strategies. Collectively, these insights underscore immune evasion as a critical determinant of senescent cell persistence and a promising target for interventions in aging and age-related diseases.

Multidimensional Regulatory Network of Cellular Senescence: From Mechanisms to Theranostics.