Cancer recurrence remains a leading cause of mortality in patients with solid tumors. Early disseminated tumor cells (DTCs), which seed distant organs during the initial stage of tumor progression, are widely recognized as an important source of late metastatic relapse. Tumor cell dormancy, a reversible but prolonged non-proliferative state, enables DTCs to survive in metastatic tissues for years or even decades before re-entering the cell cycle and giving rise to overt metastases. Accumulating evidence indicates that dormancy is regulated by both cell-intrinsic mechanisms, such as epigenetic reprogramming and metabolic adaptation, and extrinsic cues from the tissue microenvironment. Among these extrinsic regulators, ageing has emerged as a critical determinant of DTC fate by profoundly remodeling tissue microenvironments through cellular senescence, chronic inflammation, extracellular matrix (ECM) remodeling, vascular dysfunction, stromal metabolic rewiring, and immune dysregulation. These ageing-associated alterations progressively erode dormancy-supportive niches, thereby leading to metastatic reactivation. In this Review, we summarize the molecular mechanisms governing tumor dormancy and discuss how ageing-associated microenvironmental remodeling contributes to the reactivation of dormant DTCs. We highlight the roles of the senescence-associated secretory phenotype (SASP), ECM remodeling, vascular deterioration, and organ-specific stromal ageing in regulating the maintenance and exit of tumor dormancy. We also discuss emerging translational opportunities, including dormancy-reinforcing therapies, senolytic strategies, liquid biopsy-based surveillance, and advanced experimental platforms such as single-cell and spatial technologies. Collectively, this Review provides a conceptual framework for understanding how ageing progressively modulates tumor dormancy and highlights potential strategies to prevent late metastatic recurrence.

Homologous recombination (HR) is a high-fidelity DNA double-strand break repair pathway that plays a central role in preserving genome stability and suppressing tumorigenesis. Core HR proteins, including CtIP, BRCA1, and RAD51, function in a tightly coordinated manner to mediate DNA end resection, pathway choice, and homology-directed strand exchange. Increasing evidence indicates that the abundance, activity, and chromatin engagement of these HR regulators are not constitutive but are dynamically controlled across multiple regulatory layers, including transcriptional programs, post-transcriptional RNA regulation, and post-translational proteostasis mechanisms. These regulatory systems integrate cell-cycle, stress signaling, and metabolic context to regulate HR capacity. In this review, we present an integrated framework describing how CtIP, BRCA1, and RAD51 are regulated across transcriptional, post-transcriptional, and post-translational levels, with an emphasis on mechanisms that jointly control multiple HR proteins as well as gene-specific regulatory modules.

YWHAG is a subtype of the 14-3-3 protein family that regulates the transduction of multiple signaling pathways in cells, such as the phosphoinositide 3-kinase–protein kinase B (PI3K-AKT) and mitogen-activated protein kinase (MAPK) pathways, by recognizing and binding to specific phosphorylated target protein motifs. These signaling pathways are widely found to be abnormally activated or shut down in human diseases, such as cancer and neurodegenerative diseases. Different evidence has shown that the expression levels and functions of YWHAG in different tumors are not the same. Meanwhile, the potential functions of YWHAG in these diseases and its role in regulating abnormal signaling pathways are still unknown. Therefore, further exploration and research are needed to determine YWHAG’s core role in regulating signaling pathways and whether YWHAG can be a therapeutic target for diseases to develop corresponding drugs. This review will revisit the structure and function of YWHAG, elaborate on the newly identified YWHAG-interacting proteins in recent years, summarize the functions of YWHAG in cancer while comparing it with the homologous family member YWHAZ, explore the functions of YWHAG in neurodegenerative diseases, and present our perspectives on drug-screening strategies targeting YWHAG.

Skin photoaging is a progressive, ultraviolet (UV)-driven form of extrinsic skin aging that compromises epidermal barrier integrity, dermal extracellular matrix organization, pigmentary homeostasis, and subcutaneous tissue support. Current findings indicate that photoaging is driven by interconnected molecular mechanisms, including ultraviolet A-(UVA)- and ultraviolet B (UVB)-induced reactive oxygen species (ROS) generation, DNA photolesions, mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1-) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated inflammatory signaling, matrix metalloproteinase activation, collagen and elastin degradation, mitochondrial dysfunction, autophagy impairment, and senescence-associated secretory phenotypes (SASP). Plant-derived polyphenols, carotenoids, and terpenoids primarily attenuate oxidative stress and inflammatory signaling; marine-derived mycosporine-like amino acids, sulfated polysaccharides, xanthophylls, and collagen peptides provide UV absorption, matrix protection, and structural support; and microbiome-derived metabolites and probiotics modulate redox balance, immune signaling, and barrier homeostasis via the gut-skin axis. By integrating layer-specific pathogenesis with multi-source natural interventions, this review highlights translationally relevant strategies for developing safer, mechanism-guided anti-photoaging therapies, informing both preclinical research and clinical applications.

Cellular senescence is a cell fate triggered by diverse endogenous and exogenous stresses, including DNA damage, telomere dysfunction, and metabolic dysregulation. It is characterized by irreversible cell cycle arrest and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). As a hallmark of ageing, senescence contributes to various physiological processes and is closely associated with the pathogenesis of age-related diseases. Specifically, senescent cells secrete SASP factors, which promote chronic inflammation, and propagate senescence to neighboring normal cells. DNA damage, a crucial inducer of cellular senescence and inflammation, often leads to the accumulation of cytosolic DNA. The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS-STING) pathway has emerged as a critical mechanism for detecting such intracellular DNA, and its excessive activation is strongly associated with senescence and age-related chronic inflammation (inflammaging). Accumulating evidence indicates that multiple factors can trigger cGAS-STING signaling, thereby stimulating inflammatory responses and accelerating cellular senescence. In this review, we summarize recent advances in understanding how cGAS-STING signaling orchestrates cellular senescence and inflammaging. We outline the key hallmarks and triggers of cellular senescence, with particular emphasis on the role of cGAS in age-related inflammatory diseases. Finally, we discuss that targeting the cGAS-STING pathway may pave new ways for therapeutic strategies to mitigate cellular senescence-associated diseases.

Operating as a physically and physiologically integrated unit, skeletal muscle and bone are fundamental to human mobility and metabolism. Their reciprocal crosstalk endures throughout life. In early embryonic development, with a primary focus on morphogenesis, skeletal muscle and bone actively drive the functional maturation of both tissues during development. When the interplay reaches relative homeostasis during adulthood, they reciprocally sustain the functional integrity and physiological homeostasis of one another. With aging, however, this intimate connection exacerbates reciprocal decline, initiating a pathological feed-forward loop that precipitates osteosarcopenia. As this crosstalk is orchestrated by a shifting matrix of mediators, from biomechanical loads to neuronal, immunological, and secretory signals, understanding their age-associated alterations may help provide a point of intervention for treatment. This review outlines dynamic changes in muscle-bone crosstalk throughout the lifespan, discusses longitudinal changes in aging, and provides stage-specific perspectives for intervention.

Frailty, a geriatric syndrome marked by multisystem functional decline and heightened vulnerability, threatens older adults’ health span. Immunosenescence and chronic low-grade inflammation are increasingly recognized as core drivers, with age-related impairments in cellular, humoral, and innate immunity disrupting immune homeostasis. Tertiary lymphoid structures (TLS), ectopic immune aggregates that orchestrate local immune responses, have emerged as candidate regulators in chronic disease, yet their role in frailty remains largely unexplored. Here, we propose a conceptual framework for frailty pathogenesis in which immunosenescence and chronic low-grade inflammation (inflammaging) may act as upstream biological drivers associated with systemic lymphatic dysfunction, potentially contributing to the structural and functional dysregulation of TLS, a candidate intermediate tissue-level histological link. TLS dysfunction may subsequently contribute to multi-organ functional decline and the progression of frailty. We synthesize current evidence on the dynamic characteristics of TLS in aging, discuss TLS as candidate biomarkers and putative therapeutic targets for frailty, and highlight intervention strategies including molecular modulation, lymphatic function enhancement, immunotherapy, and lifestyle modifications. This tissue-level perspective highlights TLS as a potential histological link connecting immunosenescence, lymphatic dysfunction, and frailty, offering novel avenues for geriatric precision medicine and the development of immune-targeted interventions to delay frailty progression.