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 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.

Aging is a key risk factor for cancer, with complex, context-dependent processes influencing both tumor initiation and progression. While certain aging-associated processes restrain cellular proliferation, others drive tumor initiation and progression, revealing a context-dependent duality in the role of aging in cancer. Increasing evidence indicates that many of these transitions occur not through genomic alterations, but through reprogramming of protein post-translational modifications (PTMs). Phosphorylation, ubiquitination, acetylation, methylation and an expanding repertoire of acylations collectively regulate protein activity, stability, localization and interactions, translating aging-associated stresses, including metabolic imbalance, microenvironmental remodeling and accumulated damage, into functional cellular outcomes. In this review, we examine how PTMs bridge aging and cancer through three interconnected axes: integration of stress signals, encoding of metabolic states, and modulation of the tissue microenvironment. We discuss how major PTM systems coordinate core cellular processes, such as checkpoint control, proteostasis, chromatin organization and cell–environment communication, and how, through dynamic and combinatorial actions, they establish distinct regulatory states that determine whether tissues sustain homeostasis, progress to dysfunction, or undergo malignant transformation. An in-depth understanding of how PTMs define these states provides valuable insights into disease stratification and offers new avenues for therapeutic interventions.