Skin diseases affect nearly one quarter of the global population, with prevalence rising sharply among older adults. By 2050, the number of individuals over 60 years will double, making age-related dermatological conditions an increasing public health concern. A central process underlying aging is cellular senescence, a stable form of growth arrest induced by diverse stressors, including DNA damage, telomere attrition, and oncogenic signaling. Senescent keratinocytes, fibroblasts, melanocytes, and immune cells accumulate in the skin with age and secrete a pro-inflammatory senescence-associated secretory phenotype (SASP) that actively shapes the cutaneous immune landscape. Although senescence can promote tissue repair and tumour suppression, the persistence of senescent cells drives inflammation, impairs immunity function, and contributes to pathology, a concept now termed senopathy. In this review, we first examine the crosstalk between senescent stromal and immune cells in human skin. Then we discuss how SASP from senescent fibroblasts inhibits the function of resident T cell, while senescent T cells adopt a paradoxical state, hyperfunctional yet non-proliferative, that can accelerate tissue damage. We further highlight the immune evasion strategies which enable senescent cells to persist and drive inflammaging. Insights from patients with Familial Melanoma Syndrome (germline CDKN2A mutations) illustrate how defective senescence pathways across multiple cell types impair cutaneous immunosurveillance and increase melanoma risk. Finally, we explore evidence for stromal- and immune-mediated cutaneous senopathies, including psoriasis, lupus, vitiligo, and leishmaniasis, where senescent cells actively drive the diseases’ progression. Based on the analysis, we propose that the skin represents a powerful and accessible model for investigating the interplay between senescent immune and non-immune cells across the lifespan, with therapeutic implications for aging and age-related pathologies.

With increasing chronological age, the vascular system gradually loses its functional integrity, a process known as vascular aging. This decline is a major contributor to arterial and venous thromboembolic disorders, which represent one of the leading causes of mortality and morbidity among aged individuals. However, the precise biological mechanisms linking systemic aging to thrombotic susceptibility remain poorly understood, hindering the development of effective preventive and therapeutic strategies for age-related thrombotic diseases. Aging, as a fundamental determinant of vascular health, shifts the balance between prothrombotic and antithrombotic mechanisms through cumulative molecular and cellular alterations across vascular cells, red blood cells, platelets, and immune cells. These interconnected hallmarks collectively disrupt endothelial homeostasis, enhance platelet reactivity, and impair coagulation and fibrinolytic pathways. Emerging factors, including clonal hematopoiesis of indeterminate potential and environmental exposures, further exacerbate the thrombotic risk in older populations. Clinically, thrombosis management in the elderly requires careful calibration between protection against ischemia and bleeding risk, as age-associated changes are known to affect the safety and efficacy of antiplatelet and anticoagulant therapies. The development of geroscience-guided interventions, alongside optimized antithrombotic strategies, will be essential to reduce the thrombotic burden and improve outcomes in the aging population.

The Hippocratic Oath enshrines the ethical imperative primum non nocere -“first, do no harm”- thereby guiding medicine practice toward the meticulous avoidance of interventions that may compromise patients’ physiological integrity and overall well-being. Following this principle, benzodiazepines were initially introduced as safer alternatives to barbiturates and have since become one of the most commonly prescribed drug classes for the long-term management of neuropsychiatric disorders in older adults with progressive health deterioration. However, emerging evidence implicates the endogenous benzodiazepine-like peptide, acyl-CoA binding protein/diazepam-binding inhibitor, in the orchestration of maladaptive stress responses. These responses are associated with accelerated pathological aging and increased risks of a spectrum of age-associated morbidities, including metabolic syndrome, cardiovascular diseases, cancers, and immune dysfunction. Corroborating these mechanistic insights, retrospective observational studies have consistently reported significant correlations between long-term benzodiazepine use and elevated risks of cardiovascular mortality, dementia, cancer incidence, impaired responsiveness to immunotherapy, and heightened vulnerability to severe infections. Given these converging lines of evidence, we strongly advocate for the cautious reduction of benzodiazepine prescriptions in elderly patients. Whenever clinically feasible, these agents should be replaced by alternative psychotropic compounds with more favorable risk-benefit profiles, in alignment with contemporary standards of geriatric pharmacotherapy and the ethical imperative to minimize iatrogenic harm.

Significant progress in clinical care has extended human life expectancy to unprecedented levels. However, this trend has been parallelled by a rise in years lived with poor health, posing profound challenges not only to individual quality of life, but also to substantial medical and socioeconomic burdens at the population level. This underscores the urgent need for strategies that extend healthspan alongside lifespan. In this regard, nicotinamide adenine dinucleotide (NAD⁺) has emerged as a central metabolic cofactor and signaling molecule that regulates processes fundamental to health and longevity, including energy metabolism, mitochondrial function, inflammation, and DNA repair. Importantly, intracellular NAD⁺ levels decline with age across multiple tissues and organ systems, and restoring NAD⁺ content has been shown to reinstate cellular and physiological function in various model systems. Among the strategies to augment NAD⁺, supplementation with its precursors, namely nicotinic acid/niacin, nicotinamide, nicotinamide riboside, and nicotinamide mononucleotide, represents the most practical and extensively studied approach. Over the past two decades, preclinical research and an increasing number of clinical trials have investigated the therapeutic potential of these precursors in preventing or reversing age-associated decline and pathologies. In this review, we synthesize recent clinical advances, critically evaluate the promise and limitations of NAD⁺ precursor supplementation, and discuss future directions for leveraging NAD⁺ metabolism to improve healthspan in a rapidly aging global population.

The biology of aging is increasingly understood through geroscience frameworks integrating molecular, cellular, physiological, and social hallmarks. Recently, we introduced psychosocial factors including mental illness as an important hallmark of aging. Indeed, exposome-centered approaches reveal complex interactions among socioeconomic, environmental, behavioral, and genomic factors. Precision Geromedicine aims to target all these determinants in a holistic fashion to improve aging trajectories and extend healthspan.

In recent years, the terms “gerosuppressors” and “gerogenes” have been introduced to describe factors that respectively delay or accelerate aging. These factors are present across various cell types. Specific proteins, such as tau predominantly expressed in neurons, may act as neuron-specific gerosuppressors or gerogenes. Tau exhibits a dual role influenced by its post-translational modifications, particularly phosphorylation. In this review, we discuss relevant examples of tau isoforms that demonstrate both roles, underscoring its dual influence on neuronal aging.