Major depressive disorder (MDD) is a risk factor for many aging-related medical conditions as well as cognitive decline and mortality. These and other types of observations indicate a premature aging phenotype associated with the conditions mentioned above. Recent studies have started to elucidate the mechanisms underlying the link between MDD and premature aging, pointing towards novel treatments of this phenotype. In this review, we first present evidence linking MDD to a premature aging phenotype and its association with abnormalities in multiple hallmarks of biological aging. Next, we discuss implications for treatment in MDD, including the potential geroprotective effects of antidepressant treatment as well as the conceptualization of biological aging processes as targets for novel gerotherapeutic interventions. Finally, we highlight the importance of integrating mental health assessment into both research and clinical settings to fulfill the promises of the new medical discipline of Geromedicine in preventing age-related decline and extending healthspan in the aging population.

Artificial intelligence (AI) has become a central driver in healthy longevity medicine (HLM), offering new tools to characterize biological aging trajectories, identify preclinical physiological decline, and optimize interventions aimed at preserving function throughout the lifespan by targeting age-related processes. HLM is increasingly recognized as a specialty focusing on the multidimensional process of aging, encompassing molecular, physiological, cognitive, and behavioral components, all of which generate complex, high-dimensional datasets that exceed the analytical capacity of traditional clinical approaches. AI methodologies, including machine learning and deep learning models capable of integrating large, multimodal data streams, provide the computational infrastructure required to produce actionable insights. In the clinical practice of HLM, AI further facilitates integration of converging domains, including continuous digital phenotyping enabled by wearables and sensors, advanced biomarker modeling, predictive modeling capable of forecasting risk trajectories and personalized intervention optimization through life models and digital twins. These models support anticipatory clinical management, shifting care from reactive disease treatment toward continuous preservation of physiological resilience. Despite rapid progress, the integration of AI into routine healthy longevity care requires careful consideration of data quality, algorithmic transparency, regulatory frameworks, population diversity, and clinical interpretability. Nonetheless, AI-driven healthy longevity management is beginning to allow biological aging to be quantified, targeted, and longitudinally monitored in clinical practice.

The decline in brown adipose tissue (BAT) activity is a hallmark of aging and is believed to contribute significantly to the loss of cold tolerance and the increased propensity for obesity with age. Paradoxically, unlike in many other tissues and organs, available evidence suggests that macroautophagy increases in BAT with aging. This aligns with observations of a negative correlation between thermogenic activity and macroautophagy in response to environmental factors such as ambient temperature, with evidence showing that macroautophagy is suppressed in thermogenically active BAT under cold conditions, and conversely, increased in warmer environments. Moreover, the activation of macroautophagy, particularly mitophagy, has been shown to be essential for the “whitening” process, whereby brown or beige adipose tissue loses its thermogenic phenotype and adopts characteristics of energy-storing white adipose tissue. In contrast, recent findings suggest that chaperone-mediated autophagy (CMA) is directly associated with BAT thermogenesis. In male mice, CMA tends to decline with age in BAT, and pharmacological activation of CMA can restore thermogenic activity. This may be due to a specific role of CMA in degrading thermogenesis-inhibiting factors that accumulate in aging BAT because of diminished CMA activity. Given the critical role of BAT in metabolic health, especially during aging, autophagic processes, and their potential druggability, emerge as a promising strategy to preserve thermogenic capacity and improve metabolic health in the elderly.

Age-related macular degeneration (AMD), primarily driven by dysfunction of the retinal pigment epithelium (RPE), is the leading cause of irreversible blindness in the elderly. As the central hub for photoreceptor support, nutrient transport, and waste clearance, the RPE is particularly vulnerable to age-related stressors that disrupt proteostasis and mitochondrial quality control. Autophagy and mitophagy are essential regulators of RPE and retinal longevity, ensuring the turnover of damaged proteins and organelles while maintaining energy homeostasis. In AMD, these pathways become compromised, contributing to lipofuscin accumulation, oxidative stress, inflammation, and progressive cell death. This review examines the physiological roles of autophagy and mitophagy in retinal homeostasis, their dysregulation in AMD, and emerging therapeutic approaches aimed at restoring these protective processes. Targeting autophagy and mitophagy is a promising strategy to preserve vision and delay the progression of AMD.

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.