Aggregator

The accumulation of senescent cells contributes to age-related inflammation and heightened susceptibility to viral infection. The mechanisms by which cellular senescence and aging exacerbate virus-associated diseases remain poorly understood. Here we show that innate antiviral immunity is progressively impaired with aging in mice, in parallel with systemic accumulation of senescent cells. Mechanistically, senescent cells suppress innate antiviral response mostly via four senescence-associated...

This article aims to comprehensively analyze the vascular factors in Alzheimer's Disease (AD), particularly the changes in the carotid arteries, and their complex correlations with hippocampal atrophy and cognitive function. Besides the traditional β-amyloid protein (Aβ) and Tau protein hypotheses, vascular factors are increasingly regarded as crucial factors in the development of AD. This article systematically reviews the roles of cerebral blood flow perfusion changes and micro-infarctions in...

The accumulation of amyloid β (Aβ) protein in the brain is a central pathological hallmark of Alzheimer's disease (AD). This process has become a major focus of interdisciplinary research and a critical target in drug development. Aβ is produced through the proteolytic processing of amyloid precursor protein (APP) by a group of enzymes known as secretases. They belong to different protease classes and operate through proteolytic cleavage of the peptide bond through several catalytic hydrolysis....

Gait speed is a robust marker of health in older adults and is associated with cognition, yet few studies have examined this in the oldest-old and if there are differences by cognitive domain. We examined the association between gait speed and cognition across three domains in individuals aged 90 + , considering differences by gender and device use. Then, 502 participants were included from the LifeAfter90 Study. Baseline gait speed (meters/second) was measured using the 4-meter walk test. The...

CONCLUSIONS: SHARED delivers a comprehensive, multidimensional framework for social health and provides strong multi-cohort evidence of its importance for cognitive ageing and dementia. Findings highlight the need for improved social health measurement and further work to disentangle its mechanisms and bidirectional links with cognitive ageing and dementia.

The lymphatic system is essential for maintaining interstitial fluid balance, supporting immune surveillance, and clearing metabolic waste, yet its role in ageing has only recently come into focus. With age, lymphatic vessels and lymphoid organs undergo structural and functional decline, leading to impaired transport, disrupted immune cell trafficking, and chronic low-grade inflammation. These changes contribute to systemic inflammaging and are increasingly implicated in cardiovascular disease,...

CONCLUSIONS: This study presents a comprehensive multimodal, cell-type-resolved atlas of the human heart, providing a foundation for understanding human cardiac gene regulation across the human lifespan and in cardiac diseases.

Action cancellation declines with age, contributing to impairments in executive function and overall motor performance. While age-related deterioration of reactive inhibition (stopping an action in response to an external signal) is well-established, less is known about how ageing affects proactive inhibition (preparatory mechanisms which increase the chance that an action can be successfully stopped). This study examined how proactive and reactive inhibitory processes, assessed via changes in...

No abstract

Chronic stress (CS) exacerbates anxiety and hyperglycemia, emerging as a key risk factor for type 2 diabetes, yet the mechanism remains unclear. Here, we found that CS induces hyperglycemia and enhanced amygdaloid astrocytic senescence in mice. The amygdaloid astrocytic senescence was mediated by the reduction of hexokinase 2 (HK2) driven by pre-B cell leukemia homeobox transcription factor 1 (PBX1). The astrocytic Hk2 deletion mice and amygdala-specific astrocytic Hk2 knockdown mice both...

Cellular senescence is a conserved stress-responsive program defined by durable proliferative arrest and extensive remodeling of chromatin, metabolism, intercellular signaling, and immune interactions. Initially described as a barrier to unlimited cell division, senescence is now recognized as a pleiotropic and heterogeneous biological process with roles in development, tissue repair, immune surveillance, tumor suppression, aging, fibrosis, and cancer progression. Despite its broad relevance,...

The vascular endothelium performs numerous regulatory functions that impact inflammatory responses, thrombosis, vascular tone and angiogenesis. Endothelial dysfunction is a key contributor to the pathogenesis of various human diseases, either as a primary trigger or as a consequence of organ damage. This review examines how ageing reshapes endothelial cell metabolism and mitochondrial function, progressively undermining endothelial homeostasis and resilience. Age-related endothelial alterations,...

Interventions to extend lifespan and healthspan are of major interest, but such interventions may affect male and female organisms differently. Whether this is due sex-specific differences in baseline lifespan, or differences in sexually dimorphic characteristics such as body size, adiposity, metabolism, or even gonadal hormone or chromosome status remains unknown. Here we discuss the literature on how males and females respond differently to various types of interventions known to extend...

Nuclear receptors (NRs), a superfamily of ligand-activated transcription factors, serve as master regulators linking signaling molecules to the genome, coordinating a variety of essential physiological processes in development, homeostasis, metabolism, and reproduction. As the central biological sensors, NRs respond to a wide range of endogenous substances and xenobiotics, thereby orchestrating critical processes such as metabolic homeostasis, inflammatory and immune responses, cellular...

Extracellular matrix (ECM), once regarded as a passive structural scaffold, is now recognized as a key hallmark of aging. In the context of female reproductive aging, ECM remodeling acts as a pivotal driver of functional deterioration. This review outlines how age-associated ECM alterations, including collagen cross-linking, elastin degradation, and perturbed biomechanics, orchestrate ovarian aging through the mechanical activation of Hippo signaling, compromise endometrial receptivity via...

Aging clock models have emerged as a crucial tool for measuring biological age, with significant implications for anti-aging interventions and disease risk assessment. However, human aging clock models that offer single-cell resolution and account for cell and tissue heterogeneities remain underdeveloped. This study introduces scAgeClock, a novel gated multi-head attention neural network-based single-cell aging clock model. Leveraging a large-scale dataset of over 16 million single-cell...

The muscle-tendon junction (MTJ) is a specialised interface between muscle and tendon and transmits muscle-generated force to the tendon. The MTJ is particularly vulnerable to injuries compared to muscle and tendon and becomes more injury prone with age. Despite its clinical importance, the mechanisms driving MTJ ageing and age-related functional deterioration remain poorly understood. In this study, young (3-month-old) and old (23-month-old) male mice were used to provide the first...

CONCLUSION: Findings suggest a substantial burden of multimorbidity in NORC residents and reinforce the importance of designing programs in NORCs to help older adults with multimorbidity age in place.

The aging of the vasculature is a primary determinant of cardiovascular disease risk and a key contributor to organismal decline. While our understanding of its molecular underpinnings has grown exponentially, the translation of these discoveries into effective clinical interventions remains a major hurdle. This review provides a critical appraisal of the current state of vascular aging pharmacology. We first dissect the core pathogenic mechanisms, including epigenetic drift, chronic low-grade...

CONCLUSION: A highly efficient and cost-effective PND model was successfully established in 4-month-old SAMP8 mice. This model stably recapitulates core PND pathologies and serves as a valuable tool for investigating pathogenesis and screening therapeutic strategies for PND.