Aging & Longevity

Despite the effectiveness of combined antiretroviral therapy (ART), HIV infection remains a chronic condition characterised by persistent inflammation and immune activation, likely associated with viral persistence and other factors such as cytomegalovirus (CMV) co-infection. Long-acting (LA) injectable formulations, a newer class of ART with improved and sustained bioavailability, may help modulate the HIV-associated immunoinflammatory state. Therefore, we analysed dynamic changes in lymphoid...

The growing burden of aging-related disease and functional decline across Europe underscores the urgent need to optimize aging trajectories rather than simply extend lifespan. Achieving this goal requires identifying modifiable determinants that shape biological, psychological, and functional aging across the life course. Satisfaction with life (SWL) is emerging as one such integrative factor, linking adaptive capacity, resilience, and long-term healthspan outcomes. In this conceptual and...

Transcription by RNA polymerase II (RNAPII), which is essential for protein-coding gene expression and cellular function, is increasingly understood to become dysregulated with aging. Here, we use a multimodal approach to comprehensively characterize age-dependent changes in RNAPII-mediated transcription in both mouse and human tissues. Short-read total RNA sequencing (RNA-seq) to profile nascent transcription reveals a global reduction in overall transcriptional activity/frequency in aged...

Microbiota-derived metabolites are central mediators between commensal microbes and host immune system at mucosal barrier surfaces. Insights from mouse models have revealed precise molecular mechanisms by which numerous metabolites, including short-chain fatty acids, tryptophan catabolites and bile acid derivatives, regulate epithelial integrity, innate immune tone, and adaptive immunity and tolerance. Parallel studies in humans increasingly confirm these pathways and link metabolite...

CONCLUSIONS: In the multimorbidity management model for older adults, interventions such as patient peer support groups and case manager-led health education are proposed as theoretical strategies. These potential measures aim to support patient self-efficacy and facilitate health literacy, thereby potentially contributing to better overall health of patients.

CONCLUSIONS: There are distinct joint trajectories of physical frailty and social relationships among Japanese community-dwelling older adults. These trajectories are associated with different risks of long-term care needs, with the progressive frailty and rapid social relationships decline subgroup facing the greatest burden.

Macrophages are pivotal immune cells due to their phagocytic capabilities, yet the impact of aging on macrophage phagocytosis remains poorly understood. Using comprehensive in vitro and in vivo phagocytic assays, we demonstrate significantly reduced phagocytic activity in monocyte-derived macrophages from aged humans and mice compared to young counterparts. RNA-seq analysis revealed upregulated expression of extracellular matrix protein genes, particularly collagens, in aged macrophages;...

Myofibroblasts are morphologically similar cells with diverse origins that exhibit characteristics of both fibroblasts and smooth muscle cells. Following insults, myofibroblasts play critical roles in tissue reintegration and restitution. However, their prolonged presence and activity impede physiological recovery, leading to persistent or progressive tissue complications, as evidenced in corneal fibrosis and opacification. Reactive oxygen species (ROS) are key signaling intermediates in various...

Aging tissues experience a gradual decline in perfusion and metabolic resilience due to complex interactions among extracellular matrix (ECM) remodeling, vascular dysfunction, and mitochondrial impairment. Stiffening of the ECM that results from collagen crosslinking, elastin loss, and basement membrane thickening reduces vascular compliance and impairs local angiogenesis. The consequent reduction in capillaries and diminished endothelial reactivity leads to ongoing or intermittent hypoxia,...

Quantitative insights into brain metabolism are essential for advancing our understanding of the energy dynamics in the brain. Here, we present a nanowatt-resolution biocalorimeter capable of real-time metabolic heat output measurements of individual, live Drosophila melanogaster brains. Using this platform, we show that female brains, across multiple genotypes, exhibit a significantly higher metabolic rate (∼10%-15%) than male brains at a young age (<10 days old) and follow distinct metabolic...

Aging is the primary risk factor for most chronic diseases, and the global rise in aging populations presents an escalating challenge due to functional decline and multimorbidity. Gene therapy provides a versatile framework for modulating aging-regulatory pathways, such as epigenetic regulation, telomere maintenance, and stress-response networks, with the potential to reshape aging trajectories. In this review, we provide an in-depth synthesis of the genetic and epigenetic determinants of aging...

The human immune system undergoes dynamic remodeling from infancy through old age. We profiled PBMCs from 167 healthy individuals (ages 2 months to 105 years): infants (n = 36), children (n = 26), adolescents (n = 20), young adults (n = 24), middle‑aged (n = 16), older adults (n = 33) and oldest old (n = 12) using scRNA‑seq and snATAC‑seq (n = 23). MAIT and γδ T cells showed a "rise and fall" pattern, rising in childhood, peaking in young adulthood, and declining with age. Conventional CD8⁺ T...

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20-25% of individuals exhibited accelerated aging in a single cell type and 1-3% in 10 or more...

By measuring thousands of proteins in blood samples from over 60,000 people, we built molecular 'clocks' to estimate how fast cells age. Our analyses show that cell types age at different rates within the same person. Accelerated aging of specific cell types is associated with increased disease risk, whereas slower aging of others is linked to protection and improved survival.

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The brain and body undergo coordinated changes throughout the life span, yet studies of aging have traditionally examined these systems as separate entities. Here we ask how brain health relates to aging and peripheral biomarkers of metabolic and vascular function, including body mass index, blood pressure, and blood biochemistry. We use multivariate pattern learning to identify generalizable patterns of covariance between multi-modal neuroimaging data (structural, functional, diffusion, and...

Hypoxia is a common stress encountered by animal tissues during development, physiology, and disease. To cope with hypoxic stress, cells remodel metabolic and signaling networks to preserve viability and function. Lysosomes serve as central hubs for metabolic control and intracellular signaling, yet their role in hypoxic adaptation remains unclear. Here, we identify the lysosomal calcium transporter TMEM165 as a hypoxia-responsive regulator of cellular homeostasis. Under hypoxic conditions,...

ObjectivesThis study examined the influence of hearing status and loneliness on verbal fluency trajectories in adults aged 60 years and older, assessing their contributions to baseline performance and longitudinal change over time.MethodsData were drawn from 4,929 participants in the Health and Retirement Study (HRS) with objective hearing assessment in 2018 and three waves of semantic verbal fluency and loneliness measured in 2018, 2020, and 2022. Latent growth curve models were estimated to...