Aging & Longevity

Cerebrospinal fluid (CSF) continuously circulates through the brain and surrounding tissues to remove metabolic waste, a process that becomes less efficient with ageing and in neurodegenerative disease. Visualizing this drainage in living animals has been difficult because existing imaging tools either lack depth, require radioactive tracers, or are too slow to capture dynamic flow. Here, we show that whole-body photoacoustic computed tomography (PACT) enables three-dimensional, real-time...

"Inflammaging", the chronic increase in inflammatory signaling with age, remains poorly understood in hematopoietic aging. Here, we identify the innate immune RNA sensor melanoma differentiation-associated protein 5 (MDA5) as an important factor of hematopoietic stem cell (HSC) aging. Aged Mda5^(-/-) mice exhibit reduced HSC accumulation and myeloid bias. Importantly, aged Mda5^(-/-) HSCs retain greater quiescence and superior repopulation capacity in noncompetitive transplants compared to...

This study investigated whether higher cardiorespiratory fitness (VO₂peak) is associated with better cerebral vascular and metabolic health-specifically cerebral blood flow (CBF), cerebrovascular reactivity (CVR), cerebral metabolic rate of oxygen (CMRO₂), and oxygen extraction fraction (OEF) across healthy older adults and patients with coronary artery disease (CAD). Thirty-seven healthy adults (65.3 ± 8.3 years old) and 35 CAD patients (66.4 ± 9.3 years old) underwent calibrated fMRI using...

Although population aging is a global worldwide phenomenon, it is most pronounced in European Union countries. An unhealthy ageing population not only places a heavy burden on healthcare, but also hinders sustainable socio-economic development. Supporting healthy aging can be achieved through evidence-based strategies aimed at reducing avoidable mortality and interventions that promote these strategies. Our study is based on a secondary analysis of Eurostat data for 2022 to describe the extent...

Alterations in biological rhythms are a common feature of aging, and disruption of circadian rhythms can exacerbate age-associated pathologies. The retina is critical for detecting light for both vision and for transmitting time-of-day information to the brain, synchronizing rhythms throughout the body. Disruption of circadian rhythms by manipulating the molecular clock leads to premature retinal degeneration in flies and mice, and gene expression rhythms are altered in models of age-associated...

Frailty emerges as the intermediate stage preceding disability, but there is a gap in molecular signatures for early detection of subclinical cellular changes, which could help predict frailty onset or the effectiveness of interventions. In this randomized, controlled study, we assessed phenotypical and functional changes in frail individuals before and after a 6-month multidomain lifestyle intervention (nutritional supplement and supervised exercise) vs habitual care. We also analyzed...

Heat hormesis describes a biphasic, dose-dependent response in which low levels of heat stress induce beneficial effects, such as enhanced lifespan and stress resilience. This phenomenon is commonly studied in Caenorhabditis elegans using regimens that involve mild heat stress priming, followed by a recovery period and subsequent stress challenge or lifespan measurement. The concept is conserved across species and has gained renewed interest due to its potential relevance to therapeutic...

Frailty is a significant health issue among older adults. Oxidative stress (OS), indicated by elevated malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) activity, is implicated in age-related diseases. This study aims to explore the relationship between OS biomarkers, MDA and SOD, and frailty among older adults. This study investigated the association between MDA, SOD, and frailty in 3181 older adults from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Frailty was...

CONCLUSIONS: Moderate and high-intensity PA were associated with lower odds of falls, with important effect modification by cognitive status and health symptoms. These findings suggest that fall prevention strategies should account for cognitive function and symptom burden when promoting physical activity in older adults.

CONCLUSIONS: Bridging the willingness-utilization gap requires systemic reform across policy, organizational, service, and individual levels. Priorities include expanding LTCI eligibility, formalizing volunteer roles within interdisciplinary teams, establishing navigation mechanisms for unmet "grey-zone" needs, and enhancing digital literacy through hybrid information systems. By extending Haggerty's continuity framework beyond clinical care, this study illustrates how volunteers can be...

CONCLUSIONS: An in-home mobile integrated health (MIH) transitional care program for frail older adults after hospital discharge was associated with lower 30-day readmission rates. These findings highlight MIH as a promising model to support aging in place and suggest its potential value for adoption within age-friendly health systems.

Mitochondrial quality control is tightly associated with aging-related neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Previous studies reported that ALS/FTD-associated protein p62 drives "mitochondrial clustering" (perinuclear clustering of fragmented and swollen mitochondria) during PINK1/Parkin-mediated mitophagy, but the underlying molecular mechanism, especially the precise role of p62 in...

Aging is the primary risk factor for many neuromuscular (NM) diseases that impair motor and cognitive function. Transplantation of young muscle-derived stem/progenitor cells (MDSPCs) has shown remarkable therapeutic potential across a range of age-related diseases, primarily through paracrine mechanisms. In this study, secretome profiling of young MDSPCs revealed a unique enrichment of pro-angiogenic and immunomodulatory proteins compared to their aged counterparts. Our systemic transplantation...

Immunotherapeutic approaches to brain aging remain largely preclinical and in early translational stages, and they have focused mostly on modulating innate immunity. In this issue of Immunity, Negredo et al. identify T cells bearing exhaustion-like signatures as a hallmark of brain aging and reveal the beneficial effects of an engineered IL-10 variant that functionally uncouples pro- and anti-inflammatory signaling in microglia.

Counteracting cognitive decline is a declared goal of regenerative medicine. Recently, partial cellular reprogramming has emerged as a promising strategy to promote tissue regeneration and restore cellular function, but whether this approach bears fruit when targeted to cell populations underlying cognitive processes remains unknown. Here, we report that partial reprogramming of engram neurons-bona fide memory trace cells-by OSK-mediated gene therapy reversed the expression of senescence- and...

Posttraumatic stress disorder (PTSD) is associated with accelerated biological aging. In general, psychological resilience is related to more normative aging patterns; however, among individuals with PTSD, resilience may be associated with older biological aging. For example, prior work suggests that individuals with PTSD who have higher psychological resilience show more advanced epigenetic aging than individuals with lower psychological resilience. We investigated whether psychological...

BACKGROUND: Mobility loss in older adults reduces quality of life and increases risks of falls, hospitalizations, and mortality. Low-functioning (LF) older adults experience faster mobility decline than their high-functioning (HF) peers, but the underlying biological mechanisms remain unclear. Although iron accumulation in aging muscle mitochondria has recently been linked to lower physical function, its longitudinal impact on physical function remains understudied.

CONCLUSIONS: This study depicts the metabolic features of MASLD in the older population. Our finding explores promising biomarkers for diagnosis and provides more perspectives on molecular mechanisms and potential targets for MASLD in the context of aging.

Sleep is viewed typically through a brain-centric lens, with little known about the role of the periphery^(1,2). Here we identify a sleep function for peripheral macrophage-like cells (haemocytes) in the Drosophila circulation, showing that haemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in haemocytes, we discovered that knockdown of eater-a member of the Nimrod...

Nucleotide excision repair (NER) removes bulky adducts from genomic DNA and prevents the ultraviolet light-sensitivity disease xeroderma pigmentosum, cancer and premature ageing¹. After initial lesion recognition by XPC in global genome repair or by stalled RNA polymerases in transcription-coupled repair, a lesion and surrounding DNA duplex are unwound by TFIIH, which includes the ATPases XPB and XPD, and additional NER factors XPA, XPF, XPG and RPA, to form a DNA bubble² comprising around 27...