Aging & Longevity
Urolithin a modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing
Mitochondrial dysfunction and impaired mitophagy are hallmarks of aging and age-related pathologies. Disrupted inter-organellar communication among mitochondria, endoplasmic reticulum (ER), and lysosomes, further contributes to cellular dysfunction. While mitophagy has emerged as a promising target for neuroprotection and geroprotection, its potential to restore age-associated defects in organellar crosstalk remains unclear. Here, we show that mitophagy deficiency deregulates the morphology and...
Association of Eating Window With Mortality Among US Adults: Insights From a Nationally Representative Study
Time-based diets have gained popularity for their health benefits, but their effects on human longevity remain unclear, with most evidence from short-term human trials and animal studies. We determined the associations between eating window and mortality among U.S. adults. We conducted a prospective cohort study using NHANES 2003-2018 data linked to mortality records through December 2019. The analytic sample included 33,052 adults (aged 20 and above) with two complete 24-h dietary recalls...
Potential Connections Between Senescence and Chemobrain: An Early Overview of Literature
Chemotherapy-induced cognitive impairment (CICI), commonly referred to as chemobrain, is a pervasive adverse effect of cancer treatment, characterized by deficits in memory, concentration, and executive function. Several observations have suggested a potential for senescence in mediating CICI. First, chemotherapeutic agents that are implicated in CICI can also trigger senescence in neurons and glial cells, accompanied by the senescence-associated secretory phenotype (SASP), that could propagate...
Prevalence of Subjective Cognitive Decline Among Older Multiracial Adults, 2019-2023
Background: The Multiracial population is the fastest-growing racial group in the United States but remains underrepresented in cognitive aging research. No national estimates exist for subjective cognitive decline (SCD)-a self-reported indicator of worsening memory associated with dementia risk-among older Multiracial adults. Methods: We used 2019-2023 Behavioral Risk Factor Surveillance System data from states that administered the optional cognitive decline module (n = 599,874 adults aged...
The prevention of adult cardiovascular disease must begin in childhood: evidence and imperative
Growing evidence from the past seven decades indicates that atherosclerosis begins in youth and progresses in response to exposure to cardiovascular risk factors, which contribute to the development of cardiovascular disease in later life. A long-term randomized clinical trial lasting at least 50 years and involving screening and follow-up of children across their lifespan would provide the highest level of evidence to determine the lifelong influence of cardiovascular risk factors on...
Association and predictive values of nine biological age measures for cardiovascular disease mortality: screening and validation from two prospective cohort studies
Biological age (BA) reflects the aging process more accurately than chronological age. This study aimed to evaluate the associations and predictive values of nine BA measures for mortality outcomes. BA measures were developed using data from the Yixing Cohort Study (YCS; N = 4,128) and externally validated in the Jurong Cohort Study (JCS; N = 16,652). Dose-response relationships between the clinical indices and all-cause death were assessed using restricted cubic spline analysis. Statistically...
The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease
Immunosenescence is the process of immune dysfunction and gradual deterioration of the immune system associated with aging, while cellular senescence is the stable cell cycle arrest that can occur in non-immune or immune cells in response to stress or damage. Immunosenescence significantly impacts both the innate and adaptive immune responses and is characterised by physical changes in lymphoid organs, as well as dysfunctions in cellular and molecular mechanisms. Key features of immunosenescence...
Enhancing peripheral nerve regeneration in aging: the role of Schwann cells, c-Jun, and emerging therapeutic strategies
Peripheral nerve injuries (PNI) present a significant challenge, particularly in aging populations where Schwann cell dysfunction, reduced c-Jun expression, increased senescence, and impaired myelin clearance hinder regeneration. Targeted therapies aim to restore Schwann cell plasticity and improve nerve repair. These include gene therapy to upregulate c-Jun, senolytic agents to eliminate senescent Schwann cells, pharmacological activation of JNK, ferroptosis inhibition, and stem cell-based...
Use of Factor XI/XIa Inhibitors in Patients with Atrial Fibrillation: Current Progress and Future Prospects
Stroke prevention is one of the pillars of management in elderly patients with atrial fibrillation (AF), hence effective and safe anticoagulation strategies are needed. While available anticoagulants target coagulation factors involved in thrombus formation, their bleeding complications and limitations in aging populations underscore the necessity for novel agents. Factor XI/XIa (FXI/XIa), which selectively targets the intrinsic coagulation pathway, offers a promising approach by attenuating...
Latent Cognitive Profiles Predict 1-Year Mental Health, Insomnia, Falls, Daily Functioning, and Pain in US Older Adults: A National Longitudinal Study
CONCLUSIONS AND IMPLICATIONS: Even among cognitively intact older adults, subtle global cognitive decline predicted higher risk of depressive symptoms, anxiety symptoms, insomnia, falls, and impaired daily functioning. Profiles with orientation deficits were vulnerable to depression, shopping, and banking difficulties, whereas global impairment with preserved orientation was linked to increased anxiety symptoms. Implementing early cognitive screening for cognitively intact older adults and...
Social exposome and brain health outcomes of dementia across Latin America
A multidimensional social exposome (MSE)-the combined lifespan measures of education, food insecurity, financial status, access to healthcare, childhood experiences, and more-may shape dementia risk and brain health over the lifespan, particularly in underserved regions like Latin America. However, the MSE effects on brain health and dementia are unknown. We evaluated 2211 individuals (controls, Alzheimer's disease, and frontotemporal lobar degeneration) from a non-representative sample across...
Treatment of a severe vascular disease using a bespoke CRISPR-Cas9 base editor in mice
Pathogenic missense mutations in the alpha actin isotype 2 (ACTA2) gene cause multisystemic smooth muscle dysfunction syndrome (MSMDS), a genetic vasculopathy that is associated with stroke, aortic dissection and death in childhood. Here we perform mutation-specific protein engineering to develop a bespoke CRISPR-Cas9 enzyme with enhanced on-target activity against the most common MSMDS-causative mutation ACTA2 R179H. To directly correct the R179H mutation, we screened dozens of configurations...
Biomarkers of ageing of humans and non-human primates
Ageing is characterized by progressive functional decline and increase in disease risk and imposes substantial burdens on human health. Identifying aging biomarkers in primates is crucial for advancing our understanding of human ageing and for informing interventions to mitigate age-related pathologies. However, a comprehensive grasp of these biomarkers is still lacking, hindering the translation of fundamental research into clinical practice. In this Review, we present the current knowledge on...
Cognitive training gain transfer in cognitively healthy aging: per protocol results of the German AgeGain study
INTRODUCTION: Cognitive decline is part of the normal aging process, but also a major risk factor for dementia. Cognitive training interventions aim to attenuate cognitive decline, but training gains need to be transferable to untrained cognitive abilities to influence everyday function. Furthermore, the neurobiological basis of cognitive training gain transfer remains elusive. A possible candidate is increased bilateral hemisphere usage enabled by efficient structural connectivity, especially...
Cognitive flexibility in aging: the impact of age range and task difficulty on local switch costs in task switching
INTRODUCTION: Previous studies provided inconclusive results regarding the effects of aging on the ability to flexibly switch between task rules (local switch cost). The goal of the present study was to investigate the influence of age on the local switch costs at two levels of difficulty (easy task switching: two task rules vs. difficult task switching: four task rules).
Hand dexterity and mobility independently predict cognition in older adults: a multi-domain regression analysis
CONCLUSION: Hand dexterity (NHPT) and specific functional mobility tasks (5CRT, 4MWT) are robust, independent predictors of cognition in older adults. Grip strength, balance, usual gait speed, and gait variability offer limited additional value when assessed together. The NHPT and timed SPPB components are accessible, pragmatic tools for motor-cognitive research and screening.
Coordination of autophagosome closure and release by the Alzheimer's disease-associated protein BIN1
Autophagosome closure by the endosomal sorting complex required for transport (ESCRT) complex is a prerequisite for their dynamin 2 (DNM2)-dependent release from the recycling endosome and subsequent lysosomal clearance. However, the mechanism that coordinates autophagosome closure and release is unknown. We identified that the Alzheimer's disease-associated protein bridging integrator 1 (BIN1) is a critical mediator of this coordination. Prior to autophagosome closure, BIN1 is held at...
Oxytocin signaling regulates maternally directed behavior during early life
Oxytocin is essential in shaping social behavior across the lifespan. Although the role of oxytocin signaling in parental care has been widely investigated, little is known about its function in social behavior during early life. We studied the role of oxytocin in mouse pup social behavior during acute separation from the mother as well as upon reunion. The activity of oxytocin neurons was increased by acute maternal separation. Behaviorally, maternally separated pups emitted more ultrasonic...
Effects of age and musical training on resting-state periodic oscillatory brain activity
Neural oscillations comprise periodic and aperiodic components, which have been linked to cognitive functions. Changes in oscillatory activity as a function of age and musical training may related to cognitive decline and the protective effects of lifelong musical training. However, there are inconsistencies in prior studies assessing the changes in alpha oscillations with age and musical training experience, which did not consider the putative impact of the aperiodic activity. In this study, we...
ApoD mediates age-associated increase in vulnerability to influenza virus infection
Influenza A virus (IAV) infection causes significantly greater morbidity and mortality in the elderly population, but the molecular mechanisms in the aging process responsible for severe infection remain unclear. In this study, we found that increased severity in IAV infection and reduced innate immune response correlated with extensive mitophagy in senescent human cells and in the lung of aged mice. Apolipoprotein D (ApoD) was identified as strongly elevated in the lungs and sera of aged human...
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