Aging & Longevity

Adult resident stem cells are capable of regenerating tissues that manifest signs of "rejuvenation" in flatworms and mice of older ages. These findings suggest potentially conserved regulatory mechanisms of adult resident stem cells from worms to mammals. Regenerative capacities are more limited in specific tissues and stem cell types of larger mammals. Understanding and harnessing the rejuvenating properties of resident adult stem cells in flatworms and mice could have broad therapeutic...

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunction and non-motor symptoms affecting cognition, mood and autonomic function. Both genetic susceptibility and environmental exposures such as pesticides (e.g., paraquat, rotenone), heavy metals (e.g., manganese, lead), tobacco smoke, and caffeine have been implicated in PD pathogenesis. Recent studies highlight the role of epigenetic mechanisms including DNA methylation (e.g., SNCA, PARK2), histone...

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Obesity is linked to an increased risk of various lung disorders, yet its role in disease progression remains poorly understood. We have utilized multiomics approaches together with functional assays to explore the effect of obesity on the lung. Obesity induced matrisome remodeling and structural alterations in the elastic fiber network, exhibiting solubility shifts that overlapped with those seen in the aging lung. In addition, protease inhibitor levels were reduced in lung tissue and...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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).

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.