Aging & Longevity

eccDNA is a driver of many cancers and a potential intermediate in other age-related disorders. However, little is known about the mechanisms underlying eccDNA formation in healthy tissue and how aging affects these processes. Here, we present an atlas of eccDNA across seven tissues of male mice spanning four ages. EccDNA correlates with open chromatin characterized by signatures of H3K27ac and H3K4me1. Additionally, the mutational load of eccDNA on genes correlates with tissue-specific...

Ageing is associated with cognitive decline, which is a significant factor in the development of dementia. Vitamin B12 (VB12) is crucial for maintaining proper nervous system function, as well as for protein, fat, and carbohydrate metabolism, and DNA synthesis. Moreover, it helps prevent serious health conditions such as pernicious anemia, neurodegenerative diseases, and Alzheimer's disease. VB12 deficiency is common among the elderly population. We found that serum VB12 levels were...

Therapy-induced senescence (TIS) alters calcium (Ca²⁺) flux and Mitochondria-ER Contact Sites (MERCS), revealing critical vulnerabilities in senescent cells. In this study, TIS was induced using Doxorubicin and Etoposide, resulting in an increased MERCS contact surface but a significant reduction in ER-mitochondria Ca²⁺ flux. Mechanistically, TIS cells exhibit decreased expression of IP3R isoforms and reduced interaction between type 1 IP3R and VDAC1, impairing Ca²⁺ transfer. This flux is...

Blood-borne factors are essential to maintain neuronal synaptic plasticity and cognitive resilience throughout life. One such factor is osteocalcin (OCN), a hormone produced by osteoblasts that influences multiple physiological processes, including hippocampal neuronal homeostasis. However, the mechanism through which this blood-borne factor communicates with neurons remains unclear. Here we show the importance of a core primary cilium (PC) protein-autophagy axis in mediating the effects of OCN....

CONCLUSIONS: One year of resistance training in well-functioning older adults at retirement age did not influence volume changes in selected brain regions over a 4-year period.

CONCLUSIONS: This eFI identified older adults at increased risk for adverse health outcomes even when data from routine primary care visits were not available. This tool can be integrated into EHRs for frailty assessment at scale.

Chemotherapy-related cognitive impairment, commonly referred to as "chemobrain," significantly affects cancer survivors' quality of life, yet its underlying mechanisms remain unclear. Most chemotherapeutic agents cannot cross the blood-brain barrier (BBB), yet they cause central nervous system side effects, suggesting alternative pathways of toxicity. Given that these drugs interact with the cerebrovascular endothelium at their highest concentrations, it is logical to hypothesize that...

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Accumulation of cerebral senescent cells may compromise the continuum between vascular and neuronal function, leading to damage and cognitive decline. Elimination of senescent cells might therefore preserve vascular and neuronal functions. To test this hypothesis, we used male and female atherosclerotic LDLr^(-/-);hApoB(100)^(+/+) mice (ATX-mice), a model of vascular cognitive impairment (VCI), treated with the senolytic ABT-263 for 3 months (3- to 6-month or 9- to 12-month old). In young male...

In this review, we explore the mechanisms of the blood-cerebrospinal fluid (CSF) barrier and CSF transport. We briefly review the mathematical framework for CSF transport as described by a set of well-studied partial differential equations. Moreover, we describe the major contributors of CSF flow through both diffusive and convective forces beginning at the molecular level and extending into macroscopic clinical observations. In addition, we review neurosurgical perspectives in understanding CSF...

CONCLUSIONS: This portfolio analysis showed an increase in the number of NIH-funded grants focused on cancer survivors and accelerated aging, but notable gaps are evident. Given the rapidly growing survivor population, many of whom will experience accelerated aging trajectories, there is a critical need to better understand accelerated aging phenotypes and mechanisms, so that those at the highest risk for adverse aging-related effects can be identified and interventions developed.

A microglia subpopulation termed "dark microglia" has been associated with aging and neurodegeneration, although its role has remained elusive. New research from Flury et al. in this issue of Neuron shows that dark microglia drive neurodegeneration via secretion of toxic lipids.¹.

INTRODUCTION: One important aspect of walking aid use is transferring safely to the aid from sitting and transferring back to the chair after walking, since these activities have been associated with falls in older adults. Standard frames require their user to push off the chair or ask for help from a carer, which may over time lead to back pain. This study's aim was to assess whether novel handgrips located above the rear feet of a walking frame would facilitate safe transfer as compared to...

Oxidative stress plays a key role in aging and related diseases, including neurodegeneration, cancer, and organ failure. Copper (Cu), a redox-active metal ion, generates reactive oxygen species (ROS), and its dysregulation contributes to aging. Here, we develop activity-based imaging probes for the sensitive detection of Cu(I) and show that labile hepatic Cu activity increases with age, paralleling a decline in ALDH1A1 activity, a protective hepatic enzyme. We also observe an age-related...

Understanding the evolving dynamics of the brain throughout life is pivotal for anticipating and evaluating individual health. While previous research has described age effects on spectral properties of neural signals, it remains unclear which ones are most indicative of age-related processes. This study addresses this gap by analyzing resting-state data obtained from magnetoencephalography (MEG) in 350 adults (18 to 88 y). We employed advanced time-series analysis at the brain region level and...

Longitudinal imaging data are routinely acquired for health studies and patient monitoring. A central goal in longitudinal studies is tracking relevant change over time. Traditional methods remove nuisance variation with custom pipelines to focus on significant changes. In this work, we present a machine learning-based method that automatically ignores irrelevant changes and extracts the time-varying signal of interest. Our method, called Learning-based Inference of Longitudinal imAge Changes...

There is growing evidence that higher intermuscular fat (IMF) is associated with worse processing speed, measured by the digit symbol substitution test (DSST) in older adults. However, the underlying biological mechanisms are not well understood. Considering that both muscle and the brain are metabolically active organs, we sought to identify metabolites that may explain the IMF-DSST association. We assessed 613 plasma metabolites in 2388 participants from the Health, Aging, and Body Composition...

Chemotherapy-induced cognitive impairment (CICI), commonly referred to as "chemobrain," is a frequent and debilitating side effect experienced by cancer survivors treated with paclitaxel (PTX). Preclinical models have shown that PTX promotes cerebromicrovascular endothelial cell senescence, leading to chronic blood-brain barrier (BBB) disruption and neuroinflammation. Conversely, the elimination of senescent cells through senolytic therapies has been shown to restore BBB integrity, reduce...

The increasing number of cancer survivors has brought heightened attention to the side effects of cancer therapies, including chemotherapy-related cognitive impairment (CRCI, commonly referred to as "chemobrain"). Cisplatin and methotrexate, commonly used first-line chemotherapeutics in gynecologic oncology for cancers such as breast, ovarian, and bladder cancer, are clinically associated with long-term cognitive deficits. Building on our previous preclinical studies demonstrating that...

Alzheimer's disease (AD) is predominantly the most recurring and devastating neurological condition among the elderly population, characterized by the accumulation of amyloid-β (Aβ) and phosphorylated tau proteins, and is accompanied by progressive decline of learning and memory. Due to its complex and multifactorial etiology, a wide variety of therapeutic interventions have been developed. Despite constant advancements in the field, effective treatments that ameliorate the severity of...