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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.

The cGAS-STING pathway mediates innate immune responses to cytosolic DNA. In addition to its well-established role in inducing inflammatory cytokines, activation of the cGAS-STING pathway also induces noncanonical autophagy, a process involving the conjugation of the ATG8 family of ubiquitin-like proteins to membranes of the endolysosomal system. The mechanisms and functions of STING-induced autophagy remain poorly understood. In this study, we demonstrated that STING activation induced...

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...

No abstract

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.

Rodent and monkey facilities imperiled by Trump plan to cut overhead payments