skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on November 3, 2026

Title: Slowing down to take it in: Endocytosis during cellular aging
Aging cells functionally decline and accumulate damage through poorly understood mechanisms. In this issue, Antentor et al. (https://doi.org/10.1083/jcb.202412064) find that increased vacuolar pH in older yeast cells slows clathrin-mediated endocytosis. These findings have broad implications in aging-related plasma membrane protein quality control.  more » « less
Award ID(s):
1942395
PAR ID:
10656640
Author(s) / Creator(s):
Publisher / Repository:
Rockefeller University Press
Date Published:
Journal Name:
Journal of Cell Biology
Volume:
224
Issue:
11
ISSN:
0021-9525
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Smith, Amber M (Ed.)
    Understanding the mechanisms of the cellular aging processes is crucial for attempting to extend organismal lifespan and for studying age-related degenerative diseases. Yeast cells divide through budding, providing a classical biological model for studying cellular aging. With their powerful genetics, relatively short cell cycle, and well-established signaling pathways also found in animals, yeast cells offer valuable insights into the aging process. Recent experiments suggested the existence of two aging modes in yeast characterized by nucleolar and mitochondrial declines, respectively. By analyzing experimental data, this study shows that cells evolving into those two aging modes behave differently when they are young. While buds grow linearly in both modes, cells that consistently generate spherical buds throughout their lifespan demonstrate greater efficacy in controlling bud size and growth rate at young ages. A three-dimensional multiscale chemical-mechanical model was developed and used to suggest and test hypothesized impacts of aging on bud morphogenesis. Experimentally calibrated model simulations showed that during the early stage of budding, tubular bud shape in one aging mode could be generated by locally inserting new materials at the bud tip, a process guided by the polarized Cdc42 signal. Furthermore, the aspect ratio of the tubular bud could be stabilized during the late stage as observed in experiments in this work. The model simulation results suggest that the localization of new cell surface material insertion, regulated by chemical signal polarization, could be weakened due to cellular aging in yeast and other cell types, leading to the change and stabilization of the bud aspect ratio. 
    more » « less
  2. Brain age (BA), distinct from chronological age (CA), can be estimated from MRIs to evaluate neuroanatomic aging in cognitively normal (CN) individuals. BA, however, is a cross-sectional measure that summarizes cumulative neuroanatomic aging since birth. Thus, it conveys poorly recent or contemporaneous aging trends, which can be better quantified by the (temporal) pace P of brain aging. Many approaches to map P, however, rely on quantifying DNA methylation in whole-blood cells, which the blood–brain barrier separates from neural brain cells. We introduce a three-dimensional convolutional neural network (3D-CNN) to estimate P noninvasively from longitudinal MRI. Our longitudinal model (LM) is trained on MRIs from 2,055 CN adults, validated in 1,304 CN adults, and further applied to an independent cohort of 104 CN adults and 140 patients with Alzheimer’s disease (AD). In its test set, the LM computes P with a mean absolute error (MAE) of 0.16 y (7% mean error). This significantly outperforms the most accurate cross-sectional model, whose MAE of 1.85 y has 83% error. By synergizing the LM with an interpretable CNN saliency approach, we map anatomic variations in regional brain aging rates that differ according to sex, decade of life, and neurocognitive status. LM estimates of P are significantly associated with changes in cognitive functioning across domains. This underscores the LM’s ability to estimate P in a way that captures the relationship between neuroanatomic and neurocognitive aging. This research complements existing strategies for AD risk assessment that estimate individuals’ rates of adverse cognitive change with age. 
    more » « less
  3. Understanding the behavior of pressure increases in lithium-ion (Li-ion) cells is essential for prolonging the lifespan of Li-ion battery cells and minimizing the safety risks associated with cell aging. This work investigates the effects of C-rates and temperature on pressure behavior in commercial lithium cobalt oxide (LCO)/graphite pouch cells. The battery is volumetrically constrained, and the mechanical pressure response is measured using a force gauge as the battery is cycled. The effect of the C-rate (1C, 2C, and 3C) and ambient temperature (10 °C, 25 °C, and 40 °C) on the increase in battery pressure is investigated. By analyzing the change in the minimum, maximum, and pressure difference per cycle, we identify and discuss the effects of different factors (i.e., SEI layer damage, electrolyte decomposition, lithium plating) on the pressure behavior. Operating at high C-rates or low temperatures rapidly increases the residual pressure as the battery is cycled. The results suggest that lithium plating is predominantly responsible for battery expansion and pressure increase during the cycle aging of Li-ion cells rather than electrolyte decomposition. Electrochemical impedance spectroscopy (EIS) measurements can support our conclusions. Postmortem analysis of the aged cells was performed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) to confirm the occurrence of lithium plating and film growth on the anodes of the aged cells. This study demonstrates that pressure measurements can provide insights into the aging mechanisms of Li-ion batteries and can be used as a reliable predictor of battery degradation. 
    more » « less
  4. The cells in dynamic random access memory (DRAM) degrade over time as a result of aging, leading to poor performance and potential security vulnerabilities. With a globalized horizontal supply chain, aged counterfeit DRAMs could end up on the market, posing a significant threat if employed in critical infrastructure. In this work, we look at the retention behavior of commercial DRAM chips from real-time silicon measurements and investigate how the reliability of DRAM cells degrade with accelerated aging. We analyze the retention-based errors at three different aging points to observe the design-induced variations, analyze the pattern dependency, and explore the impacts of accelerated aging for multiple DRAM vendors. We also investigate the DRAM chips’ statistical distribution to attribute the vital wear-out effects present in DRAM. We see a continuous increase in retention error as DRAM chips age and therefore infer that the aged retention signatures can be used to differentiate recycled DRAM chips in the supply chain. We also discuss the roles of device signature in DRAM aging and aging-related security implication on DRAM row-hammer error. 
    more » « less
  5. Abstract Studies in multiple organisms have shown that aging is accompanied by several molecular phenotypes that include dysregulation of chromatin. Since chromatin regulates DNA-based processes such as transcription, alterations in chromatin modifications could impact the transcriptome and function of aging cells. In flies, as in mammals, the aging eye undergoes changes in gene expression that correlate with declining visual function and increased risk of retinal degeneration. However, the causes of these transcriptome changes are poorly understood. Here, we profiled chromatin marks associated with active transcription in the agingDrosophilaeye to understand how chromatin modulates transcriptional outputs. We found that both H3K4me3 and H3K36me3 globally decrease across all actively expressed genes with age. However, we found no correlation with changes in differential gene expression. Downregulation of the H3K36me3 methyltransferase Set2 in young photoreceptors revealed significant changes in splicing events that overlapped significantly with those observed in aging photoreceptors. These overlapping splicing events impacted multiple genes involved in phototransduction and neuronal function. Since proper splicing is essential for visual behavior, and because agingDrosophilaundergo a decrease in visual function, our data suggest that H3K36me3 could play a role in maintaining visual function in the aging eye through regulating alternative splicing. 
    more » « less