ArticleScience advances2022
Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 69 citations in OpenAlex.
- Comparative analysis of neuronal proteolytic pathways reveals neuron-specific and sub-compartmental-specific capacities with aging.Cellular and molecular life sciences : CMLS · 2026Article
- Analysis in vivo using a new method, ARGO (Analysis of Red-Green Offset), reveals complexity and cell-type specificity in presynaptic turnover of synaptic vesicle protein Synaptogyrin/SNG-1.Molecular biology of the cell · 2026Article
- MicroRNA-29 acutely regulates memory stability, expression of synaptic genes, and DNA methylation in the mouse adult hippocampus.Cellular and molecular life sciences : CMLS · 2026Article
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- Molecular Mechanisms and Therapeutic Potential of Degron-Mediated Proteostasis Regulation in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2026Review
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- A Critical Assessment of Fasting to Promote Metabolic Health and Longevity.Endocrine reviews · 2025Review
- Age-related decline in protein turnover highlights cystatin C dysfunction and links proteostasis collapse to neuroinflammation in the murine cortex.Biogerontology · 2025Article
- AnalysisbioRxiv : the preprint server for biology · 2025Article
- Altered translation elongation contributes to key hallmarks of aging in the killifish brain.Science (New York, N.Y.) · 2025Article
- Deuterium labeling enables proteome-wide turnover kinetics analysis in cell culture.Cell reports methods · 2025Article
- Proteins with cognition-associated structural changes in a rat model of aging exhibit reduced refolding capacity.Science advances · 2025Article
- Loss of Pol III repressor Maf1 in neurons promotes longevity by preventing the age-related decline in 5S rRNA and translation.PLoS biology · 2025Article
- Aging and diet alter the protein ubiquitylation landscape in the mouse brain.Nature communications · 2025Article
- A robust multiplex-DIA workflow profiles protein turnover regulations associated with cisplatin resistance and aneuploidy.Nature communications · 2025Article
- Synaptic proteins that aggregate and degrade slower with aging accumulate in microglia.bioRxiv : the preprint server for biology · 2025Article
- APOE genotype determines cell-type-specific pathological landscape of Alzheimer's disease.Neuron · 2025Article
- Article
- Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging.Nature aging · 2025Article
- Determination of Trends Underlying Aspartic Acid Isomerization in Intact Proteins Reveals Unusually Rapid Isomerization of Tau.ACS chemical neuroscience · 2025Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is a prominent risk factor for neurodegenerative disorders (NDDs); however, the molecular mechanisms rendering the aged brain particularly susceptible to neurodegeneration remain unclear. Here, we aim to determine the link between physiological aging and NDDs by exploring protein turnover using metabolic labeling and quantitative pulse-SILAC proteomics. By comparing protein lifetimes between physiologically aged and young adult mice, we found that in aged brains protein lifetimes are increased by ~20% and that aging affects distinct pathways linked to NDDs. Specifically, a set of neuroprotective proteins are longer-lived in aged brains, while some mitochondrial proteins linked to neurodegeneration are shorter-lived. Strikingly, we observed a previously unknown alteration in proteostasis that correlates to parsimonious turnover of proteins with high biosynthetic costs, revealing an overall metabolic adaptation that preludes neurodegeneration. Our findings suggest that future therapeutic paradigms, aimed at addressing these metabolic adaptations, might be able to delay NDD onset.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.