ArticleMolecular systems biology2024
Derailed protein turnover in the aging mammalian brain.
Article in Molecular systems biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Local autophagy impairment triggers brain-wide presynaptic remodeling and resilience.The EMBO journal · 2026Article
- Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains.Nature communications · 2026Article
- Levetiracetam prevents Aβ production through SV2a-dependent modulation of APP processing in Alzheimer's disease models.Science translational medicine · 2026Article
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- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- Microglia in Brain Aging and Age-Related Diseases: Friends or Foes?International journal of molecular sciences · 2025Review
- Genetic and proteomic analysis identifies BAG3 as an amyloid-responsive regulator of neuronal proteostasis.Acta neuropathologica · 2025Article
- Proteins with cognition-associated structural changes in a rat model of aging exhibit reduced refolding capacity.Science advances · 2025Article
- Synaptic proteins that aggregate and degrade slower with aging accumulate in microglia.bioRxiv : the preprint server for biology · 2025Article
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- A novel, rapidly progressive ataxia due to a spontaneous Myo5a mutation in mice impairs transport proteins and alters mitochondria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Review
- Oxidative Stress and the Central Nervous System.Antioxidants (Basel, Switzerland) · 2025Article
- The ALS-associated co-chaperone DNAJC7 mediates neuroprotection against proteotoxic stress by modulating HSF1 activity.bioRxiv : the preprint server for biology · 2024Article
- An Extensive Atlas of Proteome and Phosphoproteome Turnover Across Mouse Tissues and Brain Regions.bioRxiv : the preprint server for biology · 2024Article
- Sex as a biological variable in ageing: insights and perspectives on the molecular and cellular hallmarks.Open biology · 2024Review
- The Ubiquitin Tale: Current Strategies and Future Challenges.ACS pharmacology & translational science · 2024Review
- Long-lived proteins and DNA as candidate predictive biomarkers for tissue associated diseases.iScience · 2024Article
- Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain.Nucleic acids research · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Efficient protein turnover is essential for cellular homeostasis and organ function. Loss of proteostasis is a hallmark of aging culminating in severe dysfunction of protein turnover. To investigate protein turnover dynamics as a function of age, we performed continuous in vivo metabolic stable isotope labeling in mice along the aging continuum. First, we discovered that the brain proteome uniquely undergoes dynamic turnover fluctuations during aging compared to heart and liver tissue. Second, trends in protein turnover in the brain proteome during aging showed sex-specific differences that were tightly tied to cellular compartments. Next, parallel analyses of the insoluble proteome revealed that several cellular compartments experience hampered turnover, in part due to misfolding. Finally, we found that age-associated fluctuations in proteasome activity were associated with the turnover of core proteolytic subunits, which was recapitulated by pharmacological suppression of proteasome activity. Taken together, our study provides a proteome-wide atlas of protein turnover across the aging continuum and reveals a link between the turnover of individual proteasome subunits and the age-associated decline in proteasome activity.
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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.