ArticleProceedings of the National Academy of Sciences of the United States of America2020
Cellular proteostasis decline in human senescence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Innovations in Skin and Soft Tissue Aging-A Systematic Literature Review and Market Analysis of Therapeutics and Associated Outcomes.Aesthetic plastic surgery · 2023Pooled it
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- More than the 'master regulator of cytosolic proteostasis': new roles for HSF1 in promoting tissue health.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Salvianolic Acid a Disrupts the HSP90α-AKT-PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.The EMBO journal · 2026Article
- Immunohistological detection of pentosidine in the epiglottis:A contribution to molecular age estimation.International journal of legal medicine · 2026Article
- Proteostasis decline and endoplasmic reticulum stress in aging: Implications for cellular senescence and senescence-associated secretory phenotype regulation.Neural regeneration research · 2026Article
- Effects of micro- and nano-plastics exposure on cellular senescence: an overview.Archives of toxicology · 2026Review
- Synphilin-1 mitigates autophagy dysfusnction, modulates ubiquitinated protein aggregation, and promotes cell survival during proteotoxic stress.bioRxiv : the preprint server for biology · 2026Article
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Review
- Comprehensive profiling of circRNAs reveals stimulus-specific networks and core regulators of cellular senescence.PloS one · 2026Article
- Characterization of the Intact Proteomic Profile of Senescent-Associated Secretory Phenotype by Top-Down Mass Spectrometry.Analytical chemistry · 2025Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- In vivo modeling of lethal congenital contracture syndrome 1 suggests pathomechanisms in cellular stress responses.The FEBS journal · 2025Article
- Biomarkers of ageing of humans and non-human primates.Nature reviews. Molecular cell biology · 2025Review
- Lymphoma accelerates T cell and tissue aging.Cancer cell · 2025Article
- Thermogenic Adipose ADH5 Counteracts Age-related Metabolic Decline.bioRxiv : the preprint server for biology · 2025Article
- Immunoproteasome remodeling in senescing human macrophages reveals the loss of PA28αβ capping as a hallmark of immunosenescence.Communications biology · 2025Article
- Oxidative Stress-Driven Cellular Senescence: Mechanistic Crosstalk and Therapeutic Horizons.Antioxidants (Basel, Switzerland) · 2025Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteostasis collapse, the diminished ability to maintain protein homeostasis, has been established as a hallmark of nematode aging. However, whether proteostasis collapse occurs in humans has remained unclear. Here, we demonstrate that proteostasis decline is intrinsic to human senescence. Using transcriptome-wide characterization of gene expression, splicing, and translation, we found a significant deterioration in the transcriptional activation of the heat shock response in stressed senescent cells. Furthermore, phosphorylated HSF1 nuclear localization and distribution were impaired in senescence. Interestingly, alternative splicing regulation was also dampened. Surprisingly, we found a decoupling between different unfolded protein response (UPR) branches in stressed senescent cells. While young cells initiated UPR-related translational and transcriptional regulatory responses, senescent cells showed enhanced translational regulation and endoplasmic reticulum (ER) stress sensing; however, they were unable to trigger UPR-related transcriptional responses. This was accompanied by diminished ATF6 nuclear localization in stressed senescent cells. Finally, we found that proteasome function was impaired following heat stress in senescent cells, and did not recover upon return to normal temperature. Together, our data unraveled a deterioration in the ability to mount dynamic stress transcriptional programs upon human senescence with broad implications on proteostasis control and connected proteostasis decline to human aging.
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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.