ReviewAging cell2022
Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.
Review in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural Analysis of Human LonP1 Protease Bound with the Native Substrate.Life (Basel, Switzerland) · 2026Article
- UBE3A-mediated mH2A1 Ubiquitination activates TERT transcription to promote senescence resistance in pancreatic cancer.Cell death & disease · 2026Article
- Investigating the Ligand-Binding Properties of N-arylbenzimidazoles as Novel Elastase Inhibitors.ChemMedChem · 2026Article
- Review
- Mechanobiology of hippocampal neurogenesis: directing neural stem cell fate through physical cues.Frontiers in molecular neuroscience · 2026Review
- Perturbation of multiprotein complexes in skeletal muscle induces protective proteases in the CNS that degrade pathogenic proteins.npj aging · 2025Article
- Transcriptomic insights into the healthspan-enhancing effects of C. chinensis seed and E. ulmoides bark extracts in Caenorhabditis elegans.Biogerontology · 2025Article
- Data Processing and Analysis in Positional Proteomics.Proteomics · 2025Review
- Employing complementary fractionation-based N-terminomics approaches enhances the identification of legumain cleavage events in naïve and inflamed colon tissue.Protein science : a publication of the Protein Society · 2025Article
- Genome-wide molecular characterization and expression profiling of the cysteine protease gene family in maize.BMC genomics · 2025Article
- Genome-wide association studies of Alzheimer's disease and related disorders stratified by sex, onset age, and Apolipoprotein E genotype reveal novel risk loci in African Americans.Alzheimer's research & therapy · 2025Article
- PERRC: Protease Engineering with Reactant Residence Time Control.ACS synthetic biology · 2025Article
- Preventing MSC aging and enhancing immunomodulation: Novel strategies for cell-based therapies.Regenerative therapy · 2025Review
- Review
- Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.Aging and disease · 2025Review
- Activatable Photosensitizers: From Fundamental Principles to Advanced Designs.Angewandte Chemie (International ed. in English) · 2025Review
- Mesenchymal stem cells derived exosomes: a new era in cardiac regeneration.Stem cell research & therapy · 2025Review
- The aggregate proteome ofFrontiers in aging neuroscience · 2025Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein quality control ensures the degradation of damaged and misfolded proteins. Derangement of proteostasis is a primary cause of aging and age-associated diseases. The ubiquitin-proteasome and autophagy-lysosome play key roles in proteostasis but, in addition to these systems, the human genome encodes for ~600 proteases, also known as peptidases. Here, we examine the role of proteases in aging and age-related neurodegeneration. Proteases are present across cell compartments, including the extracellular space, and their substrates encompass cellular constituents, proteins with signaling functions, and misfolded proteins. Proteolytic processing by proteases can lead to changes in the activity and localization of substrates or to their degradation. Proteases cooperate with the autophagy-lysosome and ubiquitin-proteasome systems but also have independent proteolytic roles that impact all hallmarks of cellular aging. Specifically, proteases regulate mitochondrial function, DNA damage repair, cellular senescence, nutrient sensing, stem cell properties and regeneration, protein quality control and stress responses, and intercellular signaling. The capacity of proteases to regulate cellular functions translates into important roles in preserving tissue homeostasis during aging. Consequently, proteases influence the onset and progression of age-related pathologies and are important determinants of health span. Specifically, we examine how certain proteases promote the progression of Alzheimer's, Huntington's, and/or Parkinson's disease whereas other proteases protect from neurodegeneration. Mechanistically, cleavage by proteases can lead to the degradation of a pathogenic protein and hence impede disease pathogenesis. Alternatively, proteases can generate substrate byproducts with increased toxicity, which promote disease progression. Altogether, these studies indicate the importance of proteases in aging and age-related neurodegeneration.
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Registered trials
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.