ArticleNature aging2021
A stress-induced miR-31-CLOCK-ERK pathway is a key driver and therapeutic target for skin aging.
Article in Nature aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Aging of hair follicle stem cells and their niche: mechanisms and regenerative therapeutic strategies.Cell communication and signaling : CCS · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- An updated guide to hair follicle stem cell markers and changes in their expression with aging.JID innovations : skin science from molecules to population health · 2026Review
- Anti-skin aging effects of black ginseng extracts through regulating inflammatory factors and the CLOCK-ERK pathway in mice.Journal of ginseng research · 2026Article
- Rejuvenating senescent hair follicles: a novel conjugated linoleic acid based nanovesicle approach to treat androgenic alopecia.Journal of nanobiotechnology · 2025Article
- Biomarkers of ageing of humans and non-human primates.Nature reviews. Molecular cell biology · 2025Review
- A subset of transposable elements as mechano-response enhancer elements in controlling human embryonic stem cell fate.Nature cell biology · 2025Article
- Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review.Bone research · 2025Review
- MiR-4298 and lncKRTAP5-6-3 regulated Cathepsin D expression through ERK-MAPK signaling pathway in chronic UVB-damaged HaCaT cells.Frontiers in medicine · 2024Article
- Differentially expressed microRNAs in brains of adult females may regulate the maternal block of diapause inCurrent research in insect science · 2024Article
- Overview of the Circadian Clock in the Hair Follicle Cycle.Biomolecules · 2023Review
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- Hair Follicles as a Critical Model for Monitoring the Circadian Clock.International journal of molecular sciences · 2023Review
- Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying.Cell discovery · 2022Article
- The spring-like effect of microRNA-31 in balancing inflammatory and regenerative responses in colitis.Frontiers in microbiology · 2022Article
- Toward Elucidating Epigenetic and Metabolic Regulation of Stem Cell Lineage Plasticity in Skin Aging.Frontiers in cell and developmental biology · 2022Review
- Review
- The circadian clock and diseases of the skin.FEBS letters · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regressive changes in epithelial stem cells underlie mammalian skin aging, but the driving mechanisms are not well understood. Here, we report that mouse skin hair follicle stem cell (HFSC) aging is initiated by their intrinsic upregulation of miR-31, a microRNA that can be induced by physical injury or genotoxic stress and is also strongly upregulated in aged human skin epithelium. Using transgenic and conditional knockout mouse models plus a lineage-tracing technique, we show that miR-31 acts as a key driver of HFSC aging by directly targeting Clock, a core circadian clock gene whose deregulation activates a MAPK/ERK cascade to induce HFSC depletion via transepidermal elimination. Notably, blocking this pathway by either conditional miR-31 ablation or clinically approved MAPK/ERK inhibitors provides safe and effective protection against skin aging, enlightening a promising therapeutic avenue for treating skin aging and other genotoxic stress-induced skin conditions such as radiodermatitis.
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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.