Academic Journal
Photo-downregulation of SIRT4 mitigates aging in mice by enhancing H3K9ac via fatty acid metabolism.
| Τίτλος: | Photo-downregulation of SIRT4 mitigates aging in mice by enhancing H3K9ac via fatty acid metabolism. |
|---|---|
| Συγγραφείς: | Deng F; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Yang R; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Niu J; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Wang M; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Liu Y; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Li X; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Gao Z; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Yang L; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Liu H; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China., Yang Y; The First Affiliated Hospital of Xi'an Medical University, Xi'an, China., Yu Z; The First Affiliated Hospital of Xi'an Medical University, Xi'an, China., Zhang L; School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, China. |
| Πηγή: | ELife [Elife] 2026 Oct 08; Vol. 15. Date of Electronic Publication: 2026 Oct 08. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
| Ιατρικοί όροι (MeSH): | Fatty Acids*/metabolism , Sirtuins*/metabolism , Sirtuins*/genetics , Aging*/radiation effects , Histones*/metabolism , Mitochondrial Proteins*/metabolism , Mitochondrial Proteins*/genetics, Keratinocytes/metabolism ; Keratinocytes/radiation effects ; Acetylation/radiation effects ; Down-Regulation/radiation effects ; Cellular Senescence/radiation effects ; Mitochondria/metabolism ; Sirtuin 1/metabolism ; Gene Expression Regulation/radiation effects ; Animals ; Mice ; Red Light |
| Περίληψη: | As organisms age, mitochondrial metabolic activity declines, and disrupted gene expression regulation mediated by histone acetylation induces the emergence of senescent physiological phenotypes in tissues. In this study, we found that periodic exposure to red light significantly increased histone H3 Lys9 acetylation (H3K9ac) levels in the tissues and organs of aged mice. Following red light exposure, silent information regulation factor 4 (SIRT4) protein levels in keratinocytes were notably reduced, whereas glycolysis, fatty acid metabolism, and the tricarboxylic acid (TCA) cycle were significantly activated in keratinocytes. The reduction in mitochondrial SIRT4 levels enhances the acetylation of mitochondrial metabolic proteins, particularly malonyl-CoA decarboxylase, a potent inhibitor of the key rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A) in fatty acid oxidation. This process promotes mitochondrial fatty acid oxidation and the TCA cycle. Additionally, the decrease in SIRT4 activates SIRT1 through feedback mechanisms, thereby alleviating its inhibition on PPAR-α in senescent keratinocytes and comprehensively activating the expression of genes related to lipid metabolism. This lipid metabolism activation ultimately facilitates the accumulation of acetyl-CoA within keratinocytes, increases H3K9ac levels, and reshapes the expression patterns of senescence-related genes. Eventually, cellular aging is effectively mitigated by the synergistic regulation of metabolism, inflammation, and gene expression. (© 2026, Deng et al.) |
| Competing Interests: | FD, RY, JN, MW, YL, XL, ZG, LY, HL, YY, ZY, LZ No competing interests declared |
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| Grant Information: | 31971315 National Natural Science Foundation of China; 2024M754229 China Postdoctoral Science Foundation |
| Contributed Indexing: | Keywords: H3K9ac; SIRT4; cell biology; fatty acid metabolism; mouse; red light; skin aging |
| Substance Nomenclature: | 0 (Fatty Acids) EC 3.5.1.- (Sirtuins) EC 3.5.1.- (SIRT4 protein, mouse) 0 (Histones) 0 (Mitochondrial Proteins) EC 3.5.1.- (Sirtuin 1) EC 3.5.1.- (Sirt1 protein, mouse) |
| Entry Date(s): | Date Created: 20261008 Date Completed: 20261008 Latest Revision: 20261010 |
| Update Code: | 20261010 |
| PubMed Central ID: | PMC13649259 |
| DOI: | 10.7554/eLife.111498 |
| PMID: | 42847170 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2050-084X |
|---|---|
| DOI: | 10.7554/eLife.111498 |