Academic Journal
[Systemic Reprogramming of Cellular Senescence: Coordinated Regulation of Metabolism, Epigenetics, and Proteostasis].
| Τίτλος: | [Systemic Reprogramming of Cellular Senescence: Coordinated Regulation of Metabolism, Epigenetics, and Proteostasis]. |
|---|---|
| Μεταγλωττισμένος Τίτλος: | 细胞衰老的系统性重编程：代谢、表观遗传与蛋白稳态的协同调控. |
| Συγγραφείς: | Zheng Y; •（） （ 610072）Department of Geriatric Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (Affiliated Hospital of University of Electronic Science and Technology of China), Chengdu 610072, China., Liu Q; •（） （ 610072）Department of Geriatric Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (Affiliated Hospital of University of Electronic Science and Technology of China), Chengdu 610072, China., Wang R; •（） （ 610072）Department of Geriatric Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (Affiliated Hospital of University of Electronic Science and Technology of China), Chengdu 610072, China., Sun C; •（） （ 610072）Department of Geriatric Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (Affiliated Hospital of University of Electronic Science and Technology of China), Chengdu 610072, China. |
| Πηγή: | Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition [Sichuan Da Xue Xue Bao Yi Xue Ban] 2026 Jul 20; Vol. 57 (4), pp. 915-924. |
| Τύπος έκδοσης: | Journal Article; Review; English Abstract |
| Γλώσσα: | Chinese |
| Στοιχεία περιοδικού: | Publisher: Sichuan da xue xue bao (yi xue ban) bian ji bu Country of Publication: China NLM ID: 101162609 Publication Model: Print Cited Medium: Print ISSN: 1672-173X (Print) Linking ISSN: 1672173X NLM ISO Abbreviation: Sichuan Da Xue Xue Bao Yi Xue Ban Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chengdu Shi : Sichuan da xue xue bao (yi xue ban) bian ji bu, 2003- |
| Ιατρικοί όροι (MeSH): | Cellular Senescence*/genetics , Cellular Senescence*/physiology , Proteostasis*/genetics , Cellular Reprogramming*/genetics , Epigenesis, Genetic*, NAD/metabolism ; Humans ; Kruppel-Like Factor 4 ; Metabolic Reprogramming ; Animals |
| Περίληψη: | Cellular senescence has long been considered an irreversible process. However, recent breakthroughs in partial cellular reprogramming have demonstrated that senescent cells maintain a metastable state amenable to resetting. This review outlines a systemic framework for anti-aging interventions that integrate three core dimensions. First, metabolic reprogramming through the elevation of nicotinamide adenine dinucleotide (NAD+) levels provides the energetic and coenzymatic foundation necessary for a systemic reset. Second, spatiotemporally controlled epigenetic resetting, mediated by Oct4-Sox2-Klf4-c-Myc (OSKM) factors or small molecules, restores youthful transcriptional programs without compromising cellular identity. Third, the restoration of proteostasis via the autophagy-lysosome and ubiquitin-proteasome systems serves as the critical execution mechanism that eliminates damaged biomaterials and ensures the proper folding of newly synthesized proteins. Despite these advances, the research field still faces major challenges, including the lack of a clearly defined therapeutic window for safe reprogramming, limited efficiency of tissue-specific delivery, and insufficient evidence regarding the long-term safety of therapeutic interventions. Future studies should focus on integrating single-cell omics, DNA methylation clocks, and artificial intelligence-assisted analyses to establish precision-based evaluation metrics for evaluating cellular rejuvenation. In addition, the development of next-generation delivery platforms, including lipid nanoparticles (LNPs) and engineered exosomes, will facilitate precision-based regulation of multi-level synergistic interventions. Ultimately, anti-aging medicine is evolving from single-pathway interventions toward a comprehensive paradigm of systemic reprogramming driven by the multi-axial synergy of metabolism, epigenetics, and proteostasis. (© 2026《四川大学学报（医学版）》编辑部 Copyright © 2026 Editorial Office of Journal of Sichuan University (Medical Sciences).) |
| Competing Interests: | 所有作者均声明不存在利益冲突 |
| References: | Cell Metab. 2016 Jun 14;23(6):1127-1139. (PMID: 27304511) Nature. 2020 Dec;588(7836):124-129. (PMID: 33268865) Curr Opin Genet Dev. 2024 Dec;89:102226. (PMID: 39586652) Nat Cell Biol. 2017 Nov;19(11):1298-1306. (PMID: 29058720) Aging Cell. 2022 Apr;21(4):e13589. (PMID: 35263032) EMBO Mol Med. 2021 Jul 7;13(7):e13943. (PMID: 34041853) Annu Rev Biochem. 2015;84:435-64. (PMID: 25784053) Nat Aging. 2025 Jul;5(7):1249-1265. (PMID: 40437307) Cell Stem Cell. 2014 May 1;14(5):606-16. (PMID: 24630793) Cell. 2013 Jul 18;154(2):430-41. (PMID: 23870130) Science. 2021 Jun 11;372(6547):1224-1229. (PMID: 33888596) Cell Stem Cell. 2015 Jun 4;16(6):613-25. (PMID: 26046761) Nat Commun. 2020 Mar 24;11(1):1545. (PMID: 32210226) PLoS One. 2010 Apr 01;5(4):e9979. (PMID: 20376313) Crit Rev Eukaryot Gene Expr. 2015;25(1):59-75. (PMID: 25955819) Cell. 2023 Jan 19;186(2):243-278. (PMID: 36599349) Aging (Albany NY). 2023 Jul 12;15(13):5966-5989. (PMID: 37437248) Nat Med. 2015 Dec;21(12):1406-15. (PMID: 26646497) Cell Metab. 2016 Dec 13;24(6):795-806. (PMID: 28068222) Antioxid Redox Signal. 2011 Apr 15;14(8):1551-85. (PMID: 20812785) Expert Opin Drug Metab Toxicol. 2017 Mar;13(3):323-330. (PMID: 27766890) Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 May 20;55(3):783-792. (PMID: 38948289) Nat Aging. 2023 Sep;3(9):1144-1166. (PMID: 37563227) NPJ Aging. 2022 May 1;8(1):5. (PMID: 35927255) Curr Nutr Rep. 2023 Sep;12(3):445-464. (PMID: 37273100) Semin Hematol. 2012 Oct;49(4):330-41. (PMID: 23079063) Nat Chem Biol. 2025 May;21(5):635-647. (PMID: 40251434) Nat Rev Mol Cell Biol. 2019 Jul;20(7):421-435. (PMID: 30733602) Nat Aging. 2023 Jun;3(6):642-660. (PMID: 37142830) Cell Rep Med. 2022 May 17;3(5):100633. (PMID: 35584623) Sci Immunol. 2017 Feb;2(8):. (PMID: 28439570) Genes Dev. 2012 Jun 15;26(12):1326-38. (PMID: 22677546) Nat Aging. 2022 Mar;2(3):243-253. (PMID: 37118377) Signal Transduct Target Ther. 2022 Nov 7;7(1):374. (PMID: 36336680) Acta Pharmacol Sin. 2023 Jan;44(1):92-104. (PMID: 35794374) Nat Rev Drug Discov. 2012 Jun 01;11(6):443-61. (PMID: 22653216) Nat Rev Immunol. 2018 Sep;18(9):543. (PMID: 30082757) iScience. 2020 Dec 07;24(1):101902. (PMID: 33385109) Nat Metab. 2020 Nov;2(11):1284-1304. (PMID: 33199925) Nat Med. 2016 Dec;22(12):1428-1438. (PMID: 27841876) Nat Chem Biol. 2025 Nov;21(11):1675-1687. (PMID: 40419771) Nat Metab. 2020 Nov;2(11):1265-1283. (PMID: 33199924) Nat Aging. 2021 Aug;1(8):634-650. (PMID: 34901876) NPJ Metab Health Dis. 2025 Jun 18;3(1):26. (PMID: 40604314) Sci Rep. 2019 Feb 28;9(1):3170. (PMID: 30816680) Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141. (PMID: 33353981) Aging (Albany NY). 2023 Jun 13;15(11):4685-4698. (PMID: 37315291) Geroscience. 2020 Apr;42(2):527-546. (PMID: 32056076) Nat Commun. 2021 Sep 6;12(1):5305. (PMID: 34489447) Free Radic Biol Med. 2014 Feb;67:304-13. (PMID: 24291399) |
| Contributed Indexing: | Keywords: Aging; Cellular reprogramming; Epigenetics; Nicotinamide adenine dinucleotide; Proteostasis |
| Substance Nomenclature: | 0 (Kruppel-Like Factor 4) 0 (KLF4 protein, human) 0U46U6E8UK (NAD) |
| Entry Date(s): | Date Created: 20260903 Date Completed: 20260903 Latest Revision: 20260904 |
| Update Code: | 20260904 |
| PubMed Central ID: | PMC13534517 |
| DOI: | 10.12182/20260760105 |
| PMID: | 42688282 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1672-173X |
|---|---|
| DOI: | 10.12182/20260760105 |