دورية أكاديمية
أعرض في EDS

Cell-type specific impact of metformin on monocyte epigenetic age reversal in virally suppressed older people living with HIV.

التفاصيل البيبلوغرافية
العنوان: Cell-type specific impact of metformin on monocyte epigenetic age reversal in virally suppressed older people living with HIV.
المؤلفون: Corley MJ; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, New York, USA., Pang APS; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, New York, USA., Shikuma CM; Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA., Ndhlovu LC; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, New York, USA.
المصدر: Aging cell [Aging Cell] 2024 Jan; Vol. 23 (1), pp. e13926. Date of Electronic Publication: 2023 Sep 07.
نوع المنشور: Randomized Controlled Trial; Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Pub., c2002-
مواضيع طبية MeSH: Metformin*/pharmacology , Metformin*/therapeutic use , HIV Infections*/drug therapy , HIV Infections*/genetics, Humans ; Aged ; Monocytes ; CD8-Positive T-Lymphocytes ; Retrospective Studies ; Biomarkers ; Epigenesis, Genetic ; DNA Methylation
مستخلص: The anti-diabetic drug metformin may promote healthy aging. However, few clinical trials of metformin assessing biomarkers of aging have been completed. In this communication, we retrospectively examined the effect of metformin on epigenetic age using principal component (PC)-based epigenetic clocks, mitotic clocks, and pace of aging in peripheral monocytes and CD8 + T cells from participants in two clinical trials of virologically-suppressed people living with HIV (PLWH) with normal glucose receiving metformin. In a small 24-week clinical trial that randomized participants to receive either adjunctive metformin or observation, we observed significantly decreased PCPhenoAge and PCGrimAge estimates of monocytes from only participants in the metformin arm by a mean decrease of 3.53 and 1.84 years from baseline to Week 24. In contrast, we observed no significant differences in all PC clocks for participants in the observation arm over 24 weeks. Notably, our analysis of epigenetic mitotic clocks revealed significant increases for monocytes in the metformin arm when comparing baseline to Week 24, suggesting an impact of metformin on myeloid cell kinetics. Analysis of a single-arm clinical trial of adjunctive metformin in eight PLWH revealed no significant differences across all epigenetic clocks assessed in CD8 + T cells at 4- and 8-week time points. Our results suggest cell-type-specific myeloid effects of metformin captured by PC-based epigenetic clock biomarkers. Larger clinical studies of metformin are needed to validate these observations and this report highlights the need for further inclusion of PLWH in geroscience trials evaluating the effect of metformin on increasing healthspan and lifespan.
(© 2023 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
References: Patterns (N Y). 2020 May 8;1(2):. (PMID: 32885222)
Genome Biol. 2016 Oct 3;17(1):205. (PMID: 27716309)
J Acquir Immune Defic Syndr. 2012 Jul 1;60 Suppl 1:S1-18. (PMID: 22688010)
Neurology. 2017 Apr 4;88(14):1349-1357. (PMID: 28258081)
Mol Cell. 2016 Apr 21;62(2):157-168. (PMID: 27105112)
Aging Cell. 2024 Jan;23(1):e13926. (PMID: 37675817)
Aging Cell. 2019 Dec;18(6):e13028. (PMID: 31496122)
Aging (Albany NY). 2017 Feb 14;9(2):419-446. (PMID: 28198702)
AIDS Res Hum Retroviruses. 2020 Apr;36(4):303-305. (PMID: 31731885)
AIDS. 2018 Jul 17;32(11):1465-1474. (PMID: 29746298)
BMC Bioinformatics. 2014 Sep 19;15:312. (PMID: 25239148)
Immunol Lett. 2021 Feb;230:1-10. (PMID: 33309673)
Cell Metab. 2016 Jun 14;23(6):1060-1065. (PMID: 27304507)
Front Genet. 2022 Sep 26;13:955835. (PMID: 36226195)
J Infect Dis. 2015 Nov 15;212(10):1563-73. (PMID: 25969563)
Trends Endocrinol Metab. 2019 Oct;30(10):745-755. (PMID: 31405774)
Genome Med. 2020 Jun 24;12(1):56. (PMID: 32580750)
Clin Infect Dis. 2009 Dec 1;49(11):1756-62. (PMID: 19886793)
Cell Stem Cell. 2013 Apr 4;12(4):413-25. (PMID: 23415915)
J Immunol. 2018 Jun 15;200(12):4059-4067. (PMID: 29728510)
Curr HIV/AIDS Rep. 2010 May;7(2):69-76. (PMID: 20425560)
AIDS Res Hum Retroviruses. 2021 Jan;37(1):24-33. (PMID: 33019813)
Elife. 2022 Jan 14;11:. (PMID: 35029144)
Nat Aging. 2022 Jul;2(7):644-661. (PMID: 36277076)
Aging (Albany NY). 2019 Jan 21;11(2):303-327. (PMID: 30669119)
Aging (Albany NY). 2017 Feb 23;9(3):687-705. (PMID: 28237978)
J Acquir Immune Defic Syndr. 2021 Aug 1;87(4):1102-1109. (PMID: 33765682)
Clin Epigenetics. 2021 Dec 17;13(1):224. (PMID: 34920739)
Clin Infect Dis. 2007 Dec 15;45(12):1593-601. (PMID: 18190322)
Immunity. 2013 Oct 17;39(4):633-45. (PMID: 24138880)
معلومات مُعتمدة: UM1 AI164559 United States AI NIAID NIH HHS; R01 HL160392 United States HL NHLBI NIH HHS; R01 MH134391 United States MH NIMH NIH HHS; R01 AG063846 United States AG NIA NIH HHS; R01AG063846 United States NH NIH HHS; UM1AI164559 United States NH NIH HHS
فهرسة مساهمة: Keywords: DNA methylation; HIV; epigenetic age; epigenetics; metformin; monocytes
المشرفين على المادة: 9100L32L2N (Metformin)
0 (Biomarkers)
تواريخ الأحداث: Date Created: 20230907 Date Completed: 20240111 Latest Revision: 20240716
رمز التحديث: 20240716
مُعرف محوري في PubMed: PMC10776116
DOI: 10.1111/acel.13926
PMID: 37675817
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-9726
DOI:10.1111/acel.13926