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Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation
Open accessAbstract
Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes.
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“Additionally, metformin, which is widely used to treat T2DM, activates AMPK, improves mitochondrial function, decreases age-associated inflammation and improves hyperglycaemia in people with obesity and prediabetes, as well as in HFD-fed mice238,239.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [238]
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Metadata
- Authors
- Bharath, L. P., Agrawal, M., McCambridge, G., Nicholas, D. A., Hasturk, H., Liu, J., Jiang, K., Liu, R., Guo, Z., Deeney, J., Apovian, C. M., Snyder-Cappione, J., Hawk, G. S., Fleeman, R. M., Pihl, R. M. F., Thompson, K., Belkina, A. C., Cui, L., Proctor, E. A., Kern, P. A., & Nikolajczyk, B. S.
- Affiliations
- Merrimack College (US)
- University of Kentucky (US)
- University of California San Diego (US)
- Boston University (US)
- Pennsylvania State University (US)
- Corresponding author
- Nikolajczyk, Barbara S.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 32
- Issue
- 1
- Pages
- 44-55.e6
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC7217133
- OpenAlex
- W3024177706
- Cited by
- 614
- References
- 90
- Citations by year
- 2026: 66 · 2025: 123 · 2024: 110 · 2023: 120 · 2022: 83 · 2021: 81 · 2020: 29
- FWCI
- 56.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UKnowledge (University of Kentucky) (submittedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, autophagy, mitochondrial function, inflammaging, Th17 cells, CD4+ T cells, aging, STAT3, IL-17A, redox imbalance, mitophagy, healthspan
- MeSH terms
- Adult, Aging, Autophagy, Humans, Hypoglycemic Agents, Inflammation, Metformin, Middle Aged, Mitochondria
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