Metformin-enhances resilience via hormesis

Edward J Calabrese; Evgenios Agathokleous; Rachna Kapoor; Gaurav Dhawan; Walter J Kozumbo; Vittorio Calabrese

doi:10.1016/j.arr.2021.101418

Metformin-enhances resilience via hormesis

Ageing Res Rev. 2021 Nov:71:101418. doi: 10.1016/j.arr.2021.101418. Epub 2021 Aug 5.

Authors

Edward J Calabrese¹, Evgenios Agathokleous², Rachna Kapoor³, Gaurav Dhawan⁴, Walter J Kozumbo⁵, Vittorio Calabrese⁶

Affiliations

¹ Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA, 01003, USA. Electronic address: edwardc@schoolph.umass.edu.
² Key Laboratory of Agrometeorology of Jiangsu Province, Department of Ecology, School of Applied Meteorology, Nanjing University of Information Science & Technology, Nanjing, 210044, China. Electronic address: evgenios@nuist.edu.cn.
³ Saint Francis Hospital and Medical Center, Hartford, CT, USA. Electronic address: dr.rachnakapoor23@gmail.com.
⁴ Sri Guru Ram Das (SGRD), University of Health Sciences, Amritsar, India. Electronic address: drgdhawan@icloud.com.
⁵ 7 West Melrose Avenue, Baltimore, MD, 21210, USA. Electronic address: kozumbo@gmail.com.
⁶ Department of Biomedical and Biotechnological Sciences, School of Medicine University of Catania, Via Santa Sofia 97, Catania, 95123, Italy. Electronic address: calabres@unict.it.

PMID: 34365027
DOI: 10.1016/j.arr.2021.101418

Abstract

The present paper demonstrates that metformin (MF) induced a broad spectrum of hormetic biphasic dose responses in a wide range of experimental studies, affecting multiple organ systems, cell types, and endpoints enhancing resilience to chemical stresses in preconditioning and co-current exposure protocols. Detailed mechanistic evaluations indicate that MF-induced hormetic-adaptive responses are mediated often via the activation of adenosine monophosphate-activated kinase (AMPK) protein and its subsequent upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Hormesis-induced protective responses by MF are largely mediated via a vast and highly integrated anti-inflammatory molecular network that enhances longevity and delays the onset and slows the progression of neurodegenerative and other chronic diseases.

Keywords: AMPK; Aging; Hormesis; Metformin; Neuroprotection; Nrf2.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Hormesis*
Longevity
Metformin* / pharmacology

Substances

Metformin