Aging and stem cell therapy: AMPK as an applicable pharmacological target for rejuvenation of aged stem cells and achieving higher efficacy in stem cell therapy

Hematology/oncology and Stem Cell Therapy
Mohammadhossein Khorraminejad-ShiraziAhmad Monabati

Abstract

In recent years, tissue regeneration has become a promising field for developing stem cell-based transplantation therapies for human patients. Adult stem cells are affected by the same aging mechanisms that involve somatic cells. One of the mechanisms involved in cellular aging is hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and disruption of 5' adenosine monophosphate-activated protein kinase (AMPK). Aging of stem cells results in their impaired regenerative capacity and depletion of stem cell pools in adult tissue, which results in lower efficacy of stem cell therapy. By utilizing an effective therapeutic intervention for aged stem cells, stem cell therapy can become more promising for future application. mTORC1 inhibition is a practical approach to preserve the stem cell pool. In this article, we review the dynamic interaction between sirtuin (silent mating type information regulation 2 homolog) 1, AMPK, and mTORC1. We propose that using AMPK activators such as 5-aminoimidazole-4-carboxamide ribonucleotide, A769662, metformin, and oxidized nicotinamide adenine dinucleotide (NAD+) are practical ways to be employed for achieving better optimized results in stem cell-based transplantation therapies.

Citations

Feb 16, 2018·Journal of Biological Research·Umesh Chandra Halder
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Xueke ZhouXin Li
Feb 23, 2020·International Journal of Molecular Sciences·Loubna MaziniGabriel Malka
Nov 7, 2019·World Journal of Stem Cells·Mohammadhossein Khorraminejad-ShiraziPouria Mosaddeghi
Nov 25, 2020·Bulletin of Experimental Biology and Medicine·A P LykovO V Poveshchenko
Sep 8, 2019·Journal of Theoretical Biology·Mohammadreza DorvashIman Tavassoly
Jan 29, 2021·World Journal of Stem Cells·Lin-Li Jiang, Lei Liu
Nov 9, 2020·Molecular Aspects of Medicine·George HajishengallisTriantafyllos Chavakis
Dec 6, 2020·Burns : Journal of the International Society for Burn Injuries·Sina KardehShima Faezi-Marian

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