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Review
. 2018 Dec;11(4):189-194.
doi: 10.1016/j.hemonc.2017.08.001. Epub 2017 Oct 19.

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

Mohammadhossein Khorraminejad-Shirazi  1 , Mohammad Farahmandnia  2 , Bahareh Kardeh  2 , Alireza Estedlal  2 , Sina Kardeh  2 , Ahmad Monabati  3
Affiliations
Free article
Review

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

Mohammadhossein Khorraminejad-Shirazi et al. Hematol Oncol Stem Cell Ther. 2018 Dec.
Free article

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.

Keywords: AMPK; Aging; Rejuvenation; SIRT1; Stem cell therapy; mTORC1.

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