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Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

[ Vol. 13 , Issue. 4 ]

Author(s):

Kenneth Maiese   Pages 329 - 340 ( 12 )

Abstract:


Life expectancy continues to increase throughout the world, but is accompanied by a rise in the incidence of non-communicable diseases. As a result, the benefits of an increased lifespan can be limited by aging-related disorders that necessitate new directives for the development of effective and safe treatment modalities. With this objective, the mechanistic target of rapamycin (mTOR), a 289-kDa serine/threonine protein, and its related pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), proline rich Akt substrate 40 kDa (PRAS40), AMP activated protein kinase (AMPK), Wnt signaling, and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), have generated significant excitement for furthering novel therapies applicable to multiple systems of the body. Yet, the biological and clinical outcome of these pathways can be complex especially with oversight of cell death mechanisms that involve apoptosis and autophagy. Growth factors, and in particular erythropoietin (EPO), are one avenue under consideration to implement control over cell death pathways since EPO can offer potential treatment for multiple disease entities and is intimately dependent upon mTOR signaling. In experimental and clinical studies, EPO appears to have significant efficacy in treating several disorders including those involving the developing brain. However, in mature populations that are affected by aging-related disorders, the direction for the use of EPO to treat clinical disease is less clear that may be dependent upon a number of factors including the understanding of mTOR signaling. Continued focus upon the regulatory elements that control EPO and mTOR signaling could generate critical insights for targeting a broad range of clinical maladies.

Keywords:

Akt, aging, aging-related disorders, Alzheimer’s disease, AMP activated protein kinase (AMPK), apoptosis, autophagy, cardiovascular disease; caspase, diabetes mellitus, epidermal growth factor, erythropoietin, hamartin (tuberous sclerosis 1)/tuberin (tuberous sclerosis 2) (TSC1/TSC2), Huntington’s disease, hypoxia-inducible factor 1, insulin, lifespan, mechanistic target of rapamycin (mTOR), mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), nicotinamide, nicotinamide adenine dinucleotide (NAD+), non-communicable diseases, oxidative stress, phosphoinositide 3 –kinase (PI 3-K), programmed cell death, proline rich Akt substrate 40 kDa (PRAS40), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), sirtuin, stem cells, wingless, Wnt, Wnt1 inducible signaling pathway protein 1 (WISP1).

Affiliation:

Cellular and Molecular Signaling, Newark, New Jersey 07101, USA.



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