Title:Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy
Volume: 13
Issue: 4
Author(s): Kenneth Maiese
Affiliation:
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).
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.
