Review Volume 13, Issue 1 pp 1510—1527
PAM (PIK3/AKT/mTOR) signaling in glia: potential contributions to brain tumors in aging
- 1 Department of Neuroscience Lewis Katz School of Medicine at Temple University Philadelphia, PA 19140, USA
- 2 Department of Neurosurgery Temple University Hospital Philadelphia, PA 19140, USA
Received: September 29, 2020 Accepted: December 10, 2020 Published: January 5, 2021https://doi.org/10.18632/aging.202459
How to Cite
Copyright: © 2020 Duggan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Despite a growing proportion of aged individuals at risk for developing cancer in the brain, the prognosis for these conditions remains abnormally poor due to limited knowledge of underlying mechanisms and minimal treatment options. While cancer metabolism in other organs is commonly associated with upregulated glycolysis (i.e. Warburg effect) and hyperactivation of PIK3/AKT/mTOR (PAM) pathways, the unique bioenergetic demands of the central nervous system may interact with these oncogenic processes to promote tumor progression in aging. Specifically, constitutive glycolysis and PIK3/AKT/mTOR signaling in glia may be dysregulated by age-dependent alterations in neurometabolic demands, ultimately contributing to pathological processes otherwise associated with PIK3/AKT/mTOR induction (e.g. cell cycle entry, impaired autophagy, dysregulated inflammation). Although several limitations to this theoretical model exist, the consideration of aberrant PIK3/AKT/mTOR signaling in glia during aging elucidates several therapeutic opportunities for brain tumors, including non-pharmacological interventions.