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. 2022 Mar 3;2:797320. doi: 10.3389/fragi.2021.797320

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Copyright © 2022 Li and Kim.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Summary of the impact each sphingolipid species have on the hallmarks of aging discussed in this review. (A) Early sphingolipid research uncovered the differential regulation of cell fate through the modulation of signaling pathways. Ceramide upregulation resulted in the activation of apoptosis and cell growth arrest while S1P is required for proper cellular growth. This is now known as the “Sphingolipid Rheostat” and is one of the fundamental concepts of sphingolipid biology. In age-related disease such as Alzheimer’s Disease (AD), Huntington’s Disease (HD), Parkinson’s Disease (PD) and Cancer, the alterations in sphingolipid metabolism follows the rheostat. Changes in either pro-apoptotic or pro-survival signaling pathway is negatively correlated in the other. (B) Contributions of the major sphingolipid metabolites to the hallmarks of aging as mentioned in this review.