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Role of sphingolipids in senescence: implication in aging and age-related diseases
Magali Trayssac, … , Yusuf A. Hannun, Lina M. Obeid
Magali Trayssac, … , Yusuf A. Hannun, Lina M. Obeid
Published July 2, 2018
Citation Information: J Clin Invest. 2018;128(7):2702-2712. https://doi.org/10.1172/JCI97949.
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Category: Review Series

Role of sphingolipids in senescence: implication in aging and age-related diseases

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Abstract

Aging is defined as the progressive deterioration of physiological function with age. Incidence of many pathologies increases with age, including neurological and cardiovascular diseases and cancer. Aging tissues become less adaptable and renewable, and cells undergo senescence, a process by which they “irreversibly” stop dividing. Senescence has been shown to serve as a tumor suppression mechanism with clear desirable effects. However, senescence also has deleterious consequences, especially for cardiovascular, metabolic, and immune systems. Sphingolipids are a major class of lipids that regulate cell biology, owing to their structural and bioactive properties and diversity. Their involvement in the regulation of aging and senescence has been demonstrated and studied in multiple organisms and cell types, especially that of ceramide and sphingosine-1-phosphate; ceramide induces cellular senescence and sphingosine-1–phosphate delays it. These discoveries could be very useful in the future to understand aging mechanisms and improve therapeutic interventions.

Authors

Magali Trayssac, Yusuf A. Hannun, Lina M. Obeid

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Figure 2

Senescence and consequences for tissue homeostasis.

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Senescence and consequences for tissue homeostasis.
Senescence can have ...
Senescence can have beneficial effects when acute because it allows the tissue to adapt to stress. Senescent cells secrete proinflammatory molecules in order to recruit immune cells that can then lead to clearance of senescent cells in the damaged tissue. If the regenerative capacity is efficient, tissue homeostasis is maintained. Senescence is a tumor suppressor mechanism and has some beneficial effects during wound healing and fibrosis. Aging induces a decrease in the efficiency of this cycle of senescence/recruitment/clearance/regeneration. Senescence can have deleterious effects when chronic, worsening pathologies such as type 2 diabetes and atherosclerosis.
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