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CD36 initiates the secretory phenotype during the establishment of cellular senescence.


Maximus Peto’s Commentary

This group reports that CD36 is apparently involved in activation of SASP and “a full senescent state”. CD36 was apparently “strictly required” for “secretory molecule production”. And, interestingly, amyloid-beta was reportedly sufficient to induce CD36-dependent SASP activation.


CD36 initiates the secretory phenotype during the establishment of cellular senescence.
EMBO Rep. 2018 Jun;19(6). pii: e45274.
Chong M, Yin T, Chen R, Xiang H, Yuan L, Ding Y, Pan CC, Tang Z, Alexander PB, Li QJ, Wang XF
DOI: 10.15252/embr.201745274
PubMed publication date (edat): 5/20/2018

Abstract

Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular mechanisms responsible for generating a SASP in response to senescent stimuli remain largely obscure. Here, using unbiased gene expression profiling, we discover that the scavenger receptor CD36 is rapidly upregulated in multiple cell types in response to replicative, oncogenic, and chemical senescent stimuli. Moreover, ectopic CD36 expression in dividing mammalian cells is sufficient to initiate the production of a large subset of the known SASP components via activation of canonical Src-p38-NF-κB signaling, resulting in the onset of a full senescent state. The secretome is further shown to be ligand-dependent, as amyloid-beta (Aβ) is sufficient to drive CD36-dependent NF-κB and SASP activation. Finally, loss-of-function experiments revealed a strict requirement for CD36 in secretory molecule production during conventional senescence reprogramming. Taken together, these results uncover the Aβ-CD36-NF-κB signaling axis as an important regulator of the senescent cell fate via induction of the SASP.

PMID: 29777051
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989758/

Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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