shikimic acid, skin cell senence, proteostasis, Pinus strobus - brief notes
Modern Healthspan released a video on an article that reports that shikimic acid reduced markers of UV light induced cellular senescence in cultured dermal fibroblasts, increased SIRT1 activity and restored proteostasis. As MH suggests in the video, these findings could have much broader implications.
Video:
Research article:
Martinez-Gutierrez et al. (2021) https://www.aging-us.com/article/203010/text
"SA reverted misfolded protein accumulation upon senescence, an effect that was abrogated by EX-527. Consistently, SA induced an increase in the levels of the chaperone BiP, resulting in a downregulation of unfolded protein response (UPR) signaling and UPR-dependent autophagy, avoiding their abnormal hyperactivation during senescence. SA did not directly activate SIRT1 in vitro, suggesting that SIRT1 is a downstream effector of SA signaling specifically in the response to cellular senescence. Our study not only uncovers a shikimic acid/SIRT1 signaling pathway that prevents cellular senescence, but also reinforces the role of sirtuins as key regulators of cell proteostasis.
The Amide I deconvolution allowed us to estimate changes in the secondary protein structure, which revealed a global increase of the β-sheet/α-helix ratio in the proteins of these cells upon UVB (Figure 4G, 4H and Supplementary Figure 6D). This ratio increase has been previously linked to increased levels of misfolded proteins [63–66], suggesting that SA prevents the accumulation of misfolded proteins accumulated upon UV. Strikingly, while SA treatment inhibited these levels well below the ratio observed in control cells in the absence of UVB irradiation, treatment with EX-527 completely reverted the effect of SA (Figure 4G, 4H and Supplementary Figure 6D). This suggested that the SIRT1-dependent effect of SA on senescence may be associated with an altered pattern of misfolded and/or aggregated proteins, which pointed to an effect on UPR and/or autophagy. Interestingly, while SA treatment induced upregulation of chaperone BiP (also known as GPR78), a major regulator of cell proteostasis, that effect was partially reverted by EX-527."
Could shikimic acid be a poor person's ISRIB?
For all the vexation caused by reading the vitriol and nonsense in YT comments, there are sometimes a few gems to be found that make it worthwhile overall. One of MH's viewers commented that Eastern white pine (Pinus strobus) needles can be used to make tea and are a source of shikimic acid. We have mainly loblolly pine in my area, which is unsuitable since it apparently can contain toxic constituents, so I intend to purchase a white pine and perhaps make it into a bonsai.
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