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The heat shock response is an evolutionarily conserved response that causes the upregulation of many “molecular chaperones” within a cell. These “molecular chaperones”, otherwise referred to as Heat shock proteins (Hsps), help unfolded proteins to re-fold, aid the assembly of protein complexes and help traffic proteins around a cell.
Although the response is named after its discovery in response to a heat-shock, the response is also activated in response to oxidative stress, viral invasion and glucose deprivation, all forms of cellular stress. The activation of heat shock proteins in times of cellular stress is therefore thought to be adaptive since it enables protein folding to be retained in detrimental conditions. A key mediator behind this response is HSF-1. Adding or removing copies of the gene encoding HSF1 in different model organisms has been shown to extend or reduce their lifespan, respectively. The maintenance of proteostasis within a cell is one of the hallmarks of aging and thus many studies reinforce the point that maintenance of a robust heat shock response is important for health and survival.
So, can activating the heat shock response be beneficial for healthspan? Well many molecules that can activate HSF1 have been identified and inhibitors of Hsp90 turn out to have senolytic activity. We will discuss this more in the video.
Intro – 00:00
Biochemistry of the heat shock response – 00:42
Heat shock proteins & aging – 04:45
Activating the heat shock response – 06:55
Senolytics – 08:20
Ritossa, F. A new puffing pattern induced by temperature shock and DNP in drosophila. Experientia 18, 571–573 (1962). https://doi.org/10.1007/BF02172188
Regulation of Aging and Age-Related Disease by DAF-16 and Heat-Shock Factor – https://doi.org/10.1126/science.1083701
Regulation of Hsf1 Function in the Heat Stress Response: Implications in Aging and Disease – https://doi.org/10.1146/annurev-biochem-060809-095203
Regulation of the mammalian heat shock factor 1 – https://doi.org/10.1111/febs.13999
Hsps and aging – https://doi.org/10.1016/j.tem.2008.12.005
Fuhrmann-Stroissnigg, H., Ling, Y.Y., Zhao, J. et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nat Commun 8, 422 (2017). https://doi.org/10.1038/s41467-017-00314-z
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