Monday, December 6, 2021
Mitochondrial Health

Aging and activating the heat shock response.



SPONSOR – Longevity.Technology – https://www.longevity.technology/?utm_source=youtube&utm_medium=social&utm_campaign=SSSheartshock

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.

TIMESTAMPS
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

REFERENCES
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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Icons in intro; “https://www.freepik.com/free-photos-vectors/background”Background vector created by freepik – www.freepik.com

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27 thoughts on “Aging and activating the heat shock response.
  1. I'm certainly more encouraged than becoming actively discouraged by the sum total of the vid's overall message.
    Here's me been long term drinking pineapple laced black tea and munching on capers for their very quercetin content, blind to the fact that …Well – we don't know yet!
    All things considered, with my brocolli and alfalfa seeds reordered just this morning, I'm at the very least bathing in sulphorophane's positive glow, even before I learned of their favourable HSF1 involvenent less than 2 minutes ago. Makes my 36 hour fast that I'm currently engaging in all the more worthwhile…in the grand scheme of things.
    Two turmeric coloured thumbs pointing indeed upwards in appreciation.

  2. I might be applying for a research MPhil at the Babraham, atm im working as an intern at an early stage life science VC. Would love to have a chat about research life at cambs, as well as shooting some ideas around novel drug targets, have a couple in mind, would like to hear what you think.

  3. Boron in our diet regulates certain aspects of the functioning of heat shock proteins, in much the same way its used to insulate electrical wiring in space craft.

  4. An idea: Just to change things up every once in a while, you could do a vid about how the UK Govt became the first in the world to prioritise the "biology of ageing" as a critical healthcare mission. https://www.gov.uk/government/publications/life-sciences-vision/life-sciences-vision-html

    Lots of gems in the UK House of Lords report too, e.g. Prof Faragher's quote: “What I fear … is that this country misses the boat and that we push
    exclusively on technological interventions. That would be akin to when a polio vaccine was on the horizon and the Government deciding that the solution was to ask the British Motor Corporation to build thousands of iron lungs, because there was clearly an immediate market demand.”

    https://committees.parliament.uk/publications/4286/documents/43456/default/

    Keep up the great work! 🙂

  5. I have learned SO much from your channel over the last year while pursuing my masters in nutrition. May I ask what this cool program is you use for these videos for this amazing animation?

  6. another person you could interview:
    The Bioneer (aka Adam Sinicki). another big name to promote your channel, and reasonably easy to reach.
    He became known after posting "Exercises that Batman would do",
    Beyond Sports, He knows very little about the longevity spectrum, aside from trying Intermittent Fasting.
    The cool thing about him is he tries to make a balance between Functional Exercices (cross-fit, cardio). and Bodybuilding (weights) and mainly: The name of his channel "bionner", is connected to the fact he tries to control his biology, the idea of self hacking, as all we try to do.
    Another cool thing, he doesn't talk specifically about longevity, but always tries to promote health at any age, and really takes exercises to another level in order to accomplish it.
    He is from the United Kingdom, and will probably not lose the chance to promote his books and shirts if you allow it.
    If he says he needs the cachĂŞ to be in an interview, tell him he lost the chance to speak to the first immortal doctor (yes you).
    If you do not buy a Microphone for table, until the next interview, the State of California will receive a big Earthquake.

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