Tuesday, October 19, 2021
Mitochondrial Health

The longevity sirtuin – what you need to know about SIRT6

SPONSOR: Longevity.Technology – https://www.longevity.technology/?utm_source=SSS&utm_medium=YouTube&utm_campaign=Sirt6

Sirtuins are highly conserved proteins that are involved in a variety of important cellular processes such as DNA repair, metabolism and circadian rhythms. The mammalian sirtuins (SIRT1-7) are a family of proteins that carry out NAD+-dependent protein deacylation and mono-ADP-ribosylation. These modifications on proteins can influence their stability, localisation within a cell and activity.

In the late 90s interest in sirtuins bloomed as it was found yeast lived 30% longer when they had an additional copy of a yeast sirtuin, Sir2. Similar studies have now been performed in mice, but whilst overexpression of SIRT1 in mice does not result in lifespan extension, overexpression of SIRT6 does. This has led to SIRT6 being referred to as the longevity sirtuin. However, there seems to be some sex- and mouse strain-dependent differences. So, in the remainder of the video, we will discuss what you need to know about SIRT6 including it’s proposed cellular activities, it’s association with longevity and how SIRT6 activation using allosteric activators could have future therapeutic potential.

Intro – 00:00
Sirtuins – 00:45
SIRT1, SIRT6 and longevity – 03:00
SIRT6 and DNA damage – 08:30
Activating SIRT6 – 09:50
Additional thoughts – 11:45

#longevity #science #latestresearch #TSSS

Roichman, A., Elhanati, S., Aon, M.A. et al. Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nat Commun 12, 3208 (2021). https://doi.org/10.1038/s41467-021-23545-7
Regulation of SIRT6 protein levels by nutrient availability – https://doi.org/10.1016/j.febslet.2008.01.019
Regulation of SIRT1 protein levels by nutrient availability – https://doi.org/10.1016/j.febslet.2008.06.005
Kanfi, Y., Naiman, S., Amir, G. et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483, 218–221 (2012). https://doi.org/10.1038/nature10815
Sirtuin activators and inhibitors: Promises, achievements, and challenges – https://doi.org/10.1016/j.pharmthera.2018.03.004
SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species – https://doi.org/10.1016/j.cell.2019.03.043
Huang, Z., Zhao, J., Deng, W. et al. Identification of a cellularly active SIRT6 allosteric activator. Nat Chem Biol 14, 1118–1126 (2018). https://doi.org/10.1038/s41589-018-0150-0

Check out @LifeXtenShow latest video – https://www.youtube.com/watch?v=q03CuLLLzHM

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 “The longevity sirtuin – what you need to know about SIRT6
  1. Awesome video as always! I’m currently taking fucoidan, quercetin, and fisetin daily because I think there’s good evidence these molecules extend healthy human lifespan at proper doses and it turns out there’s pretty good evidence that all 3 may be SIRT6 activators which would partially explain why they can extend healthy human lifespan.

  2. Think heard Cyanidin is sirt6 activator, iirc present in some berries. Also resveratrol indirectly does so too. "Tracking the resveratrol-bound TyrRS in the nucleus, the researchers determined that it grabs and activates the protein, PARP-1, a major stress response and DNA-repair factor thought to have a significance influence on lifespan. The scientists confirmed the interaction in mice injected with resveratrol. TyrRS's activation of PARP-1 led, in turn, to the activation of a host of protective genes including the tumor-suppressor gene p53 and the longevity genes FOXO3A and SIRT6."-https://www.sciencedaily.com/releases/2014/12/141222111940.htm

  3. In being tied to CR, I wonder how IF (including in different patterns / durations) would affect SIRT6 activation…. possibly coupled with various 'supplements' (e.g. NAD precursors). How easy is it to measure levels of SIRT6?

  4. Might the flavonoid cyanidin act as an effective SIRT6 activator?

    “The most potent SIRT6 activator, cyanidin, belonged to anthocyanidins, and produced a 55-fold increase in SIRT6 activity compared to the 3–10 fold increase for the others.”

    “the most prominent activators for SIRT6 among the flavonoids were the anthocyanidins, the universal plant pigment, responsible for the red, purple, and blue color in many fruits, vegetables and flowers. The most potent compound in the class of anthocyanidins, cyanidin, significantly increased the deacetylation activity of SIRT6. It is most abundant in red berries including bilberry, raspberry and cranberry. Studies have suggested that anthocyanidins, including cyanidin, may play important roles in helping to reduce the risk of many age-related diseases.”

  5. Have you thought about looking at bloodresult variations and aging? E.g markers of inflammation, blood urea, WBC, RBC etc and their changes over time. How they indicate internal aging and what we can do about it?

  6. This comment is not specific to this video but somewhat relates to your video "P53, cancer metabolism and NAD" and your article "GUARDIN THE GENOME; A LNCRNA UNITES P53, TELOMERES AND MIRNAS" and somewhat to your video on hyperbaric oxygen therapy since it is the opposite of hyperbaric oxygen therapy.
    I am talking about intermittent hypoxic training (IHT). Since IHT is readily available using hypoxic training masks and IHT activates both p53 and heat shock proteins (another interesting protein): (https://www.rosalbacourtney.com/intermittent-hypoxic-training-altitude-training-at-sea-level/) (https://www.frontiersin.org/articles/10.3389/fphys.2017.00811/full#:~:text=Acclimation%20to%20heat%20or%20hypoxic,function%20and%20reduce%20systemic%20inflammation.), could you comment on the possible benefit of IHT to healthspan or lifespan? Thank you for all the wonderful information you provide.

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