3 replies to this topic

[maxwatt]

The implication seems to be that enhanced activation of SIRT6 will lengthen telomeres. Resveratrol, Silibin and other sirtuin enhancing substances probably activate SIRT6. Therefore these substances likely enhance telomere length.

Nature , | doi:10.1038/nature06736; Received 3 December 2007; Accepted 23 January 2008; Published online 12 March 2008

SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin

Eriko Michishita1,5, Ronald A. McCord1,5, Elisabeth Berber1,5, Mitomu Kioi2, Hesed Padilla-Nash6, Mara Damian1,5, Peggie Cheung3, Rika Kusumoto8, Tiara L. A. Kawahara4, J. Carl Barrett7,9, Howard Y. Chang4, Vilhelm A. Bohr8, Thomas Ried6, Or Gozani3 & Katrin F. Chua1,5



The Sir2 deacetylase regulates chromatin silencing and lifespan in Saccharomyces cerevisiae1, 2. In mice, deficiency for the Sir2 family member SIRT6 leads to a shortened lifespan and a premature ageing-like phenotype3. However, the molecular mechanisms of SIRT6 function are unclear. SIRT6 is a chromatin-associated protein3, but no enzymatic activity of SIRT6 at chromatin has yet been detected, and the identity of physiological SIRT6 substrates is unknown. Here we show that the human SIRT6 protein is an NAD+-dependent, histone H3 lysine 9 (H3K9) deacetylase that modulates telomeric chromatin. SIRT6 associates specifically with telomeres, and SIRT6 depletion leads to telomere dysfunction with end-to-end chromosomal fusions and premature cellular senescence. Moreover, SIRT6-depleted cells exhibit abnormal telomere structures that resemble defects observed in Werner syndrome, a premature ageing disorder4, 5. At telomeric chromatin, SIRT6 deacetylates H3K9 and is required for the stable association of WRN, the factor that is mutated in Werner syndrome4, 5. We propose that SIRT6 contributes to the propagation of a specialized chromatin state at mammalian telomeres, which in turn is required for proper telomere metabolism and function. Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome.

[niner]

I don't see where SIRT6 lengthens the telomeres, just that it is needed to help them function properly. So if it is missing or dysfunctional, then you have a real problem, but I'm not sure making it work better is going to make a big difference.

[maxwatt]

I don't see where SIRT6 lengthens the telomeres, just that it is needed to help them function properly. So if it is missing or dysfunctional, then you have a real problem, but I'm not sure making it work better is going to make a big difference.

Probably not make them grow longer, but the length will be greater in a population of cells with increased SIRT6 activity as compared to a population with lesser SIRT6 activity. Slowing the average rate at which telomere length shortens should increase longevity. If SIRT6 activity is not optimum, then increasing it would help. It seems possible, even probable, that decreased SIRT6 activity is a concommitant of human aging.

If anyone needs access to the full paper, let me know.

[inawe]

Yes, SIRT6 has been in the news recently. Seems it's "involved in regulation of life-span by nutrient availability":

FEBS Lett. 2008 Mar 5;582(5):543-8. Epub 2008 Jan 31.
Regulation of SIRT6 protein levels by nutrient availability.Kanfi Y, Shalman R, Peshti V, Pilosof SN, Gozlan YM, Pearson KJ, Lerrer B, Moazed D, Marine JC, de Cabo R, Cohen HY.
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.

Sirtuins have been shown to regulate life-span in response to nutritional availability. We show here that levels of the mammalian sirtuin, SIRT6, increased upon nutrient deprivation in cultured cells, in mice after fasting, and in rats fed a calorie-restricted diet. The increase in SIRT6 levels is due to stabilization of SIRT6 protein, and not via an increase in SIRT6 transcription. In addition, p53 positively regulates SIRT6 protein levels under standard growth conditions but has no role in the nutrient-dependent regulation of SIRT6. These observations imply that at least two sirtuins are involved in regulation of life-span by nutrient availability.

PMID: 18242175