RhyothemisNov 26, 2023

Vera Gorbunova at ARDD2023: Transcriptomic and proteomic signatures of longevity
https://youtu.be/DjYHihUfHq8?si=j73curN9IHGhuj35

I ❤️ Dr Gorbunova
I ❤️ fucoidan

I've been a fan of fucoidan for years, before I found out it is a SIRT6 activator. I started eating wakame as a source of iodine & noticed a reduction in 'aches & pains'. Then I started looking into its active constituents (besides iodine); here are my notes (now out of date) -
https://rhyobrain.blogspot.com/2020/11/wakame-and-fucoidan.html

#LINE1 #retrotransposons #SIRT6 #fucoidan #aging #inflammation #NaturalProducts #FunctionalFoods

Vera Gorbunova at ARDD2023: Transcriptomic and proteomic signatures of longevity

YouTube
Hao YinMar 4, 2023

#Sirt6 deacetylates #YAP & #TAZ->
⏬their transcriptional activities
⏬TGFβ1-induced Fibrotic reprogramming of #HepaticStellateCell
in diet-induced🐭#LiverFibrosis

TAZ seems more sensitive to Sirt6 than YAP🤓

#MALFD

Dr. Charlie Dong lab FASEB J 2022
https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.202200522R

Hao YinFeb 13, 2023

#EndothelialCell #Sirt6 deficiency->
⏫#TissueFactor/F3+vascular inflammation genes Cox2, VCAM1, TNFα, MCP1
Accelerated Carotid arterial #Thrombosis (Rose bengal)

A role in atherosclerotic plaque stability?😃

Dr. Christian Matter lab JMCC 2022
https://www.jmcc-online.com/article/S0022-2828(22)00565-X/fulltext

Hao YinDec 19, 2022

#Sirt6 #Osteoarthritis

Sirt6⏬#Senescence & IL15-JAK3-STAT5-inflammation in adult #Chondrocyte

Deacetylated STAT5 by Sirt6 fails nuclear import

In contrast, Sirt6⏫p21->Senescence in embryonic chondrocyte

Dr. Ming-liang Ji & Jun Lu lab Nature Comms 2022
https://www.nature.com/articles/s41467-022-35424-w

An interesting chondrotrophic nanoparticle is used to deliver MDL-800, Sirt6 activator, in🐭DMM #Osteoarthritis

Chondrocyte-specific aptamer tgg2-functionalized PEGylated PAMAM nanoparticle

Originally used for microRNA Annals of the Rheumatic Diseases 2021
https://ard.bmj.com/content/80/3/356.abstract

Sirt6 attenuates chondrocyte senescence and osteoarthritis progression - Nature Communications

Ji and colleagues identify Sirt6 as a regulator of chondrocyte senescence. Mechanistically, Sirt6 physically interacts with STAT5 and deacetylates it at K163, which reduces the IL-15/JAK3-induced STAT5 translocation from cytoplasm to nucleus.

Nature
Hao YinDec 12, 2022

#Sirt6 control of #EndothelialCell #FattyAcid transport links #Diabetes microvascular dysfunction with #HeartFailurewithPreservedEjectionFraction #HFpEF

EC Sirt6->
⏬H3K9ac PPARγ promoter
⏬CD36,FABP4/5
⏬🐭 Heart Lipid

Dr. Zheng Gen Jin lab Circ Res 2022
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318988

SIRT6 Mitigates Heart Failure With Preserved Ejection Fraction in Diabetes

Background: Heart failure with preserved ejection fraction (HFpEF) is a growing health problem without effective therapies. Epidemiological studies indicate that diabetes is a strong risk factor for

Circulation Research
Hao YinNov 30, 2022

#Sirt6 #VascularInflammation

MRTF-A as a deacetylation target of Sirt6 in #EndothelialCell

Deactylated MRTF-A stays in cytoplasm, failing to mediate oxLDL-induced EC ICAM1

An OxLDL-DNMT1 cacade epigenetically silences Sirt6 expression

Dr. Qianyun Wang, Tianfa Li & Qianwen Zhao labs Cell Death Discov 2022
https://www.nature.com/articles/s41420-022-00903-y

SIRT6 mediates MRTF-A deacetylation in vascular endothelial cells to antagonize oxLDL-induced ICAM-1 transcription - Cell Death Discovery

Oxidized low-density lipoprotein (oxLDL), a known risk factor for atherosclerosis, activates the transcription of adhesion molecules (ICAM-1) in endothelial cells. We previously showed that myocardin-related transcription factor A (MRTF-A) mediates oxLDL-induced ICAM-1 transcription. Here we confirm that ICAM-1 transactivation paralleled dynamic alterations in MRTF-A acetylation. Since treatment with the antioxidant NAC dampened MRTF-A acetylation, MRTF-A acetylation appeared to be sensitive to cellular redox status. Of interest, silencing of SIRT6, a lysine deacetylase, restored MRTF-A acetylation despite the addition of NAC. SIRT6 directly interacted with MRTF-A to modulate MRTF-A acetylation. Deacetylation of MRTF-A by SIRT6 led to its nuclear expulsion thus dampening MRTF-A occupancy on the ICAM-1 promoter. Moreover, SIRT6 expression was downregulated with oxLDL stimulation likely owing to promoter hypermethylation in endothelial cells. DNA methyltransferase 1 (DNMT1) was recruited to the SIRT6 promoter and mediated SIRT6 repression. The ability of DNMT1 to repress SIRT6 promoter partly was dependent on ROS-sensitive serine 154 phosphorylation. In conclusion, our data unveil a novel DNMT1-SIRT6 axis that contributes to the regulation of MRTF-A acetylation and ICAM-1 transactivation in endothelial cells.

Nature
Hao YinNov 29, 2022

#SIRT6 N308K/A313S, a #Centenarian variant
⏬deacetylase/deacylase
⏫mono-ADP-ribosylase
⏬LINE1 retrotransposition
⏫DNA repair
⏫tumor killing

Lamin A is mADP-ribosylated by Sirt6!

Love to explore its benefit over blood vessels!

Dr. Andrei Seluanov, Yousin Suh, Vera Gorbunova labs EMBO J 2022
https://www.embopress.org/doi/full/10.15252/embj.2021110393

Hao YinNov 20, 2022

12q, an optimized small chemical activator of #Sirt6
Comprehensive analyses vs MDL-800->
⏫Sirt6 deacetylase & demyristoylase activities
⏫Anti-#PancreaticDuctalAdenoCarcinoma activity

Look forward to more studies on its Non-tumoral benefits?🧐

Dr. Shengyong Yang lab J Med Chem 2022
https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.0c01183