#Sirt6

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 Then I started looking into its active constituents (besides iodine); here are my notes (now out of date) -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

#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

#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

#Sirt6 #Osteoarthritis

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

Deacetylated STAT5 by Sirt6 fails nuclear import

In contrast, Sirt6p21->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, inDMM #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 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 #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 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

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