Four papers on Sestrin, with the first a 2021 review:
“Sestrin 2 (Sesn2) is a member of the evolutionarily conserved and stress-inducible sestrin family. In mammals, this family is composed of Sesn1–3, and Sesn2 is the main member that responds to oxidative stress.
Sesn2 inhibits mammalian target of rapamycin (mTOR)-mediated cell over-proliferation by activating adenosine monophosphate-activated protein kinase (AMPK) and its kinase activity. Sesn2 also regulates redox balance by directly exerting antioxidant enzyme activity and regulating antioxidant signaling.
Inflammation, which is not regulated by oxidative stress, also plays an important role in cardiovascular diseases (CVDs). Sesn2 is involved in inflammation and immune regulation in many systems.
There is a positive feedback loop between Sesn2 and Nrf2:
Sesn2 and p62 are expressed under oxidative stress. Sesn2 binds to ULK1 and p62 to form a functional complex, which promotes p62 phosphorylation, promoting p62-dependent autophagy degradation of Keap1.
Consequently, Nrf2 accumulates in cells, transfers to the nucleus, and promotes transcriptional activation of genes controlled by antioxidant response elements (ARE).
Circulating Sesn2 levels are elevated in a variety of CVDs, such as coronary heart disease, heart failure and atrial fibrillation, which indicates that Sesn2 is induced and plays a protective role in CVDs.”
https://www.sciencedirect.com/science/article/abs/pii/S0891584920316270 “Sestrin 2, a potential star of antioxidant stress in cardiovascular diseases” (not freely available)
A second paper was also a 2021 review:
“Sestrin2 acts as an antioxidant protein that diminishes accumulation of ROS and inhibits mTORC1 signaling. Both accumulation of ROS and activation of mTORC1 are associated with aging and age-related diseases.
Since plasma sestrin2 levels in patients with CAD and those with carotid atherosclerosis were shown to be high, it remains unclear whether or not an exogenous administration of sestrin2 could be beneficial for prevention of atherosclerotic disease.”
https://www.mdpi.com/1422-0067/22/3/1200/htm “The Protective Role of Sestrin2 in Atherosclerotic and Cardiac Diseases”
A third paper was a 2020 human study:
“Sesn 1 and Sesn 2 levels were significantly reduced in sarcopenic compared to non-sarcopenic subjects. It can be concluded that sarcopenia can be diagnosed at the early stage by using serum sestrin as one potential biomarker.”
https://link.springer.com/article/10.1007/s40520-020-01642-9 “Serum sestrins: potential predictive molecule in human sarcopenia” (not freely available)
A fourth paper was a 2020 rodent study:
“Sulforaphane (SFN) alleviated hematological variations, oxidative stress, heart dysfunction and structure disorder, and cardiomyocyte apoptosis induced by potassium dichromate. Moreover, SFN:
- Reduced p53;
- Cleaved caspase-3, Bcl2-associated X protein, nuclear factor kappa-B, and interleukin-1β levels; and
- Increased Sesn2, Nrf2, heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and phosphorylated AMPK levels.
This study demonstrated that SFN ameliorates Cr(VI)-induced cardiotoxicity via activation of the Sesn2/AMPK/Nrf2 signaling pathway.”
https://pubs.rsc.org/en/content/articlelanding/2020/mt/d0mt00124 “Sulforaphane attenuates hexavalent chromium-induced cardiotoxicity via the activation of the Sesn2/AMPK/Nrf2 signaling pathway” (not freely available)
I found these studies as well as the previous post Cow milk causes disease from their citing a 2015 study The antioxidant function of sestrins is mediated by promotion of autophagic degradation of Keap1 and Nrf2 activation and by inhibition of mTORC1 (not freely available).