Bioenergetics Nrf2 and Spermidine; Mitochondria and Endoplasmic Reticulum

Hydrogen rich water reduces senescence by reducing ROS directly and indirectly by activating Nrf2.  Nrf2 activation slows cell aging in trisomy 21.

Mitophagy ultimately removes ROS producing mitochondria and replaces them with efficient cleaner mitochondria.

It is oxidative damage by ROS that damages the MAM mitochondrial associated membrane shared with the endoplasmic reticulum. That blocks the local production of melatonin and other antioxidants that protects the marriage of mitochondria and endoplasmic reticulum.  This results in less exchange of "goods and services" needed to safely produce energy.

Consequences?

Metabolic failure triggers SENESCENCE or CANCER. Both are age and and disease related.  Both lead to stem cell failure and decline.

Reversal from Nrf2 activators and spermidine restores metabolic success and REVERSES aging, carcinogenesis and stem cell failure, the ultimate cause of death.

p53 leads either to restoration or senescence and apoptosis depending on energetic capability/ROS ratio signaling.

Highlights

•

Hydrogen alleviates the senescence process of BMSCs in vivo.

•

Hydrogen decreases the intracellular ROS levels.

•

Hydrogen reduces the expression of senescence-related proteins p53 and p21.

•

Hydrogen alleviates senescence of BMSCs via ROS/p53/p21 pathway.

https://www.sciencedirect.com/science/article/abs/pii/S0753332218328403

Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo

Senescence has become a hot point issue in recent decades and requires urgent attention. As a novel and effective antioxidant, hydrogen has been proved to alleviate cellular senescence in endothelial cells in vitro. However, the effects and mechanisms of hydrogen on senescence in vivo are still unclear. In the present study, 12-month-old Sprague Dawley (SD) rats were intraperitoneal administration of hydrogen-rich saline (HRS, 10 ml/kg). Subsequently, bone marrow-derived stem cells (BMSCs) were harvested for the detection of hydrogen antisenescence effects and mechanisms. The results showed that the number of senescence-associated β-galactosidase (SA-β-Gal) positive cells was reduced in BMSCs from rats treated with HRS. BMSCs in rats treated with HRS possessed a better proliferation ability, showed more effectively tri-lineage differentiation potential, and had less percentage of cells in G1 cell cycle arrest than the control cells. Additionally, HRS administration inhibited the production of intracellular reactive oxygen species (ROS) and decreased the expression of senescence-related proteins p53 and p21. Our results revealed that hydrogen could alleviate cellular senescence in vivo. And the underlying mechanism of antisenescence effects of hydrogen in BMSCs was via the ROS/p53/p21 signaling pathway. Thus, hydrogen could be a new and convenient strategy for alleviating senescence and for therapy of age-related diseases.