Cell Transfiguration to Ageless Health is an Epigenic Process

Here, an HDAC3 inhibitor (histone deacetylase inhibitor) restores the acetylation of Peroxisome Proliferation–Activated Receptor and Klotho increases and protects kidneys (other tissue and organs!)

Exercise and fasting also performs this function via the action of beta hydroxybutyrate, an HDAC(3) inhibitor.

Aging methylates the Klotho promoter gene.  Hydrogen rich water or endogenous H2S can demethylate the CGG promoter site of Klotho after histone is removed by the HDAC inhibitor.  

The sequential combination action of HDAC and hydrogen turns genes on.  Aging, loss of the solubility ATP provides, may be caused by ATP loss for one of two reasons.  Protection from cell energy failure or cell solubility failure.  (Please note that pioglitazone, a peroxide proliferation gamma agonist promotes fatty acid oxidation, producing beta hydroxybutyrate and restores Klotho gene promoter switch to on.)

Beta hydroxybutyrate, unlike some HDAC inhibitors, also serves as the starvation gene set promoter which increases mitochondrial biogenesis and ATP is directly proportional to mitochondria volume. Thus cell energy and solubility increase and the cell appears to be younger.

Summary: beta hydroxybutyrate AND hydrogen turns genes back on that promote health and youthful epigenic restoration.  

Aging, inflamaging turns genes off.

Restoring gene switches to on optimally occurs when antioxidant capacity is also optimum and proteostasis is optimum.  

Therefore, sulforaphane (antioxidant capacity) and wheat germ (proteostasis) completes the transfiguration into youthful dynamic cells and in numerous species and human cells increases healthspan and lifespan by 30%!

Beta hydroxybutyrate is downstream of Peroxisome Proliferation–Activated Receptor γ and had a direct effect that is also provided by sodium butyrate which is 3% of butter.  The French version of the Mediterranean diet before Paula Dean is full of this HDAC inhibitor!

http://www.sciencedirect.com/science/article/pii/S0085253817301588

Klotho restoration via acetylation of Peroxisome Proliferation–Activated Receptor γ reduces the progression of chronic kidney disease

Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho (1) expression closely correlates with the development and progression of chronic kidney disease (CKD). Klotho is also a downstream gene of Peroxisome Proliferation–Activated Receptor γ (PPARγ), a major transcription factor whose functions are significantly affected by post-translational modifications including acetylation. However, whether PPARγ acetylation regulates renal Klotho expression and function in CKD is unknown. Here we test whether renal damage and reduced Klotho expression in the adenine CKD mouse model can be attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A. This inhibition up-regulated Klotho mainly through an enhancement of PPARγ acetylation, stimulation of PPARγ binding to Klotho promoter, and PPARγ-dependent increase in Klotho transcription, with a substantial control of the regulation occurring via PPARγ acetylations on K240 and K265. Consistently trichostatin A–induced reversal of Klotho loss and renoprotective effects were abrogated in PPARγ knockout mice, supporting that PPARγ is an essential acetylation target for Klotho restoration and renal protection. Intriguingly, the kidneys of adenine-fed CKD mice displayed deregulated HDAC3 up-regulation. Selective HDAC3 inhibition effectively alleviated Klotho loss and kidney injury, whereas the protective effects were largely abolished when Klotho was knocked down by siRNA, suggesting that aberrant HDAC3 and Klotho loss are crucial components involved in the renal damage of mice with CKD. Our study identified an important signaling cascade and key components contributing to the pathogenesis of CKD. Thus, targeting Klotho loss by HDAC3 inhibition has promising therapeutic potential for the reduction of CKD progression.