IP6K3 Gene Deletion Mice Extended Lifespan And IP6K3 Was Upregulated By Dexamethasone Treatment

[yogiri]

Inositol Hexakisphosphate Kinase 3 Regulates Metabolism and Lifespan in Mice
Inositol Hexakisphosphate Kinase 3 Regulates Metabolism and Lifespan in Mice
...IP6K3 mRNA is elevated by dexamethasone in human primary myotubes.

is there any possible way can down regulate ip6k3?

 

[yogiri]

Inositol pyrophosphates mediate the effects of aging on bone marrow mesenchymal stem cells by inhibiting Akt signaling

 

[Mauritio]

interesting ! how long did they live longer on average ?

" Ip6k3−/− mice demonstrated lower blood glucose, reduced circulating insulin, deceased fat mass, lower body weight, increased plasma lactate, enhanced glucose tolerance, lower glucose during an insulin tolerance test, and reduced muscle Pdk4 expression under normal diet conditions. Notably, Ip6k3 deletion extended animal lifespan with concomitant reduced phosphorylation of S6 ribosomal protein in the heart. In contrast, Ip6k3−/− mice showed unchanged skeletal muscle mass and no resistance to the effects of high fat diet. The current observations suggest novel roles of IP6K3 in cellular regulation, which impact metabolic control and lifespan."

Sounds all great to me despite higher lactate.

 

[yogiri]

interesting ! how long did they live longer on average ?

" Ip6k3−/− mice demonstrated lower blood glucose, reduced circulating insulin, deceased fat mass, lower body weight, increased plasma lactate, enhanced glucose tolerance, lower glucose during an insulin tolerance test, and reduced muscle Pdk4 expression under normal diet conditions. Notably, Ip6k3 deletion extended animal lifespan with concomitant reduced phosphorylation of S6 ribosomal protein in the heart. In contrast, Ip6k3−/− mice showed unchanged skeletal muscle mass and no resistance to the effects of high fat diet. The current observations suggest novel roles of IP6K3 in cellular regulation, which impact metabolic control and lifespan."

Sounds all great to me despite higher lactate.

not sure how long it can extend.
it seems ip6k3 is elevated by glucocorticoid receptors and fasting
and ip7 is a sensor of energy it increased with aged in mesenchymal stem cells.

i was searching for what is PA1
PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation
"...PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter."

 

[GorillaHead]

This is super fascinating. I wonder how ip6 supplementation would fit in this.

 

[haidut]

Inositol Hexakisphosphate Kinase 3 Regulates Metabolism and Lifespan in Mice
Inositol Hexakisphosphate Kinase 3 Regulates Metabolism and Lifespan in Mice
...IP6K3 mRNA is elevated by dexamethasone in human primary myotubes.

is there any possible way can down regulate ip6k3?

I am not sure how valid is a study on a genetic mutant and indirect, predicted effects of a glucocorticoid when there is direct evidence in non-mutants that treatment with dexamethasone for just 3 days shortens lifespan by up to 25%.
Enhanced glucocorticoid feedback inhibition of hypothalamo-pituitary-adrenal responses to stress in adult rats neonatally treated with dexamethasone - PubMed
Long-lasting effects of neonatal dexamethasone treatment on spatial learning and hippocampal synaptic plasticity: involvement of the NMDA receptor complex - PubMed
Reduced Life Expectancy in Rats After Neonatal Dexamethasone Treatment | Pediatric Research
"...The glucocorticoid dexamethasone (Dex) is widely used in preterm infants for the prevention of chronic lung disease. However, major concern has arisen about the long-term sequelae of this therapy. Here we report that neonatal treatment with dexamethasone significantly shortens the lifespan by 25% of male rats (28.6 ± 1.1 to 21.3 ± 0.8 mo) and by 18% of female rats (26.9 ± 1.8 to 22.0 ± 0.7 mo). Histopathological examination indicated end-stage cardiac and renal failure as the cause of premature death. Furthermore, Dex- treated rats showed symptoms of hypertension at young adult age, which worsened with increasing age. Thus, a brief period of glucocorticoid treatment during early life results in untimely death presumably due to cardiovascular and renal disease later in life. These serious, adverse long-term consequences call for prudence with glucocorticoid treatment of human preterm infants and careful follow-up of young adults with a history of neonatal glucocorticoid treatment."