3 replies to this topic

[sub7]

Title of the Paper is this
Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders

 

https://science.scie...nt/371/6526/265

 

I don't think there are any glutaminolysis inhibitors we can get our hands on -or are there?

[Mind]

Whether or not this is a promising senolytic approach depends upon what they used to inhibit KGA-dependent glutaminolysis in mice (need access to the full paper). Maybe it won't work in people. Could be harmful in people. Glutamine is an essential amino acid. Disrupting metabolism associated with glutamine could have longer term negative effects. Short-term (just to kill a few senescent cells), maybe it would be okay.

[Turnbuckle]

This paper covers a number of senolytics, including one that inhibits glucose transport--

 

4.15.1. Phloretin as Toxic Compound in Cancer

Phloretin is known to inhibit glucose transporter (GLUT) 2, a process which results in the induction of apoptosis in cells with high metabolic requirement, as shown in human liver cancer cells HepG2 treated with 200 μM phloretin [258]. At the dose of 10 mg/kg, phloretin was found to exert antitumor effects in immune deficiency mice carrying a HepG2 xenograft [258].

 

4.15.3. Phloretin as Potential Senolytic

Phloretin at 50 μM was found to specifically reduce the viability of therapy-induced senescent lymphoma cells [45]. These cells were also shown to be sensitive to another blocker of glucose transporters, cytochalasin B, thus suggesting that the mechanism by which phloretin induces cell death in senescent cells is related to their increased metabolic requirement.

 

 

 

 

[sub7]

 

This paper covers a number of senolytics, including one that inhibits glucose transport--

 

 

 

 

interesting

I was under the impression it wasn't orally bioavailable but at least in rats, it appears that it is

 

 

Oral administration of phloretin to diabetic rats for 45 days significantly reverted back the levels of glucose, insulin, lipid peroxidation, enzymatic and non-enzymatic antioxidants to near normal. The present findings suggest that phloretin treatment in diabetes exerts a protective effect by attenuating hyperglycemia mediated oxidative stress and improve the antioxidant activities. So, the phloretin may be used as food supplements for the treatment of diabetes.

 

from:
https://www.oatext.c...s.php#gsc.tab=0

 

The bigger question is whether the amount of phloretin that needs to be taken to have senolytic effects is safe.

 

Turnbuckle,

Do you consider any type of senolytic worthwhile? (I am talking about inducing senolysis through means other than what has already been discussed as part of your mitochondrial manipulation efforts)