One of the key issues we face is that while we know many compounds activate autophagy in some tissues, we don’t know where / what tissues, and how much. Also - while we know that autophagy is important and a good thing most of the time, we do not know the optimal doses or dose/response levels for all the different drugs and supplements that activate autophagy.
Tim Sergeant was one of the lead researchers on the the area of measuring autophagy in blood, they were the first group to do this I think. Sadly, not yet available in any clinics anywhere, only in the lab. Here are their details and paper:
Although autophagic flux can be measured in humans using the methodology detailed in , the ultimate goal must be to identify a biomarker of autophagic flux. An autophagy biomarker would permit two significant advancements: (i) retrospective characterisation of clini- cal specimen collections and biobanks and (ii) technological developments to measure autophagy easily in a clinical setting. Clinical assessment of a patient’s autophagy will allow practitioners to provide interventions or advice to change it to promote healthy ageing.
We need a lot of things for clinical translation. I don’t even know if a blood test will be a pan universal absolute target. Maybe there’s a magical Sirolimus dose/time curve (several blood tests) that is the golden key? Perhaps another blood marker tagged back to some “gate keeper” tissue/signal?
As an engineer (Peter Attia is also an engineer btw, he thinks like one), one of our mantras is “you cannot manage what you cannot measure”. Let alone know WHAT things to measure and WHY?
He laments about this with Rapamycin as an intervention, and agree this is where we are.
But I’m not deterred, will continue to try and hardness some benefit. There is no do over.
Carcinogenicity risk associated with tacrolimus use in kidney transplant recipients: a systematic review and meta-analysis (2022)
“Currently, tacrolimus is the preferred anti-rejection therapy for kidney transplant recipients due to its greater protection against acute rejections compared to cyclosporin. The results showed a significantly increased risk of overall malignancy associated with tacrolimus exposure compared to non-tacrolimus therapy [risk ratio (RR) =1.59,and especially with sirolimus (SRL) (RR =2.58. The data demonstrated that patients treated with tacrolimus had a higher risk of carcinogenicity compared to patients treated with SRL”
Too much mTOR inhibition, or triggering other negative feedback cancer loops? Depressing tumour suppressor genes? Dissociating mTOR2, as TOR1/TOR2 have a cross talk, feedback loop?