38 replies to this topic

[johnhemming]

I don't think you have to worry overly much about oxidative issues -- as long as you are regularly inducing and enhancing AUTOPHAGY.

 

That is an interesting question.  Obviously Autophagy is helpful, but I am not aware of any evidence that indicates that it prevents any concerns about Oxidative stress.

[sensei]

That is an interesting question. Obviously Autophagy is helpful, but I am not aware of any evidence that indicates that it prevents any concerns about Oxidative stress.

Autophagy cleans up the result of oxidative stress - damaged organelles, protein waste etc. A special type of autophagy, (mitophagy) cleans up mitochondria damaged by ROS.

Dysfunction and deficiency of Autophagy is specifically cited in the pathophysiology of inflammatory aging, and specifically with respect to poor remyelination in MS.

Autophagy is the CLEANUP MECHANISM the body uses to ameliorate oxidative damage, accordingly ROS triggers autophagy and mitophagy.

From the entropy model of aging: Autophagy reduces entropy in the body by reducing the disorder in cells through cleanup of non-functional and damaged cell parts, and/or recycling of components.

It should be noted that ascorbate is REQUIRED for AUTOPHAGY to function optimally. Without enough C, lysosomal action and efficiency is reduced.

A point mutation that leads to increased aging.

Edited by sensei, 07 February 2022 - 07:38 PM.

[johnhemming]

The question, however, is one as to how quickly new mitochondria get damaged by further Oxidative stress.  I am not aware of any answers to this level of detail.

[Zarathrustra]

Thanks for the informative responses. I hope responders will bear with me as I comment chronologically.

 

John Hemmings 12:47 07Feb22: Thanks for that. I’m going to assume that with my low inflammation and exercise my NAD levels are probably good.

I’m more unsure about the model that tinkering with the cellular level, as plausible as the theory is, necessarily translates to an optimised body system. I already have, for me, evidence that what correlates well for by CV doesn’t for my CKD.

 

Sensei 15:58 07Feb22: How does one measure Autophagy? From what I can glean, it is either a very specialised lab-derived metric, or an assumed effect of fasting (that is, not directly measured). Without an easy way to detect it, maybe my mainly vegetarian diet, exercise, sleep, etc are doing the job.

Whilst CRP may not be the best metric for inflammation, I don’t know of any other easily available metric. Would there not be a correlation between CRP and those you think are better anyway? Perhaps CRP is a good enough indicator? In my case it is only one of many biometrics I use to assess my health/illness of the three degenerative illness I’m prey to (CV, CKD, and cancer).

 

Both: Whilst I will continue to try anything that promises to reduce or reverse ageing, those I have tried to date (fisetin, melatonin, MitoQ, Niacel, etc) haven’t correlated too well with the more attested metrics I use. For me, the macro trumps the micro – am I frail, can I walk well, am I mentally OK (I had the fortunate experience the other day in being the subject of a memory assessment research project – taking two hours – and luckily, I’m OK), do my bones break when I fall (not), are my longs OK, my hand-grip, etc. That said, I’m trying hard to lie long enough to benefit from any proven anti-ageing programmes that come along.

 

[sensei]

Whilst CRP may not be the best metric for inflammation, I don’t know of any other easily available metric.

I checked, there are blood tests for the serum level of IL-1B, IL-6, IL-17, IL-18 , etc.

These are among the inflammatory/pro-inflammatory cytokines.

IL-17, in particular, is the target of most of the new anti-psoriatic monoclonal antibody treatments and anti-rheumatic treatments.

[sensei]

@ Z

Have you researched beta-hydroxybutyrate?

BHB is a ketone produced in the body during ketosis that inhibits the NLRP3 inflammasome, turning off or down the IL-X inflammation parade.

Of interest is that BHB seems to be protective against CVD.

I personally, have just started to supplement with it.

[johnhemming]

I take small amounts of KE4.  (5ml some days)

https://shop.ketoneaid.com/

 

This AIUI metabolises to BHB.  It has a mild GABAergic effect.

 

https://en.wikipedia...xogenous_ketone

 

It tastes a bit odd, but is mildly helpful for sleep.  I have not measured any other benefits.

[Zarathrustra]

Hi Sensei. Thanks for that.

 

I’ve now looked further into IL-1B, IL-17,etc.

 

I could not find any lab offering a blood test for this, at least not to the general public in the UK.

 

However, when I checked some research papers (sample below), it seems there is a fair correlation between CRP and these other inflammation markers. So on that basis, I’m happy to continue to use CRP as my inflammation marker.

 

There was a correlation between IL-1b and sTNF-RI. IL-6 and IL-1b correlated with CRP levels

IL-6 levels showed a positive correlation with hs-CRP (Spearman rank = 0.52, P < 0.001)

Correlation between serum IL-6 and CRP. | Download Scientific Diagram (researchgate.net)

 

With regards butyrate, I have tried a couple of versions of this (one called Gundry Bio complete, the other TauBiotic Butyrate). On balance it does seem helpful, correlating with lower resting HR, lower PNN50, and Total Cholesterol. Having said that, it correlates with less deep sleep.

 

[johnhemming]

The Ketones are mildly GABAergic so it should help getting to sleep at least in small quantities.  What impact they have on sleep more generally and types of sleep I have not seen any reports on.