Is Low LDL Bad For The Epigenetic Pace of Aging?

[Mike Lustgarten]

 

[Mike Lustgarten]

Attempting To Slow The Epigenetic Pace Of Aging (13-Test Analysis)

 

[drewab]

I really appreciate the longer video here Michael. It is a bit wild to think that no foods/nutrients are significantly correlated with DunedinPACE. Nice work getting to 11th or 12th on the Rejuvenation Olympics leaderboard (even if that isn't your overall goal). How many names have been submitted? I heard it's about 4000 at this point, which would make your results pretty impressive!

I don't understand why a higher LDL would result in slower aging. Intuitively this just doesn't make sense to me and it doesn't square up with the Ornish/Esselstyn studies that have reversed heart disease and had patients with very low LDL's. I know that this is obviously different than aging and all-cause, mortality, I'm just trying to square this up in my basic brain. I'll be curious to see how this shakes out with more tests. Are calories associated with DunedinPACE in your data?

I commend you for your detailed testing of SFA, LDL, and Dunedin pace without "blowing up the system" as you put it. 

 

 

Edited April 14 by drewab

[Mike Lustgarten]

Thanks drewab. I'm not sure about the why, but it looks like this effect may not be specific to me: 

"After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05)."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925395/

[Alex K Chen]

You really should differentiate sdLDL vs the other types. sdLDL is uniquely bad, other types are barely different from HDL. It's easy to get lipid subfractions, the technology is not that expensive, and all LDL measurements are confounded by fraction that's "good" vs "bad" LDL. Your results might be especially good, but we don't know until we see your lipid subfractions

https://www.questdiagnostics.com/our-company/actions-insights/2017/ldl-subfractionation-testing-can-help-id-patient-risk

If your LDL is of the unusually good subtype, good for you, but potentially misleading for others.

Edited April 14 by InquilineKea

[Ron Put]

7 hours ago, InquilineKea said:

You really should differentiate sdLDL vs the other types. sdLDL is uniquely bad, other types are barely different from HDL.

Not necessarily. It's a rapidly fading theory. Dense LDL particles are associated with those with more severe CVD, but by themselves do not appear to have predictive value.

Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic (oup.com)

 

[IgorF]

IMHO the situation with abnormally low LDLs originates from the approach of contextless data sciencing and creates unwanted confusion due to this.

For myself I use this model to understand it (or "understand", for obvious reasons of complexity).

There is a flux of materia into a sophisticated transforming machinery called liver. There is a processing capacity with optimal range of operation let's say 40-90% of approximated saturation point. With such a flux the size of exported cargoes will be determined by many factors but most of them will fluctuate close to mean values observable in the population. If we will artificially increase the flux at the input then the system will leak the extra to some other paths (if they exist and to the extent of their saturation) or will start to export lower sized cargoes, just to get rid of overload because there is no housing for it (yes, there is some and fatty liver is a sign of saturation of this backup mechanism). So actually it is pretty imaginable within the queing theory used in engineering.

There is a rare exceptional share for small abnormal cargoes - genetically determined, these people will produce abnormal particles within a normal flux values but my intuitive feeling is that they account for minuscule shares of a percent.

In other words - for most of the people the start of production of smaller particles is a redflag about unwanted input overload that itself is a sign that a lot of problems will come in other areas - the network of queues goes deoptimized and no one could predict where the things will start to break. No magic pill or any kind of mimicking or biohacking will help, there is no way to mimic normal traffic in a congested network, there should be incoming rate limit implemented until it will become too late and parts of the mechanism will be deformed.

From this perspective it does not make a big difference if smaller particles are more atherogenous themselves, this adds to the bad prognosys but should be of concern especially for those with rare unfortunate genetics, 99.9% of other people should rethink their energy balances.

Br,

Igor

 

Edited April 15 by IgorF

[Ron Put]

12 hours ago, IgorF said:

In other words - for most of the people the start of production of smaller particles is a redflag about unwanted input overload

It sounds plausible, yep.

[Alex K Chen]

What do you mean by "smaller particles"?

LDL particles range from 18–25 nanometers in size, while HDL particles are only 5–12 nanometers

sdLDL is determined by NMR as particles with sizes from 18.0 to 20.5 nm [34, 35].

VLDL is even larger than LDL

Overnutrition increases flux of the larger particles - the triglyceride carriers like (VLDL/chylomicrons). VLDL will always form a tiny fraction of all total cholesterol, but overnutrition increases the larger LDL particles way more than the smaller HDL ones.

Edited April 25 by Alex K Chen

[IgorF]

The idea is - thinking about flux and seeing the liver as a production facility, with a quantitative angles regarding processing and storing capacities.

There is surely a detection mechanism (perhaps many of them) that spins up all the complicated machinery to orchestrate the output. When detector will rise the "high watermark" (that could also be rised for prolonged period) then the cargo output part of the machinery will prepare and spill out cargoes as soon/often as possible, thus sometimes exporting an unoptimally packed ones - these famous small dense ldls. In other words - the effect is not to make all the cargoes smaller but to make more cargoes and there will be considerably bigger share of smalls amongst them.

In non enginerring language the same idea is - do not allow the detector to "see" the abundance, but do it is a natural, not "hacking" way, e.g.:

Quote

Expression of small LDL has a strong environmental component, and treatment is often the least expensive and includes reduction of excess body fat, avoidance of simple carbohydrates in the diet, exercise, niacin, fibric acid derivatives and omega-3 fish oil. Specific patient subgroups may benefit from sdLDL-C analysis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025822/

Of all the things mentioned I personally think only the first two are really matters and have a long-term effect, starting from the word excercise is almost useless for the goal. The same for sat/unsat comparisons that brings some difference and so on, energy overdoing will diminish any tricks because it acts on all 37thrillion of body cells and there is neither exist nor will ever be engineered way to do something with it, switching off some part of machinery in one place will force the flux to dig the holes in another areas.

 

Br,

Igor

[Alex K Chen]

Mileage also shows large LDL particles really decrease mortality

[Mike41]

https://pmc.ncbi.nlm.nih.gov/articles/PMC10982736/
 

Looks like moderation in all things! Not to much and not to little!

Among primary prevention-type patients aged 50–89 years without diabetes and not on statin therapy, the lowest risk for long-term mortality appears to exist in the wide LDL-C range of 100–189 mg/dL, which is much higher than current recommendations. For counselling these patients, minimal consideration should be given to LDL-C concentration

Edited November 5 by Mike41

[Ron Put]

On 11/5/2024 at 11:10 AM, Mike41 said:

Among primary prevention-type patients aged 50–89 years

These are all high-risk patients, so I guess that while such high LDL-c values may be optimal for their condition, it doesn't mean it's so for healthy individuals.

[Alex K Chen]

They're *older* so we don't know their LDL when younger, but high-risk people are at way higher risk of actual heart attacks/arteriosclerosis..

[Mike41]

What about the confounder wherein low ldl levels occur with illnesses. I thought that was part of the problem with these studies. Many issues like malnutrition, cancer etc can cause lower ldl levels which would associate it with higher mortality but not be a cause

[Saul]

I agree Mike.

[Mike41]

 

[Mike Lustgarten]

Spot on. LDL is low in youth, peaks in midlife, and then declines towards the end of life...

DunedinPACE was trained on a young group (< 50y), so why is low LDL associated with a faster epigenetic speed of aging? Did those with low LDL have underlying health conditions?