Acylcarnitines Increase During Aging, And Are Associated With Poor Health

#1

Here’s a summary of the key points from the YouTube video “Acylcarnitines Increase During Aging, And Are Associated With Poor Health.” Unfortunately, I’m not able to access YouTube directly to watch the video, but I reviewed the detailed companion blog post that outlines its content—and trust it accurately reflects the video’s main messages (Michael Lustgarten).

Main Takeaways

1. Acylcarnitines Rise with Age

  • Plasma levels of several acylcarnitines—including long-chain, medium-chain, and odd-chain species—tend to increase as individuals age, particularly in older adults. This trend appears linked to mitochondrial dysfunction and incomplete fatty acid β-oxidation (Michael Lustgarten, Aging-US).

2. Connections to Health Decline and Sarcopenia

  • Elevated levels of specific metabolites—such as C0 (free carnitine), C4 (butyrylcarnitine), C6, C18:1-OH, and kynurenine (KYN)—are associated with poor muscle function and sarcopenia (age-related muscle loss) in older Taiwanese adults (Michael Lustgarten).

3. Biomarker Potential

  • Using age, body mass index (BMI), blood urea nitrogen (BUN), KYN, and normalized butyrylcarnitine (C4/Cr), the video’s study showed strong predictive power:
    • Low Physical Function (LPF): AUC ≈ 0.766
    • Sarcopenia (S): AUC ≈ 0.787
    • Severe Sarcopenia (SS): AUC ≈ 0.919
      This suggests a promising metabolic signature for monitoring progression from early functional decline to severe muscle loss (Michael Lustgarten).

4. Mechanistic Insights

  • Kynurenine (KYN): Often elevated in inflammatory or immune-activated states, KYN levels were particularly associated with severe sarcopenia, suggesting a link between immune signaling, fatigue mechanisms, and muscle deterioration (Michael Lustgarten).
  • Acylcarnitines: Elevated levels reflect impaired mitochondrial function—notably incomplete fatty acid breakdown—and are tied to metabolic dysregulation (e.g., insulin resistance, cardiovascular disease), as well as age-related decline (Michael Lustgarten, Aging-US).

5. Study Strengths and Limitations

  • Strengths:
    • Combines metabolic profiling with age, BMI, and other clinical data to identify potential biomarkers of sarcopenia.
    • Addresses both muscle mass and functional capability.
  • Limitations:
    • Cross-sectional design: Limits ability to infer causation.
    • Gender and demographic composition, as well as lifestyle factors, may influence generalizability.
    • Additional, longitudinal studies are needed to confirm these biomarkers’ predictive value across diverse populations (Michael Lustgarten).

Summary Table

Key Point Insight
Acylcarnitines & Kynurenine Levels rise with age; linked to poor muscle function and sarcopenia.
Predictive Biomarkers Age, BMI, BUN, KYN, and C4/Cr offer strong risk differentiation (AUC up to 0.919).
Biological Mechanisms Impaired mitochondrial β-oxidation (acylcarnitines) and inflammation (KYN).
Clinical Relevance Potential early detection tools for sarcopenia progression.
Study Context Cross-sectional, Taiwanese cohort; broader validation needed.

Let me know if you’d like to dig deeper into any aspect—be it the metabolic mechanisms, how these biomarkers might be applied in practice, or how this fits into broader aging research!

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#2

Real Time Cell Metabolic Analysis

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#3

Exercise has to be the best way to improve mitochondrial function, or at least amount of mitochondria or density. In Inigo San Millan’s experience, exercising at maximum fat oxidation (around 2 mmol/L lactate), which he calls Zone 2 is best for this.

The proof is in the pudding. Without better and more mitochondria there would be no fast marathon runners or Tour de France winners. I’m pretty sure muscle biopsies on these athletes show this as well.

Couldn’t resting and active lactate levels also be a test of mitochondrial function? The latter being dependent on work output (peter attia calls it w/kg on an exercise bike for example at 2 mmol/L lactate sustained).

#4

Exercise can definitely improve mitochondria number and function, but the question is the dose. For example, excessive exercise is bad for mitochondria function (https://www.sciencedirect.com/science/article/pii/S1550413121001029), so how would one know if their dose is appropriate?

That’s where testing comes in, whether through the acylcarnitine sum, or plasma lactate, which is another good marker.

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#5

Interesting video. A new marker!

I understand there is an interplay between mitochondrial health and metabolic health (metabolic flexibility; ability to burn fat and rapidly shift between burning fat and glucose). Maybe it’s the same thing at a high level but there is a cause and effect. A person cannot build mitochondrial capacity by focusing on burning fat (only eating fat, for example). First build mitochondria vis endurance exercise (zone 1& 2 — talking pace and below), and then metabolic flexibility will be possible regardless of diet (within reason).

Does anyone know the science here? @ConquerAging ?

#6

This is a really good post by Chris Masterjohn:

I wish I could say I understand what he’s talking about. It looked to me like something John Hemming would understand and benefit from. Unfortunately only available today to the public. Use it or lose it.

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#7

Unfortunately, even their cheapest model, Agilent Seahorse XF HS Mini AnalyzerList Price: 68,611.00 USD, but you can get a used one on eBay for $34,000.
It would be neat to have one to monitor what was happening when we take various supplements.

#8

You do not purchase a unit, most would not have the resources

You can “rent use” of a unit at a lab, they will charge you for the testing kit and time.

You can run the test your{if you know how] or you can pay additional time for a technician to run the test for you

The information/data collected is yours

Example:, one of several placed available.

Search

“Seahorse shared resources”

You will locate many places

You have a “skunk works” available, and you not even realize it.

1 Like
#9

Funny. I moved this to the top of my list yesterday. I listened for 15 minutes.

I heard some thing like, “may I mumble dogfish to the banana tree?”

I moved on.

I like Masterjohn. But some of his stuff is for a niche of his audience — people with unusual health problems that have resisted traditional or other reliable solutions.

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#10

Are you asking knowing the science on mitochondria metabolism?

If that is your question, the major researcher in that field is Professor Nick Lane (PhD, FRSB, FLS) is Professor of Evolutionary Biochemistry in the Department of Genetics, Evolution and Environment at University College London.

https://nick-lane.net/

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#11

I don’t think it’s meant to be understood.

“If you cannot explain something in simple terms, you don’t understand it” Richard Feynman.

#12

Thanks. I found a podcast he did with Sean Carrol that I’ll check out. I’ll also revisit Dr Zone 2 himself, Dr San Milan

#13

LONG CHAIN

#14

What can acylcarnitines tell us about health and disease? (virtual event)

Here’s a summary of the key points from the video:

Overview

  • The video is a virtual event featuring three presentations that delve into the biochemistry and metabolomics of acylcarnitines, particularly examining their role in health and disease, and how plasma concentrations of long-chain acylcarnitines act as insightful biomarkers.(YouTube)

Acylcarnitines: What They Are

  • Acylcarnitines are esters formed by conjugating fatty acids (acyl groups) with L-carnitine.
  • They function as transporters of acyl groups into the mitochondrial matrix, enabling β-oxidation and energy production.(DIVA Portal, biocrates life sciences ag)

Clinical and Biomarker Roles

  1. Neonatal Screening

    • Acylcarnitines have long been established as diagnostic biomarkers for inborn errors of fatty acid oxidation, making them indispensable in newborn screening programs.(DIVA Portal, gimjournal.org)

  2. Beyond Neonates: Broad Clinical Relevance

    • Research shows that acylcarnitine levels can reflect broader metabolic dysfunctions across various disease contexts, including:

      • Diabetes
      • Cardiovascular disease
      • Cancer
      • Sepsis
      • Drug-induced toxicity (e.g., from valproic acid, cisplatin)(PMC, DIVA Portal)

Acylcarnitines in Aging and Disease Risk

  • Levels of certain acylcarnitines increase with age, and this rise is particularly notable in long-chain species.

  • These changes correlate with mitochondrial dysfunction, inflammation, and age-related diseases like cardiovascular disorders, diabetes, and neurodegenerative conditions.(Aging-US)

  • Elevated acylcarnitines are linked to:

    • Higher cardiovascular mortality risk, serving as markers for future disease events.(PMC, ScienceDirect)
    • Impaired physical function, especially in older adults—higher medium- and long-chain acylcarnitines are associated with an increased risk of functional limitations.(Nature)

Summary Table

Aspect Key Insight
Biochemical Role Facilitates mitochondrial fatty acid β-oxidation
Traditional Use Neonatal screening for inborn metabolic disorders
Expanded Biomarker Use Diseases such as diabetes, cardiovascular and neurodegenerative conditions
Aging Correlation Levels increase with aging; linked to inflammation and mitochondrial dysfunction
Predictive Value Associated with increased disease and functional decline risk

Final Thoughts

Acylcarnitines are much more than metabolic intermediates—they are powerful biomarkers that span across lifespan and disease states. From newborn screening to predicting disease risk and functional decline in older adults, these molecules are proving invaluable in precision medicine and metabolomics research.

Let me know if you’d like a deeper dive into any of the presentations or specific disease contexts covered in the virtual event!

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