#65

I think it is similar to the hypergrowth concept for mTOR. Our sympathetic nervous system gets turned on too much in modern life, and gets “stuck” in the on position or just gets stronger while the parasympathetic system does not get stronger (unless we are meditating) or gets weaker (if we are not sleeping well). The system gets out of balance, and now we are not good at either responding to threats or recovering from life stress.

Learning to meditate is hard. HRV biofeedback is a nice bridge to learning to meditate effectively, and it might actually do some good in the meantime.

I just finished my interview with Marco Altini PhD of HRV4Training. Stay tuned for the episode. But I’ve already started using HRV biofeedback.

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#66

Perhaps oddly, but I am a creature of habit and I take HRV readings twice a day and don’t find that much variation day to day. Fortunately, my readings are consistent with the 25-34 year old age group. I only choose these times because they are convenient for me.

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#67

Very good article. Thanks. As opposed to your stable HRV, my HRV is highly variable, during the day as your graph shows, but also between days for readings done at the same time with the same procedures. If I worked out hard, didn’t sleep well, didn’t feel well…my HRV is 50% of my good days.

#68

I get values from Polar and Fitbit. I only record the morning. There is a very obvious affect from alcohol and also a potential effect from the question as to the balance between sympathetic and parasympathetic systems (which can be impacted by melatonin usage).

Going back from today as examples. The larger figure is almost always Polar/Elite.

47/21 54/34 53 52/12 (insufficient pantethine) 53/25 43/43 54/26 44/18 60/29 50/36 60/31 50/49 60/35 50/33.

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#69

Here, on this YT video, Richard A Miller from NIA ITP talks about “Aging rate indicators” from mice:

In short:

  1. low CRP
  2. low TGF-beta
  3. high CIT
  4. low mTorC1
  5. high mTorC2
  6. 10 different biomarkers
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#70

I just stumbled upon this list that Troy Delaney has pulled together from what Peter Attia has mentioned in his various podcasts, etc.

Just one more data point for people to consider when they develop their list of personal biomarkers to track (and functional tests also)…

RECOMMENDED LABS, TESTS & METRICS

Markers for Healthspan: Cognitive Scores, Hormone Levels, VO2 Max & Emotional Health Podcast Clip (2:07)

Recommended Labs

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Details on the Recommended Labs

Things to Measure One Time:

  • Lp(a) (Lipoprotein A): Phenotype – Peter recommends knowing Mass and Particle number
  • APOE Genotype: Risk for Alzheimer’s/greater risk from head injury. People have a mix of 2, 3, and 4 (one from each parent)
    • Having 2 ApoE4 alleles can increase risk of AD (Alzheimer’s Disease) by 10-20x. Peter argues that this is definitely worth checking as you can in fact prevent Alzheimer’s disease

Things to test at least once a year:

  1. Saúde Cardiovascular
  2. APOB: APOB is the main protein found in LDL cholesterol. It is the total concentration of LDL and v-LDL which are the big atherogenic particles. Peter thinks a cutoff of less than 90 milligrams per deciliter is good, less than 70, you’re doing great, and less than 50 is pretty optimal and close to perfect. If you want to live to 100, keep it below 30.
  3. Small LDL-P: Peter wants this to be below 500 nmol/L or ~ 25th percentile (20 mg/dl)
  4. Trigs: Most responsive to diet changes (lower carbs); reference is < 150 mg/dL (< 1.7 mmol/L) but Peter wants this < 100 mg/dL (< 1.13 mmol/L); trigs should be lower than HDL.
  5. LDL synthesis: The most preset/not variable
    * Better predictive markers than LDL-C (despite C being the more common test)
  6. VLDL Cholesterol: Non-HDL cholesterol and subtract LDL cholesterol below 15mg/dl
    * Endocrinology: Adult and Pediatric (Seventh Edition)
  7. Total cholesterol is basically useless, HDL is minimally valuable
    * Peter likes to see: TG < HDL-C (when measured in mg/dL)
  8. IGF-1 (Growth Hormone surrogate) – strong driver of cancer; likely that cycling between low and high levels of IGF-1 is optimal;

Fasting can dramatically lower IGF-1

  1. OGTT (oral glucose tolerance test): Metabolic health, try to get it with insulin measurements

    1. Goals = Fasting glucose below 90, 1 hour post prandial <130, 2 hour glucose below 100

  3. Keto diet people will have very high levels after a challenge (low before), but this isn’t accurate

  4. Fasting glucose: Only directionally interesting. This varies a lot during the day, difference from 90 or 105 is more about your cortisol level than metabolic issues

  5. Peter uses a Continuous Glucose Monitor (CGM). He doesn’t like the Abbot Freestyle Libre (not accurate enough), has a test version of the Dexcom G6 which is much better. It has a tiny needle, no calibration needed and can connect with your phone
    * A month of CGM data is > an OGTT test to Peter
    * On CGM, “I like to see my patients with a mean glucose below 100 mg/dL, a glucose variability below 15 mg/dL, and, as noted above, no excursions of glucose above 140 mg/dL.”

  6. DEXA: Look at three things: Appendicular lean mass index (ALMI) and fat-free mass index (FFMI). “I [Peter] aim for my ALMI to be in at least the 90th percentile, if not above the 97th percentile as I age. The data are unequivocal: people live longer, better lives with an ALMI above the 75th percentile.”

  7. He also looks at:
    1. Segmental BMD
    2. VAT
    3. FMI Total

  8. ALT (alanine aminotransferase): Liver health

    • < 20 U/L and (reference upper limit: 42-44) and AST 40 but Peter wants patients below 20

    • Best test to see if your liver has issues (side note: ALT elevations are a signal that you should stop taking a new medication – many potential new drugs are stopped if they elevate ALT)

    • Don’t simply accept it if your Dr. tells you your levels are “normal” as those levels have drifted up over time as the average person has gotten less healthy)

    • Fatty Liver/NASH will be the leading driver of liver transplant in the future in US

Honorable mentions: Hcy, hs-CRP, fibrinogen, Lp-PLA2, ADMA, SDMA, Estradiol (E2) – these levels keep going up on average in American men; knowing your family history is important.

Family History: More important than doing a whole genome sequence. But behavior matters (e.g. if your grandma smoked and you don’t)

Longevity Markers: Longevity genes include APOE, Lp(a) and then the below:

  • Heart Disease: The younger you are, the more blood tests can tell you about your risk of cardiovascular disease, older people need to rely more on scans (e.g. CT angiograms)
  • Omega Index Plus Test: Likes to see EPA/DHA index above 8.5; OmegaQuant offers a good at-home test (use code TROY for 10% off). This is the same test used in Peter’s concierge medical program.
  • Inflammation: Fibrinogen, CRP, oxLDL, and oxPL
    • hsCRP: < 1 mg/L (labs say below 2)
    • oxLDL: < 40 U/L (labs say < 60 U/L)
  • Endothelial Health: Insulin sensitivity, homosystine, ADMA, SDMA
  • Cancer: Blood gives up the least insight, until liquid biopsy tests become accurate (company like Grail)
    • Most cancers are somatic mutations not germ line mutations so knowing your genotype doesn’t help much with a few exceptions (e.g. BRCA and Lynch)
    • As a result, you can focus on inflammation markers and metabolic health
  • Alzheimer’s Disease: APOE tells you low/medium/high risk and long with risk driven by the same drivers of heart disease, metabolic component, and toxins which we can’t understand/track the least
    • TOMM40: A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer’s disease (Roses et al., 2010)

Longevity Fitness Metrics (per Joe Rogan interview and Huberman interview)

  • Grip strength – Dead hang test 2x/week – Goal is 2 minutes for men at age of 40 and 1.5 minutes for women (discounted by decade)
  • Eccentric strength – step down from a 16″ block and take more than 3 seconds
  • Strict air squat hold at 90 degrees, 2 minutes for men and women at age 40
  • Hold 50% of your bodyweight and do a certain number of box step-ups
  • Farmers carry – Male carry body weight for 2 minutes, females 75% of your body weight
  • VO2 Max
  • Ankle mobility

Below are the extensive tests you would get if you joined Biograph, Peter’s concierge medical practice:

Source: https://troydelaney.com/peter-attia/#elementor-toc__heading-anchor-6

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Blood tests people like in general
Easy Hacks Guide Targeting Different Biomarkers (BMI, apoB, blood pressure, HbA1c, eGFR, etc)
#71

Excellent information! Exactly what I’ve been looking into. I’ll investigate testing for each one and try to decide what meets the standard for being essential and also worth the cost. The total could easily get too expensive. I’ve already added a number of things for my next blood test and picked up some reasonable home testing equipment.
And Biograph…
https://en.wikipedia.org/wiki/Fuhgeddaboudit

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#72

Yes - everyone is going to have a different cost/benefit tradeoff in terms of which tests and biomarkers are best to track given their medical history, concerns, and budgets.

The functional biomarkers are easier and lower cost… so perhaps relevant to everyone.

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#73

I find that labs tend to offer a standard package which always includes some basic biomarkers, but also varies as to other ones.

As I am doing tests weekly I take the view to stick mainly to the standard package unless I am doing a specific tests for say Mn,Se,Cu,Li etc.

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#74

This seems like a very valuable test to understand metabolic health and for our optimization of longevity?

Has any done it? Any thought? Does below seems like a good way to do this:

3hr GTT (4 Specimens),3hr Glucose Tolerance, Glucose Tolerance Test, 4 Specimens

With Quest / ULTA

https://testdirectory.questdiagnostics.com/test/test-detail/10559/glucose-tolerance-test-4-specimens?cc=MASTER

With Life Extention

https://www.lifeextension.com/lab-testing/itemlc090365/glucose-tolerance-test-4-specimens-blood-test#

Paired with Insulin during the same window via something like this

https://testdirectory.questdiagnostics.com/test/test-detail/6694/insulin-response-to-glucose-4-specimens?cc=MASTER

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#75

@AnUser @L_H this seems to be in the intersection of what you both have argued is important - have you done any blood work like this? Any thoughts on it?

Does anyone else have any thoughts on it?

Ulta has it for instance:

1 Like
#76

@L_H @anuser
This one also seems to help measure things you both have mentioned.

https://bostonheartdiagnostics.com/test/oxpl-apob-c-2/

Anyone have thoughts on it?

Seems like normal Quest/Ulta, LabCorp, etc don’t have it? Anyone see anything similar or easier way to get it than via BostonHeart (via e.g. Rupa)?

1 Like
#77

It’s from older podcasts as well. oxLDL is useless according to Thomas Dayspring, OxPL-apoB useful for those with high lp(a):

If someone says something, even Peter Attia from five years ago or today, I must verify it first myself.

5 Likes
#78

This one does seem like a very important risks factor…?

See review below.

Has anyone done this test?

Oxidized phospholipids in cardiovascular disease | Nature Reviews Cardiology

Abstract

Prolonged or excessive exposure to oxidized phospholipids (OxPLs) generates chronic inflammation. OxPLs are present in atherosclerotic lesions and can be detected in plasma on apolipoprotein B (apoB)-containing lipoproteins. When initially conceptualized, OxPL–apoB measurement in plasma was expected to reflect the concentration of minimally oxidized LDL, but, surprisingly, it correlated more strongly with plasma lipoprotein(a) (Lp(a)) levels. Indeed, experimental and clinical studies show that Lp(a) particles carry the largest fraction of OxPLs among apoB-containing lipoproteins. Plasma OxPL–apoB levels provide diagnostic information on the presence and extent of atherosclerosis and improve the prognostication of peripheral artery disease and first and recurrent myocardial infarction and stroke. The addition of OxPL–apoB measurements to traditional cardiovascular risk factors improves risk reclassification, particularly in patients in intermediate risk categories, for whom improving decision-making is most impactful. Moreover, plasma OxPL–apoB levels predict cardiovascular events with similar or greater accuracy than plasma Lp(a) levels, probably because this measurement reflects both the genetics of elevated Lp(a) levels and the generalized or localized oxidation that modifies apoB-containing lipoproteins and leads to inflammation. Plasma OxPL–apoB levels are reduced by Lp(a)-lowering therapy with antisense oligonucleotides and by lipoprotein apheresis, niacin therapy and bariatric surgery. In this Review, we discuss the role of role OxPLs in the pathophysiology of atherosclerosis and Lp(a) atherogenicity, and the use of OxPL–apoB measurement for improving prognosis, risk reclassification and therapeutic interventions.

Key points

  • Phosphocholine-containing oxidized phospholipids (OxPLs) induce chronic inflammation, including in atherosclerotic lesions, and can be detected in plasma on apolipoprotein B-100 (apoB-100)-containing lipoproteins.
  • A method has been developed to quantify OxPLs on a normalized amount of apoB-100 (OxPL–apoB), so that the measurement is independent of plasma apoB-100 and LDL cholesterol levels.
  • Lipoprotein(a) (Lp(a)) particles carry the largest fraction of OxPLs among apoB-containing lipoproteins; the OxPLs are bound covalently to apolipoprotein(a) and are free in the lipid phase of the associated LDL-like particle.
  • Plasma OxPL–apoB levels predict the presence and extent of anatomical atherosclerotic cardiovascular disease, and elevated levels are associated with disease in multiple arterial beds; measurement of OxPL–apoB improves prognostication of peripheral artery disease, as well as incident and recurrent myocardial infarction and stroke, and improves risk reclassification, particularly in patients in intermediate risk categories, for whom improving decision-making is most impactful.
  • Plasma OxPL–apoB levels are reduced by treatment with antisense oligonucleotides aimed at reducing Lp(a) production and by lipoprotein apheresis, niacin therapy and bariatric surgery.
  • Plasma OxPL–apoB levels predict cardiovascular events with a potency similar to or greater than that of plasma Lp(a) levels, probably because OxPL–apoB levels reflect the levels of the most atherogenic and pro-inflammatory Lp(a) and apoB-100-containing particles.

https://www.nature.com/articles/s41569-023-00937-4

2 Likes
#79

Yes, I suspect this will be the future of cvd prevention. I haven’t had the test but am looking for a provider in the UK. I’m particularly interested in the impact of the various ldl interventions. My guess would be that statins and then bempedoic acid would have a big benefit impact.

Oxidized low-density lipoprotein associates with cardiovascular disease by a vicious cycle of atherosclerosis and inflammation: A systematic review and meta-analysis - PMC.

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#80

Some fitness / functional biomarkers to target?

Here: Good Fitness Goals at Age 50 (Couzins)

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#81

Admittedly not a great take on functional biomarkers, but here it is just because its out there at a popular newspaper, from the Wall Street Journal:

Are You Fit for Your Age? Test Yourself With These Exercises

Measuring your cardiovascular fitness, strength and balance can give a read on how well you’re aging

Having an idea of your so-called fitness age matters. You can slow various declines in health through relatively minor changes, say academics and health professionals. Cardiovascular changes, for example, have been shown to add years to your life.

The first step is to track your fitness benchmarks in areas such as aerobic capacity and muscular endurance. Then, you should aim to keep them in an optimal range to help manage your aging, says Dr. Randall Espinoza, associate director at the UCLA Longevity Center. (You can try some sample tests below.)

While there is no universally agreed-upon way to measure fitness age, a true road map to longevityshould also consider diet, consistent and adequate sleep, and maintaining social ties.

Full article: Are You Fit for Your Age? Test Yourself With These Exercises (WSJ)

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#82

Attia has a new company focused on individualized exercise programs for longevity…

This article discusses the approach and some biomarkers they use:

The 10 Squared squad are like fitness precogs in Minority Report, connecting clues in the present to prevent a bad event before it happens in the future. They will triangulate the results from the 30 drills I do for stability, strength, and cardio; factor in my body composition from a DEXA scan; then prescribe a fitness plan to power me for the next five decades. That’s not a typo; this program is not 7-Minute Abs! or Great Shape in 4 Weeks! It’s a training blueprint for your whole life.

The Author’s Key Results & 10 Squared’s Target Numbers

DEXA SCAN: Lean mass (aka muscle)

RESULT: 97th Percentile

GOAL: 75th percentile or above

DEXA SCAN: Body fat

RESULT: 50th percentile

GOAL: 25th percentile (for body fat, lower is better) (I need to go from 23% fat to 18% or lower.)

CARDIO: Based on VO2 max

RESULT: 43.8 High for a 50 to 59-year-old

GOAL: 53+ Elite for 30- to 39-year-olds

STRENGTH: Using a hand grip strength device

RESULT: Right: 55.1 kg, Left: 49.2 kg, 85th percentile

GOAL: 75th percentile or above (Less than 30 kg is considered frail.)

STABILITY: Single-leg Romberg test: stand on one leg eyes closed

RESULT: Right: Not stable after 5 seconds, Left: Not stable after 2 seconds

GOAL: 20 seconds without foot or lower-leg movement, swaying, or arm waving

Peter Attia's 10 Squared: The Three Pillars of Forever Fitness

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#83

AST and ALT are not very good for assessing liver health. New info for me. Here is MedCram talking about liver function and markers.

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#84

I like these functional fitness biomarkers (as a quick way to see how fit you are) that were highlighted in the Peter Diamandis PDF: Peter Diamandis Longevity Protocol: Weekly 6mg Rapamycin + 100 mg Doxycycline - #90 by RapAdmin

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More details:

https://medium.com/@acuregan/fitness-50-at-age-100-a6f30ebd3067

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