Exercise, VO2 max, and longevity | Mike Joyner, M.D

#350

Hate to be pedantic, but science is science. As is so frequent as to be almost unnoticeable, the headline makes claims the study does not deliver on.

1)Some biomarkers and functionality in the exercising twin more closely resembled a younger phenotype. That’s it. Period. The end. This does not prove in any way that this “delivers a younger body”. A younger body would mean all tissues in all respects. Including changes at a cellular level in all tissues, telomere length, elastin etc. Otherwise, no, it’s not a younger body. All they can show are what they showed - those specific markers are closer to younger phenotype, and furthermore that is not proof that even that is “younger”. If I undergo sophisticated plastic surgery to resemble a younger phenotype in an indistinguishable way - eliminate wrinkles, plump up collagen injections, color gray hair etc., this may have all the characteristics of “younger” without actually being younger.

2)The relevant outcome in the claims is lifespan and healthspan. This was not measured. So no claim can be made about it. Lifespan - both are alive, so the outcome is not there to make any claims about - what if the sedentary twin lives longer? As Matt Kaeberlein frequently points out “healthspan” is a tricky measure without formal definition. But it’s worse than that. I bet some folks thought it absurd to imagine the sedentary twin could live longer, because it seems intuitive and obvious that the nominally better healthspan (by some select measures) of the exercising twin should lead to a longer lifespan. The joke’s on them. Please examine the sex paradox. Men live shorter lives IN BETTER HEALTH. Women live longer, but spend more years in worse health, longer beyond the extra years they live compared to males. A man may croak at 80, being in poor health from 75, the woman may croak at 85 being in poor health from 70. Poor healthspan can still result in longer lifespan, so you cannot draw the conclusion “better healthspan equals longer lifespan”. I can show you experiments where voluntary exercise lead to shorter lifespans in strains of rats compared to non-exercising ones. Incidentally (and separately) that’s also true at the extreme end of CR (70%) where exercise actually shortens lifespan. But that’s even true of functionality (more in point 3 below), where CR’d animals are more frail, but live longer and healthier than their stronger, more vigorous and functional ad lib counterparts. Same btw. of castrated animals - not as strong, not as vigorous and functionally capable as intact ones, but live longer and in better health (see also in pets - longer lived, healthier “fixed”). Functionality, vigor and strength do not necessarily translate into either longer lifespan or healthspan (see below).

3)Measures that show superior physical functionality do not nessesarily translate into either health or longevity. Certainly that can be shown easily - bigger muscles, better functionality, bone mass, strength, power physical capability - bad health and short lives: bodybuilders. Before you start talking about steroids etc., stop - you are missing the point. The point is: like in this study - just having a collection of measures and biomarkers, tests of functionality does NOT mean better outcomes. Studies of twin cohorts where one group exercised the other did not and both lived just as long - what about that? This present study hasn’t even shown lifespan in many twins as others have, it’s a single shorter term pair - very weak sauce to make very big claims with no proof. The stupidity of this is really disappointing. You can only make claims about that which you have proven specifically. Here, they’ve proven remarkably little. Physical activity, whether with or without exercise is of the “good enough” variety. If you are an active non-exerciser (as the vast majority of supercentenarians have been - Jeanne Calment didn’t spend one day in a gym or formally “exercised”, lol), you can live as long and healthily as an exerciser (and who knows, maybe longer than the heavy exerciser). Being able to lift 200lbs the day before you die doesn’t mean better health or longevity vs being able to lift only 150 or 100. If your health is “good enough” for unhindered ADL, you are good to go - you can take all those “superior, greater” biomarkers in this study and stuff them, they won’t make a difference worth a hill of beans. If the sedentary twin is “good enough” in his ADL, he’s good to go, he might live just as long and successfully. Prove - prove - otherwise, exaggerated claims not proven mean nothing.

I could go on and on, but my point is - another study big on headline claims backed by nothing but speculation. Stop with the mechanical speculation and deilver outcomes. Nothing is “obvious” unless proven.

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#351

Lower body fat, lower blood pressure, lower cholesterol, lower glucose, better endurance and metabolic profile and lower BMI, etc., - these are not cosmetic differences — they are major predictors of reduced all‑cause mortality. So the exercising twin looked younger because their physiology was objectively younger. The younger appearance is not superficial — it’s a visible marker of internal resilience.Of course it’s not a guarantee that he will live longer than his other sibling - but it’s obvious that he lives much healthier life and has a good chance to outlive his sibling.

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#352

A summary and analysis:

Muscle health and performance in monozygotic twins with 30 years of discordant exercise habits

A pair of 52-year-old male monozygotic twins with 30 years of highly discordant exercise habits offers a rare window into the pure exposomal effects of chronic endurance training. One twin engaged in three decades of competitive endurance running and triathlons (Trained Twin, TT), while the other remained largely inactive (Untrained Twin, UT). The results are profound.

Endurance training yielded massive systemic metabolic benefits: the trained twin exhibited significantly lower resting heart rate, blood pressure, cholesterol, and visceral fat. However, the cost of this extreme endurance adaptation was a reduction in absolute muscle size, decreased voluntary isometric strength, and lower muscle “quality” (measured via ultrasound echo intensity) compared to his inactive, heavier brother. At the cellular level, the trained twin’s vastus lateralis muscle was fundamentally reprogrammed, expressing an extreme 94% slow-twitch (MHC I) fiber composition compared to the untrained twin’s 40%.

This divergence suggests the human cardiovascular and skeletal muscle systems possess far greater environmental plasticity than previous genetic heritability models indicated. While endurance training optimizes the systemic environment for cardiovascular longevity, the data highlights a practical biohacking gap: excessive aerobic volume without dedicated resistance training may compromise absolute mechanical strength and muscle quality as we age.

Context:

  • Institution: California State University, Fullerton; San Francisco State University; California State Polytechnic University.
  • Country: USA.
  • Journal: European Journal of Applied Physiology.
  • Impact Evaluation: The impact score of this journal is 2.7, evaluated against a typical high-end range of 0–60+ for top general science, therefore this is a Medium impact journal.

The Biohacker Analysis

Study Design Specifications

  • Type: Clinical In vivo (Case Study).
  • Subjects: Human, Monozygotic Twins, Male, N=2 (1 Trained Twin, 1 Untrained Twin).

Mechanistic Deep Dive

  • The exposome profoundly shifted nutrient-sensing and metabolic pathways. AMPK α1 and γ1 protein expression were significantly elevated in the trained twin, aligning with chronic endurance-induced AMPK activation. * Muscle fiber remodeling was extreme. The trained twin showed a near-complete conversion to slow-twitch dominance (94% MHC I), driven by downstream translational mechanisms rather than basal mRNA shifts, as MyHC 1 and 2a gene expression were similar between the twins.
  • Markers of mitochondrial biogenesis (TFAM) and angiogenesis (VEGFA, eNOS) mRNA were unexpectedly not elevated at baseline in the trained twin. This suggests a physiological ceiling or steady-state adaptation where chronic maintenance downregulates the acute mRNA transcription spikes typically seen in novel training.
  • Elevated PAX7 and IGF-1 variants (IGF-1Ea, MGF) in the trained twin indicate heightened satellite cell pools and continuous tissue repair. Conversely, elevated FN14 (a TWEAK receptor) hints at a pro-inflammatory or catabolic stress state in the muscle, which may explain the trained twin’s reduced absolute muscle size and strength.

Novelty

  • This is the longest controlled observation (30 years) of highly discordant exercise habits in genetically identical humans. It demonstrates that decades of specific training can push MHC I distribution to extreme limits, resulting in 55% more MHC I fibers than the untrained twin.

Critical Limitations

  • Translational Uncertainty: A sample size of N=2 prevents statistical power or broad population-level conclusions, making the data entirely observational. [Confidence: High]
  • Confounding Variables: The untrained twin reported consuming a caloric surplus over his estimated Total Daily Energy Expenditure compared to the trained twin. This surplus likely contributed independently to his 43.3% higher visceral adipose tissue. Furthermore, dietary data was collected via a 7-day mobile app recall, which notoriously limits data accuracy. [Confidence: High]
  • Methodological Weakness: Muscle quality was assessed using ultrasound echo intensity rather than the gold-standard magnetic resonance imaging (MRI). Additionally, biopsies were taken 48 hours post-testing, meaning acute performance test stress could have confounded resting mRNA levels. [Confidence: Medium]
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