A medication used by millions (including off-label usage for “longevity” purposes) may alter the fundamental pathways responsible for exercise adaptation. This episode reviews new 2025 data showing reduced improvements in vascular insulin sensitivity, aerobic capacity, and glucose regulation when the medication is paired with structured training. We look at prior evidence of blunted mitochondrial respiration and diminished hypertrophy, along with 2020 transcriptomic findings that paint a more nuanced picture.

The goal: clarify when this medication interferes with exercise-driven improvements in muscle, mitochondria, and vascular function, and when it may support resilience during aging.

00:00 – Intro
00:48 – The Rise of a “Longevity” Medication
01:31 – New Clinical Data Challenges Expectations
03:34 – Earlier Trials Showed the Same Pattern
05:05 – Resolving the Apparent Contradiction
07:10 – Who Should, and Shouldn’t, Use This Medication

PMID: 30548390
PMID: 31557380
PMID: 33071237
PMID: 37928155