1. Get Moving
Our evolutionary ancestors needed to move to survive. We do, too. We all need to be pushing ourselves, physically, especially as we get older — and yet only 10 percent of people over the age of 65 do. The good news is that we don’t have to exercise for hours on end. People who run four to five miles a week (for most people, that’s an amount of exercise that can be done in less than 30 minutes every other day) reduce their chance of death from a heart attack by 40 percent and all-cause mortality by 45 percent. That’s a massive effect. You’ll know you are doing vigorous activity when it feels challenging. Your breathing should be deep and rapid, you should sweat and be unable to say more than a few words without pausing for breath. This is the hypoxic response, and it’s great for inducing just enough stress to activate your body’s defenses against aging without doing permanent harm.
I’m often asked about the potential of metformin, the diabetes medicine, or resveratrol, the red wine molecule, to inhibit the beneficial effects of exercise. You can read up about the science here and here, and a commentary by Peter Attia here. Firstly, let me say the jury is still out on this topic. There is no right answer and more studies are needed. But if I am pressed to summarize dozens of studies I’ve read and re-read on the topic, there are a few themes emerging:
Humans aren’t rodents: In rodent studies, resveratrol and metformin increase endurance, reduce inflammation, improve blood flow, and even seem to act synergistically with exercise. But in humans these same molecules show inhibitory effects on endurance, in the case of resveratrol, and on muscle building/hypertrophy, in the case of metformin.
The negative effects are not as huge as you might think: The study indicating endurance was blunted by resveratrol was not horrible, and subsequent studies backed it up. But the study was met with harsh scientific criticism from exercise experts. Quoting Smoglia and Blanchard, “Recent data do not provide evidence that resveratrol causes ‘mainly negative’ or ‘adverse’ effects on exercise training in humans...Such powerful wording suggests resveratrol actually counteracts the benefits of exercise training and is harmful, yet the results presented do not support such strong statements.” In the case of metformin, the effects of metformin on resistance training were statistically significant but not large, just a few percent, and the leg muscles weren’t statistically weaker.
The effects may still be beneficial. When I spoke to my colleague Nir Barzilai, who also worked on the metformin+exercise study, he pointed out the muscles of the subjects were, if anything, more powerful per mass. He was excited about the ability of metformin to seemingly blunt the damage and inflammation caused by exercise without affecting strength. Explanations for metformin’s blunting include the reduction of free-radical damage and inhibition of mTOR signaling, which is required for tissue growth (but may oppose longevity). A December 19 study provided another possible answer: metformin treatment slightly enhances “perceived exertion and whole-body stress which may provoke a lesser desire for physical activity in the metformin-treated patients.”
So what’s the take home? Until more data is available, I’ve taken to not taking resveratrol and metformin the days I exercise. Note that I’m not much of an athlete. I use my brain to make a living, so I aim to keep my white and grey matter functioning for the longest time possible, with my body providing essential oxygen and fuel. But if I were a professional athlete, even though these studies were on older subjects, I’d be less sanguine about taking these molecules, especially during training and competition, until more information becomes available.
https://lifespanbook.com/4-intervention ... 8-72616753
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