Antioxidants and Autophagy

Mitochondrial reaction to ROS (“free radicals”) is part of how we gain increased work capacity through exercise.

Some guy recently showed a 30% increase in mouse lifespan with some mitochondrial-ROS-protective drug (which you can’t obtain yet).  This would probably come at the cost of decreased adaptation to exercise.

Most antioxidants do a terrible job of protecting the mitochondria but somehow prevent the ROS generated in exercise from triggering the exercise benefit - worst of all possible outcomes.  This may explain why a recent study of antioxidants in humans found them to be harmful (esp. Vit E, but also others) to overall lifespan.

There are several antioxidants which protect mitochondria, all of which are avaliable as supplements:

1. CoQ10

2. Chlorophyllin

3. Carnitine and Lipoic Acid

4. Quercetin

None of which extend life notably in healthy mice. e.g. see this null result for CoQ10:

So there’s nothing really great available.  Resveratrol, which is among other things an antioxidant, has some weak evidence of providing a net longevity benefit:

In the only positive human trial, extremely high doses (3–5 g) of resveratrol in a proprietary formulation have been necessary to significantly lower blood sugar.[2] Despite mainstream press alleging resveratrol’s anti-aging effects,[3] there is little present scientific basis for the application of these claims to mammals

Red grapes have the most resveratrol; blueberries have 1/10th the amount (blueberries have some other compound, thought to be brain-protective)

Autophagy removes cell components - including ROS-damaged proteins and organelles - by engulfing and digesting them, producing wastes and recycled nutrients. … Upregulating autophagy [has] extraordinarily wide-ranging benefits. Interventions that extend healthy lifespan in animal models include calorie restriction, resveratrol, spermidine, and rapamycin, and in each operates, at least in part, through autophagy. Upregulating autophagy has positive effects in models of several specific neurodegenerative diseases, too … antioxidants inhibit basal autophagy and block the induction of autophagy by calorie restriction and other means. Because this effect inhibits the central mechanism of cell repair, it helps explain why dietary antioxidants have failed to deliver their expected benefits to health and longevity.” I would have said it has more to do with failing to target mitochondria, given the benefits demonstrated by mitochondrially targeted antioxidants. As Drexler notes, however, there’s research to back up the antioxidant-autophagy link, which may have some relation to earlier research showing antioxidant supplementation to interfere with the processes of hormesis, and thus block beneficial effects of mild stress such as exercise. 

Autophagy is good (if you want to live long).  Antioxidants also generally interfere with that.

Rapamycin is immunosuppresive and so not of practical interest (unless you want to live in a bubble).

Spermadine (exact mechanism unknown) increases autophagy in cultured cells, and lifespan in yeast, nematodes, and flies.