At the end of the meeting, Martin Brand and Stuart Kim led a group discussion about the free radical theory of aging. Martin began the discussion by pointing out that “after 50 years, you would expect a theory to accumulate enough evidence to convince us that it’s true or false – but the fact that we’re still discussing it today means that hasn’t happened.” I’m paraphrasing slightly, but that’s the general idea.
Martin Brand (who doesn’t, by the way, adhere to this theory) started by summarizing the evidence in favor of FRTA:
- “50 million Frenchmen can’t be wrong” (i.e., there are lots of correlative experiments)
- SOD2 knockout is bad
- catalase overexpression is good
Stuart rejoined with some contradicting evidence:
- Superoxide dismutase protects against oxidative stress but has little effect on lifespan in mice
- Deletion of mitochondrial SOD extends lifespan in C. elegans
- High oxidative damage levels in the longest-living rodent, the naked mole-rat.
To the last of which, others answered:
- The naked mole rat isn’t suffering from a global increase in oxidative damage – rather, there are a small number of proteins with increased damage, which may represent antioxidant proteins protecting the rest of the cell
- There’s no evidence that naked mole rats increase damage with age, which is a more relevant metric
The first two pieces of Stuart’s contradicting evidence were more difficult to challenge. Some ideas:
- Overexpressing an antioxidant enzyme in the wrong subcellular compartment wouldn’t be predicted to have any effect on lifespan
Martin also asked questions about whether FRTA is even falsifiable, and lamented the absence of an alternative clear, single-sentence “singular” theory of aging.
No final resolution but on the balance it seems like the theory is on the ropes, as we’ve discussed here before.