paulrhjtimmers

This is the correct answer.

Generally better, but the answer is a little more nuanced.

We had access to data describing how DNA influences iron levels, and how DNA influences years of healthy life. This showed that the same DNA variations that change your levels of iron in the blood also change how many years you spend in good health.

Now, these genetic effects are relatively small, so we can confidently say that people who carry genes which cause them to have slightly lower iron levels (i.e. one standard deviation) than the population average will be healthier, on average.

However, extrapolating that further can be dangerous - for example, anyone with iron levels three standard deviations lower will not be three times healthier, they'd have no iron in their blood and be dead.

If this were an observational study, I'd completely agree. In that case, it could be that people who eat better diets and do exercise happen to have lower iron levels, but it is the diet and exercise that makes them live longer, not the iron.

Our study actually used a different method! We found that the genes that raise iron levels in the blood also have an effect on how long and healthy we live. Since you don't get to choose the genes you are born with, this method is more robust to confounding. It's not perfect by any means, but it does provide reasonably robust evidence for a causal role of iron rather than just a correlation. Still, we would like to verify this in follow-up experiments, possibly using animal models.

Great and important question! All data we used was corrected for sex. In other words, we knew the effect of DNA on iron levels, and the effect of DNA on lifespan/healthspan, regardless of the person's sex.

Great comment! For the iron - ageing link, we used two pieces of data: the effect of DNA on blood iron levels, and the effect of DNA on how long and healthy you live. We found the mutation that causes hereditary haemochromatosis had a large effect on early death (as expected). However, other genetic variations that increased blood iron levels also had a proportional effect on early death. So it looks like it is higher iron levels, not just haemochromatosis, that may accelerate the rate of ageing.

Hi there, I'm one of the study authors. Iron plays many roles and is needed for your body to function correctly, but we found people who had higher blood iron levels because of their genes were getting diseases earlier in life and had a shorter lifespan, on average.