Mangan is becoming more convinced that excess iron may be one of the most important drivers of aging:
In aging, we see a progressive increase in inflammation, oxidative stress, mitochondrial dysfunction, and a loss of autophagy intensity. These processes normally rise and fall together, so that an improvement or deterioration in one means the same for the others. One reason I’ve emphasized autophagy so much on this blog is because simple interventions like fasting and certain supplements can readily increase autophagy to youthful levels, leading to an improvement in all aspects of aging.
Could iron be the cause of these important aspects of aging? I believe that they could.
Consider insulin resistance, which increases with age and is strongly related to many disease states, including heart disease, cancer, and sarcopenia (1), not to mention diabetes. Insulin resistance features elevated levels of inflammation, oxidative stress, mitochondrial dysfunction, and decreased autophagy, making it an archetype of aging.
In insulin resistance, serum ferritin, the most important measure of body iron status, is strongly correlated with glucose tolerance.(2) The correlation coefficient was 0.73, i.e. high. Ferritin also correlated with blood pressure.
In men, a high serum ferritin, >300, was associated with a 5-fold increased risk of being diagnosed with diabetes.(3)
Many of these studies control for body mass index (BMI), but consider that visceral and subcutaneous fat both also correlate with ferritin.(4)
Metformin is a drug commonly used to treat diabetes, and in contrast to other diabetic drugs, actually extends lifespan in lab animals.(5) There have been suggestions that diabetics treated with metformin may actually live longer than non-diabetics without metformin, leading to the idea that metformin is a true anti-aging drug. Some people are now taking metformin for the purpose of lifespan extension.
How does metformin work? In a cell culture model in which metformin protects against damage from chemotherapy, it was found that the mechanism is restoration of iron homeostasis.(6) Without going too deep into the biochemistry, the body keeps iron under tight control, and metformin restores that control.
Metformin is also effective on non-alcoholic fatty liver, and the mechanism may be decreased iron absorption.(7)
You know, medicine is not an exact science, but we are learning all the time.
The ultimate cause of aging could be that human evolution has selected lifespans according to available environmental resources and reproductive pressures. We develop clogged arteries and diabetes from eating certain crappy foods because our bodies are getting signaled that there’s a shortage of nutrient dense foods, and to correct for it we need to activate auto-destruct to preserve the greater population at-large.
The classic study is the female octopus, which normally dies shortly after giving birth. When her optic gland is removed, she stays alive and can reproduce again, suggesting that is the source of a chemical signal telling her to check out.
I’d say the cause of aging is that we shrivel up and die. Why? We are bags of blood, which is wet, in air which is less wet. Thus, we dry out and die. I’ve thought this since I read Methuselah’s Children forty years ago. We should do a skunk works proof of concept on some old folks home — just refill the oldies until they balloon back up from their present, shriveled state. Millions would volunteer.
Best case, geriatrics would become what acne doctoring is now — the patient never dies, and he never gets well — so he’s always paying you!
I am not convinced about fasting. Is there any evidence? There are several kinds of people that fast, many for religious reasons, so the signal should exist.