You hit the nail on the head with the "centralized vs. decentralized" framing. It’s a design flaw in the system: once the engine (mitochondria) starts failing, it stops producing its own coolant (melatonin), which causes it to overheat and fail faster.
That vicious cycle is real, and the paper actually touches on exactly what you're asking about.
It cites a study (Suofu et al.) showing that melatonin synthesis is tightly linked to mitochondrial activity, specifically in the brain. When that production drops due to aging or disease, the system essentially eats itself.
But the good news is that the "manual override" seems to work. The review notes that exogenous melatonin didn't just act as an antioxidant; it actually restored respiratory physiology (specifically at Complex I and IV) and stimulated ATP production in neuronal mitochondria. It also fired up the SIRT3 pathway, which is basically the cleaning crew for mitochondrial stress.
So yes, the research suggests you can artificially break that loop. It’s not just acting as a hormone; it’s acting as a substitute for a broken metabolic part.
You hit the nail on the head with the "centralized vs. decentralized" framing. It’s a design flaw in the system: once the engine (mitochondria) starts failing, it stops producing its own coolant (melatonin), which causes it to overheat and fail faster.
That vicious cycle is real, and the paper actually touches on exactly what you're asking about.
It cites a study (Suofu et al.) showing that melatonin synthesis is tightly linked to mitochondrial activity, specifically in the brain. When that production drops due to aging or disease, the system essentially eats itself.
But the good news is that the "manual override" seems to work. The review notes that exogenous melatonin didn't just act as an antioxidant; it actually restored respiratory physiology (specifically at Complex I and IV) and stimulated ATP production in neuronal mitochondria. It also fired up the SIRT3 pathway, which is basically the cleaning crew for mitochondrial stress.
So yes, the research suggests you can artificially break that loop. It’s not just acting as a hormone; it’s acting as a substitute for a broken metabolic part.