A city power plant is running itself into the ground, but the city doesn't know it yet. Lights are on in its homes, the streets are noisy, and only the engineers notice that the turbines are spinning more slowly and voltage is dropping in the wires. This is what an aging brain looks like: the neurons are alive, but their internal power plants, the mitochondria, are already losing capacity.
Scientists took mice with a defective gene that accelerates the shortening of telomeres, the protective caps on the ends of chromosomes. By five months, activity of mitochondrial respiratory complexes in the hippocampus, the memory area, had dropped by about 20%. It's as if the power plant were putting out a fifth less energy, yet the city kept running.
So why don't the neurons die right away? Because they have a reserve. Mitochondria accumulate damage and produce more aggressive molecules, reactive oxygen species, but the cells still hold on. Only in certain zones, such as the subiculum, does the number of neurons fall by a few percent. The energy deficit comes later: in nine-month-old mice, levels of ATP, the cell's main energy currency, decline.
Previously it was unclear how telomere aging affects neuronal energetics and why the brain becomes vulnerable long before cells die. Now it's clear: mitochondrial dysfunction comes first, while energy starvation and neuron loss develop later and only in certain regions. It's as if the power plant first ran intermittently, and then the lights went out in some neighborhoods.
Even today, these findings can be used to search for early biomarkers of brain aging and to test drugs that support mitochondria. If we can find a way to stimulate the compensatory mechanisms that keep ATP levels up in young mice, we may learn to push back the energy crisis in the aging brain. And then the city we call the brain will keep its lights on longer.
The brain makes up only about 2% of body mass but consumes roughly 20% of all oxygen. A 20% drop in mitochondrial activity in such an organ is equivalent to mild hypoxia.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.