In a zoo, a mouse and a naked mole rat can live side by side. Both are about the size of a palm, yet the mouse will grow old in three years, while the mole rat lives to thirty. The difference is not in how fast they chew or run, but in how quickly their cells burn through the safety margin stored in their mitochondria.
Mitochondria work like an hourglass. The grains of sand inside them are lesions in mitochondrial DNA that pile up with age. The supply of sand is the metabolic reserve, that is, the power a cell keeps on hand beyond its basic needs. As long as the reserve is large, the cell copes with stress. Once the grains fill the hourglass, the reserve is spent, and aging begins.
Researchers gathered data on 379 mammal species: body mass, lifespan, the composition of mitochondrial DNA, and temperature. It turned out that three numbers explain nearly 70% of the variation in how long a species lives. The larger the animal, the bigger its reserve. The higher the share of sturdy bases in its DNA, the less often it breaks. And every extra degree of warmth speeds up the buildup of defects.
It used to be unclear why different tissues in the same body age in sync even though they renew at different rates. Now it looks as though all cells share a common source of trouble: mitochondrial DNA accumulates damage, and internal resistance in the respiratory chain rises. A cell cannot make enough new molecules, because its energy goes into fighting that resistance.
Today this knowledge could help in the search for drugs aimed not at individual diseases of old age, but at the wear-and-tear process itself. If the conductivity of the respiratory chain can be restored, the hourglass can be turned over. But for now it is only a theory, tested against numbers rather than living cells.
The naked mole-rat lives up to 30 years, even though its size matches that of a mouse, which lives 3 years. The secret lies in its low body temperature (about 32°C) and high GC% in mitochondrial DNA, which slows the accumulation of damage.
In H. G. Wells's The Time Machine, the Eloi and the Morlocks represent species with different lifespans, echoing the idea of tuning metabolic reserve through evolution.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.