Between the damage from the oxygen you breathe, the food you eat, ionizing radiation, plus the normal damage from cell division, all that can drive aging—not just by causing cancer but also through cellular degeneration.
What would you say is one of the biggest mysteries of aging research?
Why do organisms with remarkable genetic similarity have sometimes remarkable differences in life span?
We know that for the most part, many of the processes that go on in the human body also go on in yeast and mice. Yet, yeast live a few days, a mouse lives about three years, and people live for decades. We really do not know what evolution has done to take basically the same genes and produce different life spans.
Is that where the naked mole rat comes in?
Yes. The mystery shows up even in species that are mouselike. The naked mole rat is more related to the mouse than to us—it looks like a mouse. And yet it lives for 30 years, or 10 times longer than a regular mouse. On top of all that, it has signs of oxidative damage that exceeds that of the mouse.
Now there are three ideas that scientists have come up with to try to explain why naked mole rats live so long: Maybe oxidative damage doesn't cause aging. Maybe naked mole rats are evolutionary oddities. And then my personal favorite, maybe it's not oxidative damage that is the problem but how the cell responds to the damage. But that's all speculative.
Any hope for treatments?
We really don't know whether it will be possible to substantially extend human life span. But we do think we will learn how to extend human health span, or the number of years that older people can live in relatively good health.
One of the protective mechanisms that we have evolved against cancer is called cell senescence. When a cell is damaged it either dies in a process called apoptosis or it simply stops dividing. That's cell senescence.
A few years ago, we learned that when cells opt to senesce they don't die. They persist. They increase with age. And they secrete inflammatory cytokines. So they can produce low level of chronic inflammation throughout the body with no obvious pathogen, and we think that is one of the drivers of aging. This is an example of an evolutionary trade-off. If you don't have the senescence mechanism, you die early of cancer. But if you do have this mechanism, you die later and miserably.
Do I think if I had a drug tomorrow that could kill senescent cells, it would make a human live for 5,000 years? No, I don't. But it might help attack several problems of aging—like Parkinson's disease or Alzheimer's disease—that involve a lot of inflammation. The idea would be not to treat one disease at a time, but to get at the underlying processes, like inflammation.