In modern medicine, aging is sometimes considered a disease just like any other. Since people unsurprisingly want to live longer, healthier lives, the question becomes whether it’s possible to delay aging. The answer: Kill all the sickly old cells!
Depending upon whether you’re an optimist or a pessimist, that either sounds brilliantly ingenious or like crazy talk, yet distilled to its essence, that’s what a recent paper in Nature found. As the Mayo researchers so aptly state, “Advanced age is the main risk factor for most chronic diseases and functional deficits in humans,” so the logical conclusion to that line of thinking is that if you can stop the adverse effects of aging, you should be able to stop disease. Simple, right? In reality, not quite so simple.
Cellular senescence – that’s what it’s all about
Before looking at the details of the Nature paper, it’s worthwhile to ask the question – what is aging really? Individual cells don’t live forever, but the body remains functional through the continued division of certain designated cells, ensuring a constant supply. Uninhibited cell division is very undesirable (read: creates tumors), so therefore a system of cellular “aging,” called senescence, is in place to constrain cell growth. In many cases, there’s a limit to how many times a given cell can divide before further cell division is stopped. Older cells are more likely to have DNA that is damaged or unable to replicate correctly, and this causes a stress-response to kick in, of which one of several outcomes is senescence.
The exact signals that cause a cell to undergo senescence – as opposed to cell death (apoptosis) – in response to stress remain a mystery. Setting aside the details of exactly how they came to be there, the fact remains that senescent cells accumulate in aging tissues, and secrete a variety of chemicals. Their effect on neighboring tissue – be it good, bad or neutral – was unknown, and this was the starting point for the paper’s research.
Selectively killing senescent cells
In order to determine whether senescent cells cause aging, or simply are an effect, the Mayo researchers wanted to selectively remove all senescent cells. By brilliant genetic engineering, they managed to make a mouse model where they could administer a drug killing cells expressing a marker called p16-INK4A, which is found only in senescent cells. The drug could be injected into the mice at any stage in their lives, and all senescent cells would then undergo cell death, leaving the rest unharmed.
The results were fascinating. With lifelong treatment with the senescent cell-clearing drug, the incidence of age-related pathologies, such as cataracts, a lowered exercise capacity and loss of healthy fat in the skin decreased. When the drug was given to older mice that already showed signs of aging, fully developed cataracts didn’t reverse, but muscle diameter and exercise capacity improved, and the mice became fitter again. Moreover, they were unable to find any overt negative side effects. In other words, the accumulation of senescent cells was clearly detrimental, and removing them did the mice a world of good.
Bring on the anti-aging drugs!
Although the average lifespan of a mouse is relatively short, researchers still chose to do the experiment in a fast-aging breed of mice to save time. Consequently, they were unable to determine the effect on lifespan. The research proves the concept that clearing senescent cells (or at least preventing their effects) might be a useful therapeutic tool to treat or slow the progression of age-related disease. But don’t expect a miraculous anti-aging drug on the market any time soon.
It’s obviously not an option to genetically engineer humans to kill senescent cells in response to a drug like the mice did. Nevertheless, these findings bring the science of aging one step closer to understanding age-related disease. If they’re supported by further evidence, there’s hope that it would be possible to keep people in good health for longer. Immortality might sound appealing to some, but for now, a longer health span is a more realistic goal, and still pretty awesome!
Written by Hanna Sofie Ellingsen at CERG.