Senolytics, a Promising New Field of Medicine in the Treatment of Aging
It is becoming harder for the world at large to ignore the field of senolytics, the large number of research groups and companies working towards therapies that clear a fraction of senescent cells from aged tissues. Senescent cells accumulate in later life, likely because the immune system becomes less able to remove them promptly. Lingering senescent cells actively disrupt normal tissue function and provoke chronic inflammation, thus contributing to age-related degeneration. Scores of mouse studies conducted over the last decade demonstrate that senolytic treatments produce rapid, reliable reversal of many age-related conditions and extension of healthy life span. Most interestingly, the best of the early senolytic treatments, the dasatinib and quercetin combination, is cheap, readily available, and in human clinical trials with promising initial results. The opening decades of the 21st century are the start of a golden future, in which none of us will have to be as impacted by aging and age-related disease as our parents and grandparents were.
Cells eventually stop dividing and enter a "senescent" state in response to various forms of damage. The body removes most of them. But others linger like zombies. They aren't dead. But they can harm nearby cells like moldy fruit corrupting a fruit bowl. They accumulate in older bodies, which mounting evidence links to an array of age-related conditions such as dementia, cardiovascular disease, and osteoporosis. But scientists wonder: Can the zombie cell buildup be stopped? "The ability to understand aging - and the potential to intervene in the fundamental biology of aging - is truly the greatest opportunity we have had, maybe in history, to transform human health. Extending the span of healthy years impacts quality of life, public health, socioeconomics, the whole shebang."
"When you're young, your immune system is able to recognize these senescent cells and eliminate them. But when we start getting old ... the activity of our immune system also gets diminished, so we're losing the capacity to eliminate them." Senescent cells resist apoptosis, or programmed cell death, and characteristically get big and flat, with enlarged nuclei. They release a blend of molecules, some of which can trigger inflammation and harm other cells - and paradoxically can also stimulate the growth of malignant cells and fuel cancer.
Experimental drugs designed to selectively clear senescent cells have been dubbed "senolytics." In mice, they've been shown to be effective at delaying, preventing, or easing several age-related disorders. Possible benefits for people are just emerging. Researchers undertook a pilot study providing initial evidence that patients with a serious lung disease might be helped by pairing a chemotherapy drug with a plant pigment. Another pilot study found the same combination reduced the burden of senescent cells in the fat tissue of people with diabetic kidney disease. At least a dozen clinical trials with senolytics are now testing things like whether they can help control Alzheimer's progression, improve joint health in osteoarthritis, and improve skeletal health.
Scientists say serious work to improve human health could also bring fringe benefits - like reducing skin wrinkling. "I tell my lab that if we find a drug that clears the bad senescent cells and not the good ones and we cure Parkinson's disease and Alzheimer's and osteoporosis and macular degeneration, it would be wonderful. But if we cure wrinkles, we'll be rich, and I'll never have to write another grant. We know that senolytics work pretty well in mice. We're still really figuring out the basics with people."