Senolytics: A new class of drugs with the potential to slow the aging process
It's a cruel irony that when we're young we want to be older, but when we're older we want to be younger. While few would advocate research into ways to make kids grow up faster, there are plenty of efforts underway looking to forestall the rigors of age. The latest cause for hope in this area comes in the form of a new class of drugs called senolytics, which have been shown to dramatically slow the aging process in animal models.
As we age, senescent cells, which are cells that have stopped dividing, build up in our bodies and accelerate the aging process. Knowing that killing off these cells increases the amount of time mice are free of disease (known as the "healthspan"), scientists from The Scripps Research Institute (TSRI), Mayo Clinic and other institutions set out to find treatments that could do this in humans without damaging other cells.
They found that senescent cells were similar to cancer cells in that they boasted an increased expression of so called pro-survival networks that help them resist apoptosis, or programmed cell death. This finding allowed them to narrow the search for potential drug candidates and hone in on two available compounds. The first was dasatinib, a cancer drug marketed under the name Sprycel, and quercetin, a natural compound sold as a supplement that acts as an antihistamine and anti-inflammatory.
Tests in cell cultures showed that these two compounds did selectively induce death of senescent cells, targeting different cells. The dasatinib eliminated senescent human fat cell progenitors, while quercetin was found to be most effective in eliminating senescent human endothelial cells and mouse bone marrow stem cells. However, the best overall results were achieved with a combination of the two compounds.
Moving out of the Petri dish, old mice given a single dose of the drugs exhibited improved cardiovascular function within five days, with mice weakened by radiation therapy used for cancer treatment showing improved exercise capacity. The improvement was found to last for at least seven months after the drugs were administered. The healthspan was also extended in mice models with accelerated aging that were periodically administered the drugs, with age-related symptoms of spine degeneration and osteoporosis delayed.
The researchers point out that it is possible that long-term treatment of both compounds may have side effects, but they remain hopeful of the potential of their findings.
"Senescence is involved in a number of diseases and pathologies so there could be any number of applications for these and similar compounds," says TSRI Professor Paul Robbins, PhD. "Also, we anticipate that treatment with senolytic drugs to clear damaged cells would be infrequent, reducing the chance of side effects."
The team's research appears in the journal Aging Cell.
Source: The Scripps Research Institute