Killing off cells that refuse to die on their own will be powerful for antiaging

The anti-aging biotechnology space has really started to heat up recently. Clearing old zombie cells in mice has been shown to restore fitness, fur density and kidney function. It has also improved lung disease and even mended damaged cartilage. And in a 2016 study, it seemed to extend the lifespan of normally aging mice.
Biotechnology and pharmaceutical companies are keen to test drugs — known as senolytics — that kill senescent cells in the hope of rolling back, or at least forestalling, the ravages of age. Unity Biotechnology in San Francisco, California, co-founded by van Deursen, plans to conduct multiple clinical trials over the next two-and-a-half years, treating people with osteoarthritis, eye diseases and pulmonary diseases. At Mayo, gerontologist James Kirkland, who took part in the 2011 study, is cautiously beginning a handful of small, proof-of-concept trials that pit senolytic drugs against a range of age-related ailments.
This is a summary of the Megan Scudellari Nature article. Nature – To stay young, kill zombie cells
The US Food and Drug Administration has not labelled aging as a condition in need of treatment.
Unity’s president, Ned David, there will be a massive push to develop treatments and to better understand the fundamental process of aging if there is any hint of success in the upcoming trials. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York City. “I think senolytics are drugs that could come soon and be effective in the elderly now, even in the next few years.”
Senescent cells are slightly different in each tissue. They secrete different cytokines, express different extracellular proteins and use different tactics to avoid death. That incredible variety has made it a challenge for labs to detect and visualize senescent cells. “There is nothing definitive about a senescent cell. Nothing. Period,” says Campisi.
In fact, even the defining feature of a senescent cell — that it does not divide — is not written in stone. After chemotherapy, for example, cells take up to two weeks to become senescent, before reverting at some later point to a proliferating, cancerous state, says Hayley McDaid, a pharmacologist at Albert Einstein College of Medicine. In support of that idea, a large collaboration of researchers found this year that removing senescent cells right after chemotherapy, in mouse models for skin and breast cancer, makes the cancer less likely to spread.
The lack of universal features makes it hard to take inventory of senescent cells. Researchers have to use a large panel of markers to search for them in tissue, making the work laborious and expensive, says van Deursen. A universal marker for senescence would make the job much easier — but researchers know of no specific protein to label, or process to identify. “My money would be on us never finding a senescent-specific marker,” Campisi adds. “I would bet a good bottle of wine on that.”
Earlier this year, however, one group did develop a way to count these cells in tissue. Valery Krizhanovsky and his colleagues at the Weizmann Institute of Science in Rehovot, Israel, stained tissues for molecular markers of senescence and imaged them to analyse the number of senescent cells in tumours and aged tissues from mice11. “There were quite a few more cells than I actually thought that we would find,” says Krizhanovsky. In young mice, no more than 1% of cells in any given organ were senescent. In two-year-old mice, however, up to 20% of cells were senescent in some organs.
But there’s a silver lining to these elusive twilight cells: they might be hard to find, but they’re easy to kill.
Researchers identified six signaling pathways that prevent cell death, which senescent cells activate to survive.
In early 2015, the team identified the first senolytics: an FDA-approved chemotherapy drug, dasatinib, which eliminates human fat-cell progenitors that have turned senescent; and a plant-derived health-food supplement, quercetin, which targets senescent human endothelial cells, among other cell types. The combination of the two — which work better together than apart — alleviates a range of age-related disorders in mice.
14 senolytics have been described in the literature, including small molecules, antibodies and, in March this year, a peptide that activates a cell-death pathway and can restore lustrous hair and physical fitness to aging mice.
Unity maintains a large atlas documenting which senescent cells are associated with which disease; any weaknesses unique to given kinds of cell, and how to exploit those flaws; and the chemistry required to build the right drug for a particular tissue.
There’s no need to kill every senescent cell in a tissue: mouse studies suggest that dispatching most of them is enough to make a difference. Finally, senolytic drugs will clear only senescent cells that are already present — they won’t prevent the formation of such cells in the future, which means that senescence can continue to perform its original tumor-suppressing role in the body.
Killing off senescent cells in normally aging mice delayed the deterioration of organs associated with aging, including the kidney and heart. It extended the animals’ median lifespan by about 25%.
Side effects include delays in wound healing.