Senolytics: Living healthier for longer with a new class of drugs

Dec 3, 2018

Cellular senescence -- when stress causes cells to change their function in the body -- is common and sometimes harmful in older adults, but scientists are working on medications that can help kill them.

Senolytics drugs can selectively induce death of senescent cells. Dr. Judith Campisi, a researcher and professor of biogerontology at the Buck Institute for Research on Aging, joins us today on “Take Care” to explain this new class of drugs and their potential use. She said senolytic drugs could be one way to combat the aging process.

Campisi, who is also co-editor-in-chief of the Aging Journal, said senescence often occurs as people age due to age-related stresses that serve as physiological signals to the cells to change their function. The resulting senescent cells emit molecules that promote tissue repair, but when accumulated, can have a degenerative effect.

“The reason why it’s important to understand that there’s the good side and the bad side is because it’s very important in understanding aging to understand the evolutionary context in which what we recognize as aging has evolved,” Campisi said.

The accumulation of senescent cells is gradual, accelerating in the middle of one’s lifespan, though senescent cells never rise to majority levels, according to Campisi. These cells can be deleterious, leading to the unwanted side effects of aging.

“They can drive and cause those diseases and manifestations of aging that we recognize as being undesirable,” Campisi said.

"Each senescent cell secretes a whole slew of molecules that can have profound effects on neighboring cells."

Those effects are why there is an effort to kill off senescent cells, which is where senolytics come in. According to Campisi, this new class of drugs selectively cause senescent cells to die based on their gene expression pattern, which makes them vulnerable to protein changes. The drugs tweak proteins in a way that cause senescent cells to die, but leave most other cells unaffected. Remaining cells will eat those dead ones for nutrients.

“Each senescent cell secretes a whole slew of molecules that can have profound effects on neighboring cells…And by eliminating those cells, you alleviate that influence of senescent cells,” Campisi said.

But it is an evolutionary balancing act, Campisi said. She said there has not been any indication so far that using senolytics to rebalance those scales causes harm, but current trials of senolytics are only in beginning stages of of safety testing, so it is still early.

“We’re cautiously optimistic that we understand when we have to be cautious when using these drugs,” Campisi said. “But it’s pretty exciting.”

Some current senolytics were initially designed as anti-cancer drugs, Campisi said, but once they were used to combat senescence, the strategy changed slightly.

“When you’re treating cancer, you have to kill every cancer cell. If you don’t do that, the cancer will come back,” Campisi said. “We know, from the mouse model, that’s not true for most age-related diseases.”

Doctors do not have to kill every senescent cell, just about 80 percent, Campisi said. As a result, the drug doses can be lower and the treatment period shorter.

Though the science in promising, Campisi said the focus is not to help people live longer, but to live a healthy life for as long as possible.

“The new concept in aging research is extending health and not necessarily lifespan,” Campisi said.