Aging Cells Make 'Signature' Molecules that Could Lead to New Treatments

Gray hairs and wrinkles might be visible signs of aging, but the signs we can’t see— such as the damage our cells accumulate—are just as telling according to a recent study.

Faulty components pile up in our cells as we grow older, but our bodies have mechanisms in place that stop damaged cells from making us sick. For example, cells stop making more of themselves if they’re too damaged and enter a state known as senescence in which they can’t divide.

Scientists have known that human cells that have undergone senescence produce a common set of molecules that are linked to age-related diseases, including heart disease, diabetes, and Alzheimer’s. But recently, researchers from the Buck Institute for Research on Aging were able to increase the list of these common factors from a few dozen to a few thousand. This ‘signature’ list of molecules gives scientists clues for what to target to combat diseases to help us live longer, healthier lives. The results were published in February in the journal PLOS Biology. 

The scientists in in this study used human cells from the lung and kidney.  They made these cells senescent in a lab dish to see what molecules they would make. 

Senescent lung and kidney cells made over a thousand molecules; only 150 were in common between them.

This indicates that an aging ‘signature’ will likely vary according to cell type and that identifying the molecules that distinguish our cells as ‘old’ might be more complex than previously thought.

Since the accumulation of senescent cells leads to diseases of aging, this ‘signature’  will be useful for measuring the efficacy of senolytic drugs which target senescent cells and have shown promise for treating many diseases that come with old age.

These drugs are currently not available, but Dr. Judith Campisi, professor at the Buck Institute for Research on Aging and corresponding author of the study, explained that the first senolytics are now in phase 2 clinical trials. “These drugs are on the horizon and they’re definitely going to happen,” she says.

Paradoxically, although the accumulation of senescent cells drives many of the diseases of aging, senescent cells can also prevent diseases. Senolytics will target disorders where senescent cells are common, but because these cells also have beneficial effects, Campisi says scientists have to be cautious in how they give them to patients. For example, she explained that senescent cells accumulate in the joints in patients with osteoarthritis and that the safer option would be to deliver senolytics directly to the joints, as opposed to taking them as a pill that would affect senescent cells in the whole body.

Campisi explains that however we use these drugs, we definitely don’t want to prevent senescence altogether. The question is whether we can reduce the bad effects of senescent cells while potentiating their beneficial effects. “I’m pretty optimistic that age-related diseases can be helped by these new drugs,” she says.