When cells in the body experience stress or damage, they sometimes respond by becoming senescent, entering a state of arrest until they are cleared away by immune cells.
As people age, however, through mechanisms that aren’t entirely clear but that possibly stem from inefficient clearance by aging immune cells, cells accumulate. No longer functional, they cease to contribute in a positive way to the tissues they comprise.
More problematically, senescent cells don’t just die off and do nothing—they cause damage. Releasing a blend of molecules called the senescence-associated secretory phenotype (SASP), they promote inflammation and can impair surrounding tissue. As they accumulate, they can contribute to arthritis, osteoporosis, glaucoma, Parkinson’s disease, Alzheimer’s disease, and other age-related afflictions.
To better understand the mechanisms behind this process, Chisaka Kuehnemann, a postdoctoral scholar at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA), studies cell death, looking at the ways in which senescent cells might be cleared out instead of staying in the body and causing harm.
“Understanding the cellular mechanisms underlying senescence allows us to target vulnerabilities of senescent cells and treat diseases of aging caused by their accumulation,” Kuehnemann explained.
Working in the lab of HNRCA researcher Christopher Wiley, Kuehnemann focuses on a particular type of cell death called ferroptosis. Through ferroptosis, some endogenous omega-6 fatty acids cause the lipids in cell membranes to oxidize, which results in cells dying.
Crucially, this process kills off only senescent cells—not normal ones. Kuehnemann and fellow researchers are investigating ways to artificially induce ferroptosis in senescent cells in order to clear them and ultimately stop them from causing age-related illness.
In addition, Kuehnemann examines how some interventions—such as caloric restriction, which has been shown to reduce oxidative stress and damage—could help researchers characterize the importance of ferroptosis and, more generally, cell death, in health outcomes.
“The hope,” said Kuehnemann, “is that if we can learn enough about senescent cells to find the senolytics—agents that target senescent cells for removal—that can specifically target the problematic cells, this would help increase people’s healthspan.”