Can aging be treated at the cellular level?

For some, January is a time for resolutions, with the goal often tied to being fitter and healthier. And increasingly this has included a fixation on addressing aging at the cellular level, driven in part by the rise of “biohacking.”

“People don't want to die—that’s been true forever,” says Penn Integrates Knowledge University Professor Shelley Berger. “But now, some people think that with enough money, new ideas, and brainpower, aging is a disease that can be ‘solved.’”

“Aging isn’t a switch you can turn off,” adds Sinem Esra Sahingur, an associate professor in the Penn Dental Medicine’s Department of Periodontics. “But understanding processes like senescence opens the door to healthier aging.”

Penn Today spoke with Berger, who has appointments in the Perelman School of Medicine and the School of Arts & Sciences; Zhihui Zhang, a postdoctoral researcher in her lab; and Sahingur to better understand senescence, the process of cellular aging, now front and center as a potential anti-aging target.

Senescence is a normal process

Originally considered merely a cellular phenomenon and not relevant to organisms, senescence is actually a protective strategy that cells use when faced with stress or damage, explains Berger. “Loss of control over cell growth is happening all the time in our bodies. Senescence is one way to stop damaged cells from dividing.”

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Zhang notes, “Senescence is also needed for tissue regeneration and development,” citing the important role senescence plays in wound healing as an example. When tissues are injured, he explains, senescent cells release signals such as cytokines and growth factors that activate the immune system, promote repair, and help limit scarring before they are cleared by immune cells.

Aging is fueled by the accumulation of senescent cells

When senescence becomes problematic, says Sahingur, is when senescent cells are not cleared in a timely fashion. “We don’t want too many, and we want them to be eliminated because they become a burden to tissues,” she says, noting that these cells are sometimes called ‘zombie cells’ because they are damaged but continue to live, recruiting neighboring cells into senescence. It is the accumulation of senescent cells that accelerates aging.

“As we age, senescent cells accumulate,” Sahingur continues. “And with that you get tissue dysfunction, metabolic alterations, and so on.” This arises in part because aging immune systems become less efficient at clearing senescent cells—a process called immunosenescence—allowing these cells to persist and drive chronic inflammation, she adds.

When you are young, adds Zhang, it is good to have stronger immunity, as you are often facing unknown pathogens. But as you age, you don’t need that much inflammation. And as you age, more environmental stressors leading to more tissue damage and more senescent cells will cause the overactivation of the immune system.

One study sparked the current interest in senescence

Berger traces the growing public interest in targeting senescent cells as an approach to slow aging and improve health span—the years spent living in good health—to a specific, non-Penn study done a few years ago.

In this study, Berger says, researchers eliminated all senescent cells from the outset in a mouse model and found that “the mice were better in many ways. They lived longer. They were healthier.”

These findings, she says, led to the idea that drugs capable of eliminating senescent cells as they arise could—to the extent that senescence is a driver of aging—“lead to a treatment for aging as a disease—a disease of too many, out-of-control senescent cells.”

Translating senescent cell research into therapies is complex

But, Berger notes, mice are not humans.

Zhang explains that cellular differences—such as the ability of mice to replenish lost cells efficiently—allow them to benefit from this form of aggressive cell removal in ways that humans cannot.

He notes that this study also highlights the challenges of translating this approach to humans, even as additional preclinical studies have reported the therapeutic benefits of targeting senescent cells.

For example, a 2025 preclinical study by Sahingur and colleagues in the Journal of Dental Research showed that the senolytic combination of dasatinib and quercetin reduced senescent cell burden, inflammatory signaling, and bone loss in aging periodontal tissues—without eliminating senescence entirely.

“We don’t want to shut down the senescence response completely,” says Sahingur. “Senescence is context dependent. It can be harmful, but it can also be necessary.”

One major challenge is specificity. “Unfortunately, even today, there is not one single marker of senescence,” Sahingur says. “You can’t just look at one single marker and say that this cell is senescent. And we don’t want to target non-senescent cells.”

Better biomarkers could help, says Berger, particularly ones that distinguish different types of senescence in different tissues. “But we’re a long way from that,” she adds.

Next steps

“We need better ways of understanding senescence in healthy humans,” says Berger. “Aging is complex—it is going to be different in different tissues and cell types, so we need to understand it much better.”

Sahingur concurs, emphasizing that her team’s focus is not on chasing immortality but on preserving tissue function and resilience across the lifespan.

“The goal is not to stop aging,” she says. “It’s to understand how aging-related processes like senescence contribute to disease—and how we can intervene safely and intelligently.”

Shelley Berger is a Penn Integrates Knowledge University Professor with appointments in both the Perelman School of Medicine and School of Arts & Sciences at the University of Pennsylvania. She is the Daniel S. Och University Professor and a professor in the Department of Cell and Developmental Biology at Penn Medicine and a professor in the Department of Biology in Penn Arts & Sciences. Berger is also the founding director of the Penn Epigenetics Program. 

Sinem Esra Sahingur is an associate professor in the Department of Periodontics and the associate dean of graduate studies and student research at Penn Dental Medicine.

Zhihui Zhang is a postdoctoral researcher in the Berger Lab.