New Research on ‘Zombie Cells’ Could Change Age-Related Treatments

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The team’s breakthrough centers around a protein called PD-L1, which is known for its role in helping cancer cells evade immune detection.

By Pesach Benson, TPS

Israeli scientists uncovered how aging cells evade the immune system, offering new hope for the treatment of age-related conditions such as cardiovascular disease, diabetes and neurodegenerative disorders.

While the study, conducted by the Weizmann Institute in Rehovot, does not represent a “fountain of youth, the findings move science closer to slowing down the biological processes of aging to extend healthy life.

The findings, published in the peer-reviewed Natural Cell Biology journal, propose using immunotherapy to target “senescent cells,” which are often referred to as “zombie cells.”

Unlike normal cells that either divide or die, senescent cells stop dividing but remain metabolically active. As these cells persist, they accumulate in body tissue, contributing to chronic inflammation and other age-related diseases.

Scientists have long sought to eliminate senescent cells, but no drugs exist that can efficiently target them.

The researchers, led by Dr. Julia Majewska and Dr. Amit Agrawal, found that senescent cells exploit the immune system, blocking its ability to clear them out, similar to how cancer cells evade immune responses.

The team’s breakthrough centers around a protein called PD-L1, which is known for its role in helping cancer cells evade immune detection. Senescent cells, they found, also produce high levels of PD-L1, effectively cloaking themselves from the immune system.

The researchers discovered a direct link between PD-L1 and another protein, p16, which plays a role in halting cell division as part of the aging process.

As levels of p16 rise, so too do levels of PD-L1, suppressing the immune system’s ability to recognize and destroy senescent cells.

“This discovery is critical,” said Prof. Valery Krizhanovsky, in whose laboratory the study took place. “It shows how senescent cells manage to persist in aging tissues and chronic conditions, opening the door for targeted interventions.”

To test their theory, the team turned to an antibody already approved for cancer treatment, designed to target PD-L1.

Administering this antibody in aging mice, as well as mice with lung inflammation, they observed a significant reduction in senescent cells.

The antibody effectively reactivated T cells and other immune cells, enabling them to clear out the aging cells.

“While the treatment didn’t halt aging, it successfully reduced inflammation-related proteins and senescent cell numbers in mice,” Krizhanovsky explained.

The implications extend beyond aging. The study also linked high levels of PD-L1 and p16 in senescent cells to chronic obstructive pulmonary disease (COPD), a condition commonly found in smokers.

Patients with COPD were found to have elevated levels of these proteins, suggesting that the therapy could potentially be applied to various chronic disorders.

The researchers are now focusing on refining the treatment by engineering antibodies that can target both PD-L1 and specific aging markers.

This dual-target approach could ensure higher precision in eliminating senescent cells while minimizing potential side effects.

“We believe this discovery could transform the use of immunotherapy,” Krizhanovsky said. “Beyond cancer, it offers a promising pathway for treating age-related diseases and chronic inflammation, conditions that affect millions worldwide.”

Senescent cells comprise less than 1% of cells in young bodies but can account for up to 15% in aged tissues.

Therapy targeting senescent cells could potentially delay the onset of age-related diseases such as osteoporosis, cardiovascular diseases, and neurodegenerative disorders such as Alzheimer’s. Senesent cells are also known to

Such treatment could also potentially alleviate symptoms and slow the progressesion of other conditions such as such as rheumatoid arthritis.inflammatory bowel disease, psoriasis, and certain diseases of the liver.