New therapy to target 'zombie cells' that spread inflammation

Israeli scientist in peer-reviewed study: Immunotherapy treatment could slow aging process

Israel Prize winner Prof. Michal Schwartz says her team’s work fighting Alzheimer’s can lead to treatments that boost immune system to slow down deterioration in brain – and body

Reporter at The Times of Israel

Israel Prize recipient Prof. Michal Schwartz blazes a trail toward anti-aging treatment through immune therapy (Courtesy of Weizmann Institute of Science)
Israel Prize recipient Prof. Michal Schwartz blazes a trail toward anti-aging treatment through immune therapy (Courtesy of Weizmann Institute of Science)

Pioneering scientist Michal Schwartz of the Weizmann Institute says that she and her team of researchers are close to developing a groundbreaking immunotherapy treatment that could help boost the immune system — and slow the aging process.

The research appeared in the peer-reviewed journal Neuron.

Schwartz, a 2023 Israel Prize recipient, was the first to discover that the brain is highly dependent on the immune system for its lifelong maintenance and function. She has spent the last 27 years studying the connection between the immune system and the aging brain.

Her international team of researchers now believes that an intervention to boost the immune system could potentially slow or even halt the aging of the brain as well as the body.

“We will soon be able to boost those immune cells that are most relevant to the brain,” Schwartz told The Times of Israel on a teleconference call.

“And the beauty is that I believe that whatever will boost the immune system to benefit the brain will benefit the entire body.”

Illustrative image: A human brain with degeneration, which is denoted in green. (Naeblys via iStock by Getty Images)

The immune system-brain connection

Schwartz published her first findings about the vital connection between the immune system and the brain in 1998.

Before then, the prevailing view was that the brain had evolved to function optimally without assistance from the immune system.

“People believed that if the immune system had access to the brain, it could affect it negatively,” Schwartz said.

The idea didn’t make sense to her, she said. It drove her to think that “something is wrong with the concept.”

But when Schwartz first wrote about her ideas, “everyone thought that I was crazy,” she said. “It took a lot of emotional resilience” for her to keep moving ahead with her revolutionary idea.

“After about eight years, the scientific community started to believe in my work and say, ‘Wow, she may be right,’” she said. For the past almost three decades she has continued to probe this field.

“When we age, the immune system becomes either insufficient or exhausted,” Schwartz said. “The aging immune system may not be the primary cause of brain aging, but it acts as a significant catalyst.”

She said that her data suggest that there is no need to treat the brain directly to prevent its aging or the development of neurodegenerative diseases.

Schwartz is the co-founder and chief scientific officer at ImmunoBrain, which is now conducting a clinical trial for an antibody to treat neurodegenerative diseases, including Alzheimer’s disease, the most common form of dementia.

The antibody is a protein component of the immune system that circulates in the blood, recognizes foreign substances like bacteria and viruses, and neutralizes them.

This approach “opens new avenues,” Schwartz said. The advancements in treatments for a brain disease like Alzheimer’s mean the possibility that “within the next two to three years, we will have a more sophisticated understanding of anti-aging immune-based treatments.”

Illustrative image: A doctor prescribing for an elderly patient (fizkes via IStock by Getty Images)

The senolytic cocktail

When the immune system ages, it undergoes a myriad of changes, Schwartz said.

There is increased inflammation or what is known as “inflamaging,” a term coined in 2000. This is categorized by chronic low-grade systemic inflammation that appears late in life, increasing the risk of age-related diseases such as cancer and neurodegenerative conditions.

Another result of an aging immune system is the accumulation of senescent cells, also known as “zombie cells,” which are no longer useful to the body.

According to the National Institute of Health website, even a small number of senescent cells can spread inflammation, “like the one moldy piece of fruit that corrupts the entire bowl.”

The selective elimination of senescent cells in the deteriorating immune system might mitigate the effects of aging, Schwartz said.

She believes that the right combination of drugs could provide a potential strategy for slowing down or delaying the effects of aging.

The class of drugs designed to specifically target these “zombie” cells is called senolytics.

Aged mice treated with a “senolytic cocktail” of a variety of drugs targeting these cells showed improved cognitive function, Schwartz said.

There is also research being done to identify a specific type of protein, called an epitope, that could boost an immune response in the brain.

A group of people practicing yoga. (JackF via iStock by Getty Images)

How to delay brain aging

While Schwartz said her research focuses on the immune system’s influence on brain aging, “it is essential to acknowledge that cognitive health is also shaped by genetics, hormonal balance, psychological well-being, and social factors.”

A lifestyle that includes regular physical exercise and balanced nutrition could reverse or delay the onset of typical symptoms of brain aging, she said.

Exercise has been shown to decrease inflammation, optimize brain function, and build resilience against aging.

A low-calorie diet can also markedly reduce inflammation. Limited calories were shown to enhance cerebral blood flow in the brains of young mice, contributing to the preservation of learning and long-term memory.

Healthful food sometimes contains a natural senolytic, Quercetin, which is found in green tea, coffee, various berries, apples, onions, broccoli, and citrus fruits.

Strawberries (Sarah Tuttle-Singer)

It is commonly understood that eating healthfully, exercising, getting enough sleep, and reducing stress can benefit brain health. According to Schwartz, all of these practices contribute to a better-functioning brain through — at least in part — their positive effects on the immune system.

When asked if she practices what she preaches, she admitted that she was “stressed and my nutrition is not optimal, but I’m doing a lot of exercise.”

Schwartz said her greatest source of stress relief “comes from my family and the joy of science.”

Meanwhile, she said, she is optimistic about her work.

“The ultimate goal is to prevent deterioration of the immune system,” Schwartz said. “And if this happens, we’ll be able to restore and boost it with the immune therapy treatment.”

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