Reversing Cellular Senescence: A New Frontier in Treating Age-Related Disease

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• Senescence and the Aging Process
• The Direct Link to Age-Related Disease
• The Inflammatory Impact of Senescent Cells
• Senolytic Therapy: Clearing Damaged Cells
• Future Research and Human Trials
• Full Transcript

Senescence and the Aging Process

Cellular senescence is a fundamental hallmark of biological aging. Dr. Andrea Maier, MD, describes it as a state where cells lose their capacity to divide. These non-dividing senescent cells do not leave the body. Instead, they begin to accumulate from around the age of 30 onwards. Dr. Anton Titov, MD, explores this concept in the interview. The number of these dysfunctional cells increases significantly with chronological age. A body at age 80 will harbor a much higher number of senescent cells than a body at age 30 or 40.

The Direct Link to Age-Related Disease

The accumulation of senescent cells is not a harmless process. Dr. Andrea Maier, MD, explains that these cells are directly detrimental to health. Research shows a strong correlation between high senescent cell burden and the presence of specific age-related diseases. Studies compare individuals of the same chronological age. Those with conditions like Chronic Obstructive Pulmonary Disease (COPD), cardiovascular disease, or renal dysfunction have far more senescent cells in affected organs. This evidence suggests senescent cells are not just a marker of aging but a potential cause of disease.

The Inflammatory Impact of Senescent Cells

Senescent cells damage tissues through a process known as the senescence-associated secretory phenotype (SASP). As Dr. Andrea Maier, MD, details, these cells secrete a flood of inflammatory cytokines. This is a distress signal to neighboring cells. The resulting local inflammation and stimulation of unwanted cell replication create a toxic microenvironment. This chronic, low-grade inflammation is a known driver of pathologies like atherosclerosis. The forced replication of nearby cells also increases the risk of cancerous growths.

Senolytic Therapy: Clearing Damaged Cells

The logical next step is to find ways to remove these harmful cells. Dr. Andrea Maier, MD, discusses an exciting new class of drugs called senolytics. These compounds are designed to target senescent cells specifically. They work by pushing these cells into a programmed cell death process called apoptosis. Once the senescent cell undergoes apoptosis, the body's immune system clears the debris. This leaves the tissue environment cleaner and free from the damaging signals that promote disease progression.

Future Research and Human Trials

The potential of senolytic therapy is immense. Dr. Andrea Maier, MD, notes that studies in mice have been promising. Treatment with senolytics has been shown to increase both healthspan (the period of life free from disease) and overall lifespan. The conversation with Dr. Anton Titov, MD, highlights that this research is now moving into human trials. Scientists are actively testing whether administering senolytics to people can lower biological age and delay the onset of age-related illnesses. This represents a paradigm shift from managing age-related disease to potentially preventing it.

Full Transcript

Dr. Anton Titov, MD: How does cellular senescence relate to human disease and aging, if we talk about cellular senescence? And is it possible to reverse cellular senescence?

Dr. Andrea Maier, MD: Yes, cellular senescence is one of the hallmarks of aging. Cellular senescence is a state of cells where the cells are not dividing anymore. They are still in the body, but they lost the capacity to divide normally.

Our cells have the capacity to divide and replicate. There are lots of studies, especially in aging individuals from the age of 30 onwards, showing that these senescent cells are accumulating with chronological age. It means that at the age of 60, 70, or 80, there is a higher number of senescent cells compared to a body which is 30 years of age or 40 years of age.

The accumulation of the number of senescent cells in a body is higher at higher chronological age. Then you might ask yourself, okay, so what is that? Is that detrimental? Yes, it is.

We think that once a cell is in a senescent stage, that senescent cell is influencing the environment negatively. The cell lost the function of replication, of doubling itself, and is asking other cells in the environment for help. It secretes lots of inflammatory cytokines, for example, to say, "Hey, I'm senescent. You might want to know this, and I need your help. What should I do?"

So the senescent cells influence the microenvironment. Other tissues in the surrounding area are negatively affected. Inflammation and cellular replication is induced. So doubling happens of neighboring cells, which should not replicate.

There is always the risk for atherosclerosis, which is associated with inflammation, or cancer, which is, of course, associated with replication of cells at a higher rate. And that's what we were able to show.

Not only do people with higher age have a higher number of senescent cells, but especially the people with age-related diseases. For example, COPD, which is a lung disease, or cardiovascular disease, or renal dysfunction. In kidney disease, these organs had many more senescent cells than age-matched controls.

It means individuals have the same chronological age but do not have that disease. So we know that senescent cells might be bad. They might be the cause of age-related diseases.

And then, of course, the question is, can we remove senescent cells? That's an entirely new field of research using senolytics. The senescent cells are being driven into a state called apoptosis. So they kill themselves with the idea that if that cell kills itself and it is eaten up by the immune system, now there is a clear tissue.

Senescent cells are not there to induce the disease. So it's a clearance of senescent cells. And there are some human trials also ongoing to see and test if the biological age would be lower if you apply senolytics to human beings.

My studies have proven that it works to increase the healthspan and the lifespan. So the years without diseases, or the months without diseases in mice, increase. It increases the chance of longevity.