Talk like a molecular biologist

Cellular senescence — a state in which damaged or stressed cells permanently stop dividing but remain metabolically active, often releasing molecules that cause inflammation, fibrosis and tissue dysfunction

Fibrosis — the excessive build-up of structural proteins, leading to tissue stiffening and impaired organ function

Inflammation — the body’s response to injury or stress that can cause swelling, redness and tissue damage

Mitochondria — tiny structures inside cells that generate energy, regulate cell death and play a central role in the onset of cellular senescence

Metabolic diseases — disorders that affect how the body processes and uses energy from food, often leading to conditions like obesity and diabetes

Senolytic compounds — drugs designed to selectively remove senescent cells from the body

In 1800, the average person lived for around 40 years; today, that number is closer to 80. However, living longer does not always mean living well. There is a growing gap between lifespan – the total number of years we live – and healthspan – the number of those years spent in good health.

“Around the world, people are living longer but often spend those extra years managing chronic illnesses like diabetes, cardiovascular disease and cancer,” says Dr Soňa Štemberková Hubáčková from the Laboratory of Translational and Experimental Diabetology and Obesitology (LTEDO) at the Institute for Clinical and Experimental Medicine. “Most current therapies primarily alleviate symptoms or slow disease progression but do not address the underlying biological mechanisms driving the illness.”

What is cellular senescence?

Research at the LTEDO focuses on cellular senescence, a fundamental biological process that links ageing, inflammation and the gradual decline of tissues. Normally, when cells become damaged or stressed, they stop dividing and destroy themselves to prevent further harm. But during senescence, instead of quietly disappearing, some of these cells linger – alive but no longer useful.

“Senescent cells are like ‘zombie cells’ that have stopped dividing but refuse to die, releasing a wide range of inflammatory and tissue-remodelling molecules,” explains Soňa. Over time, these cells build up throughout the body, creating a constant, low level of inflammation that contributes to age-related decline.

While cellular senescence begins as a protective mechanism, its long-term effects are damaging. The process is linked to many chronic conditions, including obesity, type 2 diabetes, cardiovascular disease, liver and kidney disorders, and neurodegenerative diseases. Senescence can even play a double role in cancer – helping to suppress tumour growth at first, but later encouraging it through inflammation and fibrosis.

How can we destroy senescent cells?

If senescent cells drive ageing and disease, then how can we remove them? The LTEDO team has developed a series of senolytic compounds – drugs designed to seek out and destroy senescent cells while leaving healthy ones intact.

This work began with a compound called MitoTam, originally created as an anti-cancer drug in Professor Jiří Neužil’s laboratory at the Institute of Biotechnology of the Czech Academy of Sciences. When Soňa tested MitoTam, she discovered that it also had a strong senolytic effect. “Building on these findings, the team at the LTEDO developed and patented a new generation of mitochondria-targeting senolytic agents that eliminate senescent cells by exploiting their characteristic metabolic and structural vulnerabilities,” explains Soňa.

These compounds specifically target mitochondria, the energy centres inside cells that are involved in maintaining senescence. Once inside the mitochondria, these senolytic compounds disrupt their structure and energy supply, triggering the controlled death of senescent cells. Healthy cells, which are more adaptable, remain largely unaffected.

How does the team test the senolytic compounds?

To study their senolytic compounds, the LTEDO team combines in vitro and in vivo experiments – meaning they test them both in the lab and in living organisms. In their in vitro studies, they induce senescence in cultured human and animal cells, allowing them to closely examine how the senolytic compounds affect mitochondrial function, cell survival and the secretion of inflammatory molecules. These experiments reveal the cellular mechanisms behind each compound’s action and help optimise their selectivity and dosing.