Longevity Briefs: Apigenin, A Natural Way To Combat ‘Zombie Cells’?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Each time a cell divides, its telomeres – the protective caps on the ends of each chromosome – get a little shorter. Once too much telomere shortening has occurred, the cell is no longer able to divide without losing essential genetic information and stops dividing permanently, entering a state called senescence. Senescent cells are thought to play an important role in the ageing process. They accumulate with age and release harmful substances (the senescence-associated secretory phenotype or SASP), contributing to inflammation and tissue damage and promoting many age-related diseases including cancer.

What can be done about these troublesome cells? Some drugs (senolytics) are capable of removing senescent cells, while others (senomorphics) focus on reducing the harmful effects of the SASP. The search for safe and effective drugs that can limit the burden of senescent cells is a promising but challenging area of research. In this study, researchers use a screening approach to search for natural compounds that might target senescent cells.

The discovery:

Researchers screened a library of 66 natural products to identify compounds that could target senescent cells. To do this, they took human prostate cells (PSC27) and exposed them to bleomycin, a chemotherapy drug that can cause cells to become senescent. They tested the 66 natural compounds to see if they could either kill senescent cells or suppress the harmful factors they released. While no new senolytics were identified, the researchers did identify several compounds that suppressed the release of SASP factors. One standout was apigenin, a type of natural plant compound called a flavonoid. Flavonoids are of scientific interest due to their antioxidant and anti-inflammatory properties. The researchers decided to focus the rest of the study on this compound.

Researchers first tested the possibility that apigenin might suppress tumour growth, since the SASP plays a role in supporting nearby cancer cells. They cultured senescent cells together with prostate cancer cells, and found that the addition of apigenin significantly reduced tumour growth.

Next, they moved to tests in live animals. Using mice with premature ageing induced by radiation, they demonstrated that apigenin improved physical function (grip strength, endurance, balance), and cognitive function (memory, anxiety) compared to a control treatment. They also showed that mice that had received human prostate cancer grafts responded significantly better to chemotherapy when they were also treated with apigenin.

The implications:

This research suggests that apigenin, a naturally occurring compound, could be a valuable tool in combating age-related deterioration and could potentially enhance the effectiveness of cancer treatments. Relatively recently, scientists have realised that tumour cells themselves are not the only enemies when it comes to cancer treatment. Tumours tend to promote senescence in nearby cells, and the SASP factors that these cells release create an environment that helps the cancer to survive and grow. To make matters worse, the ‘collateral damage’ caused by chemotherapy turns even more cells senescent, hindering treatment and making cancers more likely to return even after they have been destroyed.

While flavonoids like apigenin look promising on paper, they are not very well absorbed by the human body and also get broken down quite quickly. Studies investigating the effects of these compounds show mixed results and are generally of poor quality. Still, foods that are apigenin-rich such as parsley, celery and chamomile tea are considered healthy for other reasons, so incorporating more of them into your diet is unlikely to be a bad idea.