Eliminating senescent cells to improve heart attack recovery

A drug that exterminates senescent cells improves recovery after a heart attack, according to new research, and could pave the way for a new heart attack treatment.

Researchers at Newcastle University found that after a heart attack dangerous senescent cells accumulate in the heart and prevent recovery. Senescent cells are sometimes called zombie cells – with very good reason.

Cells that reach the end of their useful lives and have stopped proliferating should expire, allowing their constituent proteins to be recycled by the body. However, senescent cells don’t die, but lurk in the body, secreting a cocktail of inflammatory chemicals, and encouraging otherwise healthy cells join them on the naughty step.

Longevity.Techology: Coronary heart disease (CHD) is the leading cause of heart attacks, and the biggest threat to Longevity, killing nearly 9 million people last year [1]. Improving post attack-recovery rates will improve both lifespan and healthspan, and understanding the role senescence cells play in heart health could play a part in improving heart Longevity and maybe even knock CHD off its top spot on the “Longevity Most Wanted” list.

The Newcastle team looked at the hearts of mice whose blood flow was restored after a heart attack and discovered various types of heart cells had become senescent. Inflammatory chemicals released by these senescent cells cause inflammation and scar tissue formation, meaning that the heart cannot pump normally.

During a heart attack the heart muscle becomes starved of blood and oxygen due to blockage of a coronary artery. Although treatment is often given to people to reopen the blocked artery and allow blood to flow back to the heart muscle the attack can still cause significant damage, even if if the heart muscle is rescued.

The researchers gave the mice navitoclax, a cancer treatment which is also known to trigger apoptosis, or cell death, in senescent cells. The mice received navitoclax daily for a week and when researchers inspected the mouse hearts 5 weeks later, they found that the reduction in senescent cells had the result of reducing inflammation, shrinking scar tissue and increasing the growth of blood vessels. In short, improved recovery of the heart muscle.

“Our work reveals that drugs to kill zombie cells could be transformational in the treatment of heart diseases.”

Using an MRI scanner, the team also investigated how well the mouse hearts were able to pump blood post heart-attack. Mice treated with navitoclax demonstrated significant improvements in their heart function and were able to pump blood around the body more effectively.

The Newcastle team, in collaboration with researchers at the Mayo Clinic in the US, Queen`s University Belfast and INSERM in France, now hope that this drug could be used within the next decade to help people recover from a heart attack and improve outcomes.
“We’ve discovered that removing these zombie cells can revitalise the heart after a heart attack,” Dr Gavin Richardson, lead author and Research Fellow at Newcastle University said. “Our work reveals that drugs to kill zombie cells could be transformational in the treatment of heart diseases.

“We now need to test the long-term impact of killing these cells and to ensure the drug is safe to be tested in humans. We hope that this zombie cell-killing drug could be treating heart attack patients in the next 5-10 years [2].”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “In the UK, heart attacks account for more than 100,000 hospital admissions – that’s one every five minutes. Thanks to decades of research advances, at least seven out of 10 people now survive a heart attack. But the increased number of people surviving a heart attack means that more people are living with damaged hearts.

“The heart can’t mend itself so effective treatments to help restore normal heart function after a heart attack are desperately needed. It’s early days yet, but if further research goes on to show that they are safe and effective in people, drugs that target senescent cells could provide an entirely new way of treating heart attacks [3].”

[1] https://www.who.int/news/item/09-12-2020-who-reveals-leading-causes-of-death-and-disability-worldwide-2000-2019
[2] https://inews.co.uk/news/science/heart-attack-survivors-hope-medical-breakthrough-759550
[3] https://www.bhf.org.uk/what-we-do/news-from-the-bhf/news-archive/2020/october/killing-zombie-cells-improves-heart-attack-recovery