Senescent cells disrupt heart repair after a heart attack

When a blocked artery cuts off oxygen to part of the heart, surviving cells can enter a state called cellular senescence. They stop dividing and begin secreting a mixture of inflammatory molecules, collectively known as the senescence-associated secretory phenotype (SASP). In the short term, this is helpful: SASP factors recruit immune cells that clear dead tissue and coordinate scar formation.

However, the researchers describe how this process becomes harmful when senescent cells persist too long. In the scar zone, prolonged SASP over-stabilises tissue. In the adjacent border zone, it disrupts electrical conduction, potentially triggering arrhythmias. In the surrounding healthy tissue, it drives compensatory remodelling that can eventually lead to heart failure.

Timing and location determine the outcome

A key insight from this review is that the SASP is not uniform across space or time. In the acute phase, immediately after the arterial blockage, SASP amplifies inflammation and immune recruitment. In the subacute phase, it helps resolve inflammation and form scar tissue. In the chronic phase, weeks to months later, it promotes pathological fibrosis and electrical instability. Simply eliminating all senescent cells right after a heart attack would likely be counterproductive, disrupting the early healing response the body needs.

Senolytic therapy as a timing problem

The researchers suggest that senolytic treatments, which selectively destroy senescent cells, could benefit cardiac patients if applied at the right moment. The optimal timing has not yet been established. Earlier work already demonstrated that senolytics such as dasatinib and quercetin can effectively remove senescent cells from aging tissues. Whether a time-targeted application after myocardial infarction can limit chronic cardiac damage remains to be tested in clinical trials that have not yet been carried out.

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