Elimination of Senescent Cells by Polyphenols and Flavonoids

Abstract

Oxidative stress, oncogenic signaling, DNA damage, or shortened telomeres, among other stimuli, can lead to cellular senescence. Senescent cells develop a secretory phenotype (SASP) that secretes factors such as inflammatory cytokines, growth factors, or metalloproteases into the surrounding tissue. These factors can create an environment that favors tumor growth. Senescent cells are more resistant to apoptosis than young cells, and this state may be a refuge for cancer cells to survive chemotherapies by switching between states. Polyphenols can mitigate SASP, but also act directly against senescent cells. Substances that selectively kill senescent cells are called senolytics. Quercetin and fisetin are substances that are thought to have these properties, and these substances are already being studied in clinical trials. Polyphenols may interfere with cellular senescence and its consequences through different mechanisms and alleviate age-associated diseases such as cancer.