senomorphics

Senomorphics are a class of compounds that modulate cellular senescence by altering the behavior or secretory profile of senescent cells rather than by eliminating them. The primary goal is to limit the detrimental effects of the senescence-associated secretory phenotype (SASP), a pro-inflammatory and tissue-disruptive set of factors secreted by many senescent cells, in order to reduce tissue dysfunction and age-related pathology.

Mechanisms often involve interfering with SASP signaling pathways such as NF-κB, JAK/STAT, and mTOR, or improving cellular stress responses. By dampening SASP factors like interleukins and proteases, senomorphics aim to preserve normal tissue structure and immune surveillance of damaged cells while delaying progression to full-blown senescence.

Examples and evidence are mainly from preclinical studies. Rapamycin and other mTOR inhibitors have been shown to suppress SASP in some senescent cells. JAK inhibitors, such as ruxolitinib, have reduced SASP cytokines in certain models. Metformin has been discussed as having senomorphic effects in some contexts, potentially via metabolic regulation. Research also explores NF-κB pathway inhibitors and other anti-inflammatory agents as senomorphics. It is important to note that most data come from cell culture and animal models; human data are limited and context-dependent.

Clinical potential and challenges include the possibility of reducing age-related tissue dysfunction without removing senescent cells, which could lower the risks associated with senolytics. However, challenges remain, including understanding the complexity of senescence biology, potential effects on immune surveillance, and the safety of chronic SASP modulation in humans.