Role of the trophoblast secretome in senescence and aging

National Institute On Aging

Investigators

Abstract

The senescence-associated secretory phenotype (SASP) is a hallmark of cellular senescence and a key driver of age-related inflammation and tissue dysfunction. Targeting SASP through senotherapeutic approaches holds promise for mitigating aging-associated diseases. We found that extracellular vesicles (EVs) and secreted factors from human trophoblast stem cells (hTSCs) have the potential to modulate cellular aging. Here, we propose to investigate the ability of hTSC-derived secretome (hTSC-S) and hTSC EVs to suppress SASP and restore cellular homeostasis. We will isolate and characterize hTSC EVs using size exclusion chromatography and employ RNA sequencing to identify key molecular cargo mediating their anti-senescence effects and we will assess the impact of hTSC-S and hTSC EVs on senescence-associated traits in WI-38 fibroblasts by evaluating inflammatory signaling, mitochondrial function, oxidative stress, and epigenetic modifications. Ultimately, we will determine their therapeutic potential in aged mice by analyzing inflammatory markers and aging-related phenotypes following hTSC-S or EV treatment.