Development of a novel metabolic glyco-sensing approach with anti-aging potential

Abstract

Senescent cells, characterized by irreversible cell cycle arrest, are known to accumulate during aging and their accumulation in aged tissues, in turn, accelerates aging process and promotes age-related diseases. Therefore, targeting senescent cells is an attractive strategy for anti-aging or to delay features of aging. Here, we develop a glyco-sensing approach to specifically eliminate senescent cells using rat luminal ductal epithelial (LDE) breast milk cells as a model system. Senescent LDE cells, when treated with a metabolic sugar sialic acid (SA) under nutrient deprived condition, undergo ~3-fold (p<0.001) more apoptosis compared to LDE adult cells as demonstrated by TUNEL assay. On SA binding lectin assays, particularly with Maackia amurensis lectin I (MAL-I), senescent cells show more sialylation compared to the adult cells, possibly causing more apoptosis on these cells. This study is the first to show that SA supplementation can be protective to aging cells experiencing nutrient scarcity, while specifically killing senescent cells implying a possible role in anti-aging. Moreover, SA supplementation under nutrient deprived condition could be a strategic marker to distinguish senescent cells from adult or aging cells.