A brief report on biomarkers of cellular senescence associated with liver frailty and length of stay in liver transplantation

The proportion of older individuals needing liver transplantation is growing, resulting in an increasingly frail patient population. Frailty constitutes a constellation of cognitive and physical symptoms associated with aging and increases the risk of morbidity and mortality. Senescence is a programmed cell fate in response to stress implicated in causing frailty, age-related diseases, and aging itself. This study explores the relationship between cellular senescence, physical frailty, and liver transplantation. Adults > 18 years old who underwent ambulatory liver transplantation at our center between September 1, 2022, and November 30, 2022, were included. Frailty assessments were performed using the Liver Frailty Index™, and blood was collected prior to transplantation. Expression of p16^INK4a and p21^CIP1 mRNA in T cells was measured by RT-qPCR, an established proxy for senescent cell burden, and plasma levels of senescence-associated secretory phenotype proteins were measured by multiplex ELISA. Patient outcomes were collected via electronic medical record. Univariate linear regression analysis demonstrated a statistically significant relationship between baseline patient frailty and p16^INK4a and p21^CIP1 (r² = 0.5092, p-value = 0.0205; r² = 0.5339, p-value = 0.0164, respectively). A similar correlation occurred between p16^INK4a and p21^CIP1 expression and length of hospitalization (r² = 0.4960, p-value = 0.0230; r² = 0.5868, p-value = 0.0098, respectively). This study revealed a potential association between biomarkers of cellular senescence, physical frailty, and length of hospitalization. This warrants further investigation as biomarkers to stratify patients are needed and therapeutics to reduce senescent cell burden exists and could be deployed to improve transplant outcomes.