Miller William C, Yousefzadeh Matthew J, Fisher Jessica, Sarumi Heidi, Kirchner Varvara, Niedernhofer Laura J, Pruett Timothy
University of Minnesota Medical School, Minneapolis, MN, USA.
Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA.
Geroscience. 2024 Dec 30. doi: 10.1007/s11357-024-01482-9.
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 and p21 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 and p21 (r = 0.5092, p-value = 0.0205; r = 0.5339, p-value = 0.0164, respectively). A similar correlation occurred between p16 and p21 expression and length of hospitalization (r = 0.4960, p-value = 0.0230; r = 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.
需要肝脏移植的老年个体比例正在增加，导致患者群体日益衰弱。衰弱是与衰老相关的一系列认知和身体症状，会增加发病和死亡风险。细胞衰老 是一种对压力作出反应的程序性细胞命运，与衰弱、年龄相关疾病以及衰老本身有关。本研究探讨细胞衰老、身体衰弱与肝脏移植之间的关系。纳入了2022年9月1日至2022年11月30日期间在我们中心接受门诊肝脏移植的18岁以上成年人。使用肝脏衰弱指数™进行衰弱评估，并在移植前采集血液。通过RT-qPCR测量T细胞中p16和p21 mRNA的表达，这是一种用于衡量衰老细胞负担的既定指标，并通过多重ELISA测量衰老相关分泌表型蛋白的血浆水平。通过电子病历收集患者的预后情况。单变量线性回归分析表明，患者基线衰弱与p16和p21之间存在统计学上的显著关系（r分别为0.5092，p值为0.0205；r为0.5339，p值为0.0164）。p16和p21表达与住院时间之间也存在类似的相关性（r分别为0.4960，p值为0.0230；r为0.5868，p值为0.0098）。本研究揭示了细胞衰老生物标志物、身体衰弱与住院时间之间的潜在关联。鉴于需要将患者分层的生物标志物，并且存在减少衰老细胞负担的治疗方法，可用于改善移植结果，因此有必要对此进行进一步研究。
