Lee Da-Yeon, Lee Su-Jeong, Chandrasekaran Prabha, Lamichhane Gopal, O'Connell Jennifer F, Egan Josephine M, Kim Yoo
Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD 21224, USA.
Antioxidants (Basel). 2023 May 27;12(6):1165. doi: 10.3390/antiox12061165.
Dietary interventions with bioactive compounds have been found to suppress the accumulation of senescent cells and senescence-associated secretory phenotypes (SASPs). One such compound, curcumin (CUR), has beneficial health and biological effects, including antioxidant and anti-inflammatory properties, but its ability to prevent hepatic cellular senescence is unclear. The objective of this study was to investigate the effects of dietary CUR as an antioxidant on hepatic cellular senescence and determine its benefits on aged mice. We screened the hepatic transcriptome and found that CUR supplementation led to the downregulation of senescence-associated hepatic gene expressions in both usually fed and nutritionally challenged aged mice. Our results showed that CUR supplementation enhanced antioxidant properties and suppressed mitogen-activated protein kinase (MAPK) signaling cascades in the liver, particularly c-Jun N-terminal kinase (JNK) in aged mice and p38 in diet-induced obese aged mice. Furthermore, dietary CUR decreased the phosphorylation of nuclear factor-κB (NF-κB), a downstream transcription factor of JNK and p38, and inhibited the mRNA expression of proinflammatory cytokines and SASPs. The potency of CUR administration was demonstrated in aged mice via enhanced insulin homeostasis along with declined body weight. Taken together, these results suggest that CUR supplementation may be a nutritional strategy to prevent hepatic cellular senescence.
已发现含有生物活性化合物的饮食干预可抑制衰老细胞的积累和衰老相关分泌表型（SASP）。姜黄素（CUR）就是这样一种化合物，它具有有益的健康和生物学作用，包括抗氧化和抗炎特性，但其预防肝细胞衰老的能力尚不清楚。本研究的目的是调查作为抗氧化剂的饮食姜黄素对肝细胞衰老的影响，并确定其对衰老小鼠的益处。我们筛选了肝脏转录组，发现补充姜黄素可导致正常喂养和营养应激衰老小鼠中衰老相关肝脏基因表达的下调。我们的结果表明，补充姜黄素可增强抗氧化特性，并抑制肝脏中的丝裂原活化蛋白激酶（MAPK）信号级联反应，特别是衰老小鼠中的c-Jun氨基末端激酶（JNK）和饮食诱导肥胖衰老小鼠中的p38。此外，饮食姜黄素可降低核因子-κB（NF-κB）的磷酸化，NF-κB是JNK和p38的下游转录因子，并抑制促炎细胞因子和SASP的mRNA表达。通过增强胰岛素稳态以及降低体重，在衰老小鼠中证明了姜黄素给药的效力。综上所述，这些结果表明补充姜黄素可能是预防肝细胞衰老的一种营养策略。
