Nobiletin Delays Aging and Enhances Stress Resistance of Caenorhabditis elegans

Abstract

Nobiletin (NOB), one of polymethoxyflavone existing in citrus fruits, has been reported to exhibit a multitude of biological properties, including anti-inflammation, anti-oxidation, anti-atherosclerosis, neuroprotection, and anti-tumor activity. However, little is known about the anti-aging effect of NOB. The objective of this study was to determine the effects of NOB on lifespan, stress resistance, and its associated gene expression. Using Caenorhabditis elegans, an in vivo nematode model, we found that NOB remarkably extended the lifespan; slowed aging-related functional declines; and increased the resistance against various stressors, including heat shock and ultraviolet radiation. Also, NOB reduced the effects of paraquat stressor on nematodes and scavenged reactive oxygen species (ROS). Furthermore, gene expression revealed that NOB upregulated the expression of sod-3, hsp-16.2, gst-4, skn-1, sek-1, and sir-2.1, which was suggested that anti-aging activity of NOB was mediated most likely by activation of the target genes of the transcription factors including dauer formation (DAF)-16, heat-shock transcription factor (HSF)-1, and skinhead (SKN)-1. In summary, NOB has potential application in extension of lifespan, and its associated healthspan and stress resistances.

Nobiletin Protects Against Diabetes-induced Testicular Injury via Hypophysis-gonadal Axis Up-regulation and Amelioration of Oxidative Stress

“…Many studies have revealed that nobiletin could improve the antioxidant defense and decreases lipid peroxidation [75,76,17]. This antioxidant effect may be gifted by modifying the antioxidants gene manifestation [77], free radical reducing action [17], or by decreasing hyperglycemia [78]. The antioxidant effect of nobiletin is in agreement with the results of Bi et al [75].…”

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

“…The NOB is suggested to be beneficial in this case. An experiment on Caenorhabditis elegans exhibits that NOB has great antitumor activity and can enhance the lifespan by attenuation of heat shock and ultraviolet radiation [74]. We earlier mentioned that NOB is advantageous in suppressing iron overload-mediated oxidative stress.…”

Autophagy Plays a Role in the Prolongation of the Life Span of Caenorhabditis elegans by Astaxanthin

“…IIS pathway is an evolutionarily conserved central regulatory pathway similar to human aging process. It plays an important role in the regulation of longevity of nematodes and mammals by regulating the conserved transcription factor DAF-16, 14,43 and the activation of daf-16 leads to increased longevity, stress resistance, and the induction of heat-shock genes such as old-1, sod-3, and small heatshock-related protein chaperones. [44][45][46][47] Koumei Yazaki et al and Xiaojuan Liu et al found that AST could keep the optimal intracellular ROS balance by modulating genes involved in IIS pathway and the oxidoreductase system.…”