Discovery of longevity genes such as SirT

Discovery of longevity genes such as SirT gene family has resulted in tremendous enthusiasm among many scientists. Numerous studies have shown that this gene family uses intermediate metabolites such as acetyl-CoA, ATP, and NAD+ or nucleosomes to modify and control the activity and expression of cdc42 inhibitor involved in the central metabolic pathways. SirT gene can prolong lifespan by reducing catabolism. In contrast, the body can strengthen catabolism and cell proliferation during overnutrition so that it is inevitable to cause various diseases and even to shorten lifespan. As emphasized by Ryan and Seeley [117], foods and nutrition are the basis for biological subsistence. Moreover, due to hormone-like activity, they transfer various signals to the body to control the metabolism and physiological activities through complicated interactions with the GI system and cell receptors in vivo. Meanwhile, many compounds from fruits and vegetables, although not considered as nutrients, regulate life activities such as appetite and basic metabolic status by interacting with receptors. Studies on these issues may provide us personalized nutrition and food recipes. Future research should focus on GPCRs, mTOR, TLRs, and nuclear receptors and their interactions with diet compositions. Studies on signal functions of all nutrients should also be performed. After years of efforts, we have established a set of methods suitable for the functional evaluation of foods and drugs in vivo, i.e., intercellular wireless communication network. Because it is a directed weighted network, it enables us to quantitatively depict its characteristics by using various parameters from various angles by referring to biological macromolecular interaction network models, i.e., the undirected unweighted network and directed weighted metabolic network. Foods are closely correlated with nutritional metabolism. We have successfully created flux and flux control analysis suitable for the study based on the central metabolic pathway in human body. This established method can quantitatively evaluate the effects of foods on metabolic network because it quantitatively explores the roles of foods in synthesis and catabolism in vivo. In addition, because the analysis involves obtaining peripheral blood, it serves as a noninvasive method to provide a novel strategy for the quantitative evaluation of functional foods in vivo.
Background Medicinal use of citrus peels, such as aged tangerine peels in south east Asia, can be traced back to 10th century BC. However, the systematic in-depth exploration of the biological activity of citrus peels did not embark until the last decade, when advanced flavonoid profiles in citrus peels were established and isolation of majority of individual flavonoids became available. Since then, a plethora of biological properties important to health and diseases have been identified [1–3]. In addition to cancer prevention and intervention, other biological functions of compounds from citrus peels investigated include inflammation inhibition [4–7], hypolipidemia [8,9], regulation of metabolic syndrome [10–13], delayed onset of Alzheimer\'s disease [14,15] and more. Characterization of the phytochemical composition of citrus peels with modern analytical technology indicated that citrus peels are an abundant source of polyhydroxyl flavonoids (PHFs) such as hesperidin, neohesperidin and naringin; and almost the sole source of polymethoxyflavones (PMFs) with high content, which are mainly represented by nobiletin, tangeretin, sinesetin, 3,5,6,7,8,3′,4′-heptamethoxyflavone and 3,5,6,7,3′,4′-hexamethoxyflavone [3,16,17]. Research in anti-cancer activity of citrus flavonoids has been majorly focused on in vitro experiments to elucidate action mechanisms such as anti-proliferative effects, enzyme inhibition and cancer cell attenuation. PMFs have demonstrated the growth inhibition of human leukemic cell (HL-60) lines [18]. Of PMFs, tangeretin played important inhibitory roles in cancer-cell proliferation and metastasis stage by inhibiting cell adhesion and invasion [19]; showed cell cycle arrest in G1 phase by inhibiting cyclin-dependent kinases (Cdk) and enhancing Cdk inhibitor proteins [20]; inhibited extra cellular-signaling-regulated kinase 1/2 (ERK1/2) phosphorylation and growth of human mammary cancer cells and cytolysis by natural killer cells [21]; repressed induced and constitutively expressed cyclooxygenase-2 (COX-2) in human lung cancer cells [22]. In exploring the anticancer activity of citrus flavonoids, another major PMF, nobiletin was found to have effectively inhibited the proliferation and migration of human umbilical endothelial cells of human prostate, skin, breast and colon carcinoma cell lines [23]; reduced AOM-induced cell proliferation in colonic adenocarcinoma cells [24]; suppressed the proliferation, migration and tube formation on matrigel of human umbilical vein endothelial cells stimulated with endothelial cell growth supplement [25]; and attenuated the growth of prostate cancer cells and reduced azoxymethane (AOM)-induced large bowel carcinogenesis in rats [26], to name a few. Multiple biological pathways of anti-cancer mode of action by citrus flavonoids were also studied and summarized [27]. Furthermore, the study of structure activity relationship (SAR) of citrus flavonoids and cancer prevention was linked to the structural similarities between flavonoids and 17β-estradiol, suggesting interaction of flavonoids with estrogen receptors and also with estrogen metabolizing enzymes, such as cytochrome P450 enzymes CYP1A1 and CYP1B1, which are over-expressed in variety of tumor tissues [28].