Nat cell biol: how does cell aging inhibit and promote cancer?

February 24, 2019 / BIOON / - researchers from the Westar Institute in the United States have revealed a new function of nicotinamide adenine dinucleotide (NAD) metabolism in the process of aging cells releasing tumor promoting molecules Relevant research results were recently published in nature cell In biology, the study also warned that it should be used more precisely, given the potential for carcinogenic side effects of supplements that enhance NAD +, which are currently being developed as anti-aging nutritional supplements Photo source: Nat cell biol cell senescence is a process in which cells stop dividing irreversibly, and it also represents a powerful mechanism of inhibiting cancer At the same time, senescent cells also produce a series of soluble inflammatory factors to promote the growth of cancer This effect is called the senescence associated secret phenotype (SASP) Dr rugang Zhang, deputy director of cancer center, Professor of gene expression and regulation project group, and co leader of Westar Institute, studied the role of a class of proteins called hmgas in cell aging and SASP Hmgas is a kind of DNA binding protein, which can regulate gene expression Over expression of hmgas in many kinds of tumors is related to poor prognosis of patients, and they can also promote aging This new study aims to uncover the mechanism by which protein members of the HMGA family play a dual role in cancer Zhang and his colleagues found that hmgas in aging cells increased the content of Nampt, a key protein for NAD +, a cytokine important for metabolism and enzyme function It is important that an increase in NAD + levels also enhances SASP "Our data show that NAD + levels affect the secretory activity of senescent cells in a way that may promote tumor progression." Zhang said "It has been known that the concentration of NAD + in cells will decrease during the aging process, so the supplement of NAD + is being paid attention and explored by scientists as a new method to prevent aging and aging related diseases Our results may have a profound impact on this area " In fact, by manipulating the expression of HMGA1 and Nampt, the researchers found that the increased metabolism of NAD + promoted the proliferation and progression of tumor cells in mouse pancreatic and ovarian cancer models These data suggest that increased expression of HMGA1 and NAPT promotes high levels of SASP, enhances the inflammatory environment surrounding the tumor, and ultimately stimulates tumor growth "Our data suggest a possible anti-cancer strategy: targeting Nampt may be an effective strategy to inhibit the proinflammatory and tumor microenvironment in tumors with high expression of HMGA1 that are undergoing anti-aging cancer treatment (such as chemotherapy and radiotherapy)." Timothy nacarelli, Ph.D., a postdoctoral researcher at Zhang laboratory and the first author of the study, said "Nampt inhibitors are currently in clinical trials, so they are easily available for use in these new areas." Reference materials: Timothy nacarelli et al NAD + metadata governs the proinflammatory sense associated secret, Nature Cell Biology (2019) Doi: 10.1038/s41556-019-0287-4