A new way to fight aging and cancer?
It has long been known that cancer is a disease associated with aging, but the molecular relationship between these two phenomena has remained a mystery until now. In their latest work, researchers at the Cancer Research Center at Thomas Jefferson University, working under the guidance of Professor Michael P. Lisanti, demonstrated that physiological aging (loss of the ability of aging cells to divide) and autophagy (self-destruction of cells by digesting their own structures) of the fibroblasts surrounding the tumor are essentially two sides of the same medals also act as a source of "food" that ensures the growth and metastasis of malignant tumors.
Previously, the authors found that malignant tumors induce autophagy of surrounding healthy cells as a reaction to oxidative stress. The cells that die as a result serve as a food source for the growing tumor.
In the last work, they showed that the cells of the tumor environment entering the phase of physiological aging demonstrate many characteristics of autophagic cells. In other words, they also serve as food for tumors. Thus, it turns out that the aging process practically "feeds" the tumor.
Since the physiological aging of cells is considered a reflection of the biological aging of the body, the data obtained can serve as an explanation for the fact that the probability of developing cancer increases rapidly in old age.
To verify the revealed relationship, scientists have developed a genetically tracked model system for directly studying the role of autophagy in tumor growth and metastasis. First, they took human fibroblasts, immortalized by activating the telomerase enzyme, and embedded in their DNA the genes of proteins involved in the autophagy process. After that, they confirmed that the resulting cells show signs of mitophagy ("devouring" their own mitochondria) and a shift towards aerobic glycolysis, accompanied by an increase in the synthesis of lactic acid and ketones. All these signs correspond to the behavior of the fibroblasts surrounding the tumor. In animal experiments, they demonstrated that when co-administered with human breast cancer cells, the resulting autophagic fibroblasts increase metastasis activity by more than 10 times.
Based on the data obtained, the researchers suggested that the rate of metastasis is largely determined not by the cancer cells themselves, but by the aging fibroblasts surrounding them. This hypothesis completely changes the understanding of cancer as a disease. She questions the well-established notion that cancer is an autonomous genetic disease of cells. Apparently, cancer is a true disease of aging, which provides the tumor with nutrients necessary for growth and metastasis.
Based on the new data, in order to stop the growth and metastasis of the tumor, it is necessary to deprive it of the nutrition provided by dying aging cells. This can be done by suppressing the mechanisms of autophagy and physiological aging of tumor microenvironment cells.
However, experts hope that the destruction and prevention of the formation of tumors and other age-related diseases will only be a side effect of the drugs, the basis for the development of which will be the data obtained. The main result of their use will be a slowdown in the aging process.
Articles CTGF drives autophagy, glycolysis, and senescence in cancer associated fibroblasts via HIF1 activation, metabolically promoting tumor growth, Autophagy and senescence in cancer-associated fibroblasts metabolically supports tumor growth and metastasis, via glycolysis and ketone production, Two-compartment tumor metabolism: Autophagy in the tumor microenvironment, and oxidative mitochondrial metabolism (OXPHOS) in cancer cells and Cancers co-opt cohabitants’ catabolism: Autophagy and senescence in the tumor stroma. published in the journal Cell Cycle (Volume 11, Issue 12).
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ScienceDaily:
How Aging Normal Cells Fuel Tumor Growth and Metastasis19.06.2012