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Published on: October 23, 2018
Targeting mTOR for Anti-Aging and Anti-Cancer Therapy
1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, the Joint International Research Laboratory of Metabolic & Developmental Sciences MOE, Shanghai Jiao Tong University, Shanghai 200240, China.
Abstract:
The balance between anabolism and catabolism is disrupted with aging, with the rate of anabolism being faster than that of catabolism. Therefore, mTOR, whose major function is to enhance anabolism and inhibit catabolism, has become a potential target of inhibition for anti-aging therapy. Interestingly, it was found that the downregulation of the mTOR signaling pathway had a lifespan-extending effect resembling calorie restriction. In addition, the mTOR signaling pathway promotes cell proliferation and has been regarded as a potential anti-cancer target. Rapamycin and rapalogs, such as everolimus, have proven to be effective in preventing certain tumor growth. Here, we reviewed the basic knowledge of mTOR signaling, including both mTORC1 and mTORC2. Then, for anti-aging, we cited a lot of evidence to discuss the role of targeting mTOR and its anti-aging mechanism. For cancer therapy, we also discussed the role of mTOR signaling in different types of cancers, including idiopathic pulmonary fibrosis, tumor immunity, etc. In short, we discussed the research progress and both the advantages and disadvantages of targeting mTOR in anti-aging and anti-cancer therapy. Hopefully, this review may promote more ideas to be generated for developing inhibitors of mTOR signaling to fight cancer and extend lifespan.
Insights
Targeting the mTOR signaling pathway may extend lifespan and fight cancer. Inhibiting mTOR shows promise for anti-aging and anti-cancer therapies by modulating anabolic and catabolic processes.
Area of Science:
- Biochemistry
- Cell Biology
- Gerontology
Background:
- Aging disrupts the balance between anabolism and catabolism.
- The mTOR signaling pathway regulates these processes and is implicated in aging and cancer.
- mTORC1 and mTORC2 are key components of this pathway.
Purpose of the Study:
- To review the role of mTOR signaling in aging and cancer.
- To discuss the mechanisms of mTOR inhibition for anti-aging and anti-cancer therapies.
- To explore the advantages and disadvantages of targeting mTOR.
Main Methods:
- Literature review of mTOR signaling pathways.
- Analysis of evidence for mTOR's role in aging and cancer.
- Discussion of mTOR inhibitors like rapamycin and rapalogs.
Main Results:
- Downregulation of mTOR signaling extends lifespan, mimicking calorie restriction.
- mTOR pathway activity is linked to cell proliferation and tumor growth.
- mTOR inhibitors show efficacy in preclinical cancer models.
Conclusions:
- Targeting mTOR signaling offers a dual approach for anti-aging and anti-cancer strategies.
- Further research into mTOR inhibitors could yield novel therapeutics.
- Understanding mTOR's complex role is crucial for optimizing its therapeutic potential.
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