Mechanisms of lifespan extension and preventive effects of calorie restriction on tumor development: Possible link between central neuroendocrine system and peripheral metabolic adaptation
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- Chiba Takuya
- Biomedical Gerontology Laboratory, Faculty of Human Sciences, Waseda University Institute of Applied Brain Sciences, Waseda University
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- Dong Kesu
- Biomedical Gerontology Laboratory, Faculty of Human Sciences, Waseda University
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- Nishizono Shoko
- Faculty of Biotechnology and Life Science, Sojo University
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- Shimokawa Isao
- Investigative Pathology, Graduate School of Biomedical Sciences, Nagasaki University
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Abstract
Restriction of food intake (calorie restriction [CR]) in laboratory animals extends their lifespan and delays the onset of various age-associated diseases, including cancer development. Recent studies revealed that the molecular mechanisms underlying CR-mediated anti-aging effects may be regulated by a confined number of signal transduction pathways that are triggered by neuropeptide Y (NPY) neurons in the neuroendocrine system. On the other hand, possible peripheral regulators of the beneficial effects of CR involve a transcriptional regulator complex, the hepatocyte nuclear factor 4α/peroxisome proliferator-activated receptor gamma coactivator 1-α (HNF-4α/PGC-1α) complex. This complex could regulate not only glucose and lipid metabolism, but also DNA damage responses in the liver. Therefore, maintenance of optimal glucose and lipid levels to prevent metabolic syndrome, and activation of the DNA damage response for suppression of tumor development, may depend on the HNF-4α/PGC-1α complex. Hence, small molecules modulating the activity of this complex could be an important target for development of CR mimetics (CRM), which mimic the beneficial effects of CR without actual food restriction.
Journal
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- The Journal of Physical Fitness and Sports Medicine
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The Journal of Physical Fitness and Sports Medicine 2 (3), 259-266, 2013
The Japanese Society of Physical Fitness and Sports Medicine
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Details 詳細情報について
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- CRID
- 1390282680393456768
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- NII Article ID
- 10031179347
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- NII Book ID
- AA12573156
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- ISSN
- 21868123
- 21868131
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- NDL BIB ID
- 024738003
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed