Loss in oxidative stress tolerance with aging linked to reduced extracellular signal-regulated kinase and Akt kinase activities
| Autor: | Xiantao Wang, Sonsoles Shack, Shizuo Ikeyama, Gertrude C. Kokkonen, Nikki J. Holbrook |
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| Rok vydání: | 2001 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Aging Proto-Oncogene Proteins c-akt Cell Survival media_common.quotation_subject Morpholines Biology Protein Serine-Threonine Kinases medicine.disease_cause Biochemistry Models Biological Internal medicine Proto-Oncogene Proteins Genetics medicine Extracellular Animals Enzyme Inhibitors Molecular Biology Protein kinase B Cells Cultured media_common Flavonoids Kinase Longevity Drug Synergism Hydrogen Peroxide Oxidants Rats Oxidative Stress Endocrinology Apoptosis Chromones Immunology Hepatocytes Mitogen-Activated Protein Kinases Energy Intake Oxidative stress Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 16(1) |
| ISSN: | 1530-6860 |
| Popis: | Oxidative stress is believed to be an important factor in the development of age-related diseases, and studies in lower organisms have established links between oxidative stress tolerance and longevity. We have hypothesized that aging is associated with a reduced ability to mount acute host defenses to oxidant injury, which increases the vulnerability of aged cells to stress. We tested this hypothesis by using primary hepatocytes from young (4-6 months) and aged (24-26 months) rats. Old hepatocytes were more sensitive to H2O2-induced apoptosis than were young cells. Lower survival is associated with reduced activations of extracellular signal-regulated kinase (ERK) and Akt kinase, both of which protect against oxidant injury. That reduced ERK and Akt activities contribute to lower survival of aged cells was supported by additional findings. First, pharmacologic inhibition of ERK and Akt activation in young cells markedly increased their sensitivity to H2O2. Second, caloric restriction, which increases rodent life span and delays the onset of many age-related declines in physiologic function, prevented loss in ERK and Akt activation by H2O2 and enhanced survival of old hepatocytes to levels similar to those of young cells. Strategies aimed at boosting these host responses to acute oxidant injury could have significant anti-aging benefits. |
| Databáze: | OpenAIRE |
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