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Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria
- Source :
- Aging (Albany NY)
- Publication Year :
- 2016
- Publisher :
- Impact Journals LLC, 2016.
-
Abstract
- Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased. Dietary restriction (DR) caused accumulation of TERT protein in mouse brain mitochondria correlating to decreased ROS release and improved learning and spatial short-term memory. Decreased mTOR signalling is a mediator of DR. Accordingly, feeding mice with rapamycin increased brain mitochondrial TERT and reduced ROS release. Importantly, the beneficial effects of rapamycin on mitochondrial function were absent in brains and fibroblasts from first generation TERT -/- mice, and when TERT shuttling was inhibited by the Src kinase inhibitor bosutinib. Taken together, our data suggests that the mTOR signalling pathway impinges on the mitochondrial localisation of TERT protein, which might in turn contribute to the protection of the brain by DR or rapamycin against age-associated mitochondrial ROS increase and cognitive decline.
- Subjects :
- 0301 basic medicine
Mitochondrial ROS
Telomerase
DNA damage
brain
Mitochondrion
Biology
medicine.disease_cause
telomerase
03 medical and health sciences
Mice
0302 clinical medicine
Nitriles
medicine
Animals
PI3K/AKT/mTOR pathway
Genetics
chemistry.chemical_classification
Mice, Knockout
Sirolimus
Reactive oxygen species
Aniline Compounds
rapamycin
TOR Serine-Threonine Kinases
aging
dietary restriction
Cell Biology
Telomere
Cell biology
Mitochondria
Oxidative Stress
030104 developmental biology
src-Family Kinases
chemistry
Quinolines
Reactive Oxygen Species
030217 neurology & neurosurgery
Oxidative stress
Research Paper
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19454589
- Volume :
- 8
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Aging (Albany NY)
- Accession number :
- edsair.doi.dedup.....343b5bdc00f5f287f14bc161af4ceadc