PUBLICATION
Dietary and Pharmacological Interventions that Inhibit Mammalian Target of Rapamycin (mTOR) Activity Alter the Brain Expression Levels of Neurogenic and Glial Markers in An Age- and Treatment-Dependent Manner
- Authors
- Celebi-Birand, D., Ardic, N.I., Karoglu Eravsar, E.T., Sengul, G.F., Kafaligonul, H., Adams, M.
- ID
- ZDB-PUB-200422-98
- Date
- 2020
- Source
- Rejuvenation Research 23(6): 485-497 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Aging/metabolism*
- Animals
- Autophagy/drug effects
- Biomarkers/metabolism
- Brain/drug effects
- Brain/metabolism*
- Fasting/metabolism*
- Female
- Male
- Neuroglia/drug effects
- Neuroglia/metabolism*
- Neurons/cytology*
- Neurons/drug effects
- Neurons/metabolism
- Sirolimus/pharmacology*
- TOR Serine-Threonine Kinases/antagonists & inhibitors*
- TOR Serine-Threonine Kinases/metabolism
- Zebrafish/metabolism*
- PubMed
- 32279604 Full text @ Rejuvenation Res.
Citation
Celebi-Birand, D., Ardic, N.I., Karoglu Eravsar, E.T., Sengul, G.F., Kafaligonul, H., Adams, M. (2020) Dietary and Pharmacological Interventions that Inhibit Mammalian Target of Rapamycin (mTOR) Activity Alter the Brain Expression Levels of Neurogenic and Glial Markers in An Age- and Treatment-Dependent Manner. Rejuvenation Research. 23(6):485-497.
Abstract
Intermittent fasting (IF) and its mimetic, rapamycin extend lifespan and healthspan through mechanisms that are not fully understood. We investigated different short-term durations of IF and rapamycin on cellular and molecular changes in the brains of young (6-10 months) and old (26-31 months) zebrafish. Interestingly, our results showed that IF significantly lowered glucose levels while increasing DCAMKL1 in both young and old animals. This proliferative effect of IF was supported by the upregulation of foxm1 transcript in old animals. Rapamycin did not change glucose levels in young and old animals but had differential effects depending on age. In young zebrafish, PCNA and the LC3-II/LC3-I ratio was decreased, whereas GFAP and gephyrin were decreased in old animals. The changes in proliferative markers and a marker of autophagic flux suggest an age-dependent interplay between autophagy and cell proliferation. Additionally, changes in glia and inhibitory tone suggest a suppressive effect on neuroinflammation but may push the brain towards a more excitable state. mTOR activity in the brain following the IF and rapamycin treatment was differentially regulated by age. Interestingly, rapamycin inhibited mTOR more potently in young animals than IF. PCA supported our conclusion that the regulatory effects of IF and rapamycin were age-specific, since we observed different patterns in the expression levels and clustering of young and old animals. Taken together, our results suggest that even a short-term duration of IF and rapamycin have significant effects in the brain at young and old ages, and that these are age- and treatment-dependent.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping