title: Alternate-day fasting reverses the age-associated hypertrophy phenotype in rat heart by influencing the ERK and PI3K signaling pathways.
abstract: The age-related increased impedance in large arteries overloads the senescent heart, and the myocardial phenotype is hypertrophic. Together with qualitative changes observed in the senile heart, this can be responsible for impaired diastolic function. A restricted diet providing adequate nutrient intake, e.g. alternate-day fasting (ADF), has been shown to extend life-span and decrease incidence and progression of age-associated diseases in laboratory rodents, and to ameliorate some metabolic markers of aging in rhesus monkeys and humans. This study reports an age-related increase of some biological and morphological hypertrophy markers in the rat heart, together with increased plasma BNP, a well known marker of heart failure. The tissue modifications might likely be related to hyper-activation of two of the signaling pathways associated with myocardial pathological hypertrophy: ERK1/2 and PI3Kγ. Increased ERK1/2 activation might be in part related to the disturbance of STAT3, with a consequent decrease of SOCS3. In this context, the down-modulation of ERK1/2 and PI3Kγ signaling, together with the restoration of STAT3 activity and SOCS3 content, both observed with ADF, might help to reduce pathological hypertrophy stimuli and to rescue an important cardioprotective pathway, possibly opening new preventive and therapeutic perspectives in age-related heart failure.
authors: Pediatric Hospital Regina Margherita-S. Anna, Pediatric Oncohematology, Stem Cell Transplant and Cellular Therapy Centre, P.zza Polonia 94, 10126 Torino, Italy. laura.castello@unito.it
authors: Laura
authors: L
authors: Castello
authors: Marco
authors: M
authors: Maina
authors: Gabriella
authors: G
authors: Testa
authors: Gabriella
authors: G
authors: Cavallini
authors: Fiorella
authors: F
authors: Biasi
authors: Alessio
authors: A
authors: Donati
authors: Gabriella
authors: G
authors: Leonarduzzi
authors: Ettore
authors: E
authors: Bergamini
authors: Giuseppe
authors: G
authors: Poli
authors: Elena
authors: E
authors: Chiarpotto
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D005215:Fasting / Q000378:metabolism*; D008136:Longevity; D020935:MAP Kinase Signaling System; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050796:STAT3 Transcription Factor; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D019869:Phosphatidylinositol 3-Kinases; D048052:Mitogen-Activated Protein Kinase 3