Alternate-day fasting reverses the age-associated hypertrophy phenotype in rat heart by influencing the ERK and PI3K signaling pathways

作者：Castello Laura; Maina Marco; Testa Gabriella; Cavallini Gabriella; Biasi Fiorella; Donati Alessio; Leonarduzzi Gabriella; Bergamini Ettore; Poli Giuseppe; Chiarpotto Elena^*

来源：Mechanisms of Ageing and Development, 2011, 132(6-7): 305-314.

DOI：10.1016/j.mad.2011.06.006

• Alternate-day fasting
• Heart
• Hypertrophy
• PI3K
• ERK

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 PI3K gamma. 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 PI3K gamma 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.

• 出版日期2011-7