Mechanisms of ageing and development
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In the present study, we investigated whether mild-intensity physical exercise represents a successful strategy to enhance spatial learning and memory and hippocampal plasticity in aging rats, as previously described for long-term exposure to running wheel or treadmill exercise. Aging Wistar rats were submitted to short bouts (4-6 min) of exercise treadmill during five consecutive weeks. ⋯ Remarkably, the observed cognitive-enhancing properties of short bouts of exercise were accompanied by the activation of serine/threonine protein kinase (AKT) and cAMP response element binding (CREB) pro-survival signaling that culminates in the marked increase on the brain-derived neurotrophic factor (BDNF) mRNA expression and BDNF protein levels on the hippocampus of aging rats. Altogether, these results indicate that short bouts of exercise represent a viable behavioral strategy to improve cognition and synaptic plasticity in aging rats which should be taken into account in further studies addressing the effects of physical exercise in aging subjects.
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A balanced diet reduces the risk of life-threatening diseases such as diabetes and cancer. A reduced supply of energy at the cellular level leads to an increased concentration of AMP, which, in turn, results in LKB1-mediated activation of the AMPK kinase. The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK. ⋯ Furthermore, p53 activation by AICAR was blocked by rapamycin, a specific inhibitor of the mTOR kinase, which is a crucial regulator of cell growth. Rapamycin did not block p53 activation by resveratrol, which, in contrast to AICAR, induced the DNA damage response, senescence-like growth inhibition, a high level of post-translational modification of p53, and weak upregulation of MDM2 (the negative regulator of p53). Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.