The predictive effect of cardiorespiratory fitness (CRF) on brain aging in normal condition versus obesity‐induced premature aging.

Background: Previous studies demonstrated that CRF predicts brain aging as indicated by higher brain volume, greater white matter integrity, and lower risk of dementia mortality in people with higher CRF level. However, mechanisms that mediate the predictive effect of CRF on brain aging have never been holistically determined in both normal condition and obesity‐induced premature aging. Method: Seven‐week‐old male Wistar rats received either a normal diet (ND; n=6) or a high‐fat diet (HFD; n=6) for 28 weeks. At week 12 and 28, rats were run on a treadmill to measure CRF level, and fasting blood was also collected for metabolic parameters. At week 28, open field, novel object location, and novel object recognition tests were conducted. At the end of week 28, brain tissues were then obtained after sacrifice. Result: From week 12 to 28, all rats developed aging as indicated by decreased CRF level, insulin resistance, and dyslipidemia. Compared to ND‐fed rats, HFD‐fed rats exhibited obesity‐induced premature brain aging as indicated by mitochondrial dysfunction, increased oxidative stress and inflammation, increased apoptosis, blood brain barrier breakdown, synaptic dysfunction, impaired neurogenesis, increased Alzheimer's disease markers, and cognitive dysfunction. In both groups of rats, CRF level at week 12 revealed positive correlations with several brain parameters at week 28, including metabolism, mitochondrial fusion, autophagy, antioxidative capacity, synapse, and neurogenesis, while a negative correlation between CRF level at week 12 and brain oxidative stress at week 28 was observed (Table 1). Only in ND‐fed rats, CRF level at week 12 was negatively correlated with brain apoptosis and anxiety‐like behavior at week 28 (Table 1). Only in HFD‐fed rats, CRF level at week 12 was positively correlated with brain insulin signaling, mitophagy, blood brain barrier, and cognition at week 28, whereas there was a negative correlation between CRF level at week 12 and Alzheimer's disease markers at week 28 (Table 1). Conclusion: High CRF level attenuates aging‐induced brain pathology, resulting in mitigating cognitive impairment. Interestingly, these effects of CRF become highly potent in obesity‐induced premature aging since greater number of brain parameters that correlated with CRF level was observed in HFD‐fed rats. [ABSTRACT FROM AUTHOR]