The Study

Caloric restriction has been shown to increase the life span and health span of a broad range of species. A widely accepted cause of the functional losses that accompany aging is decreased brain metabolic and vascular functions. Therefore, preserving brain metabolism (i.e., glucose oxidative capacity) and hemodynamics are critical for optimizing health span. The authors studied the caloric restricted changes of brain metabolic and vascular functions in aging rats.

Methods

As ketone bodies are the alternative fuel substrate in the brain when glucose utilization goes down, the study examined concentration of ketone bodies, BHB and the effect on cerebral blood flow and metabolic and vascular functions. Blood samples were used to measure blood ketone bodies level of each rat.

Results

The study found that ketone bodies BHB were significantly elevated in the caloric restriction group of rats. The study demonstrated that caloric restriction increases the level of ketone bodies and preserves cerebral blood flow in aging rats. Preserved metabolic and vascular functions were observed both globally and regionally including in the cortex, hippocampus, and hypothalamus. Because neuronal transmission and levels of ketone bodies are highly associated with cerebral blood flow, and the study observed preserved cerebral blood flow, it suggests that caloric restriction can preserve brain metabolism, neuronal activity, and cerebral blood flow and thus slow cognitive decline in aging.

Conclusion

In relation to ketone bodies and aging, the authors conclude that “the shift from glucose metabolism to ketone bodies’ utilization under caloric restriction is consistent with findings that ketone bodies are an alternative fuel for brain cells when glucose availability is insufficient; ketosis proportionally spares glucose utilization in the brain. Ketone bodies can support most, if not all, of basal (housekeeping) neuronal oxidative metabolism.” And further, “because both brain glucose utilization and neuronal activity decline during aging, the shifted metabolism from glucose to ketone bodies under caloric restriction may be able to sustain brain energy supply and functions in aging brain.”

Glucose consumption declines with age and in an accelerated manner in Alzheimer’s Disease. The shift from glucose metabolism to ketone bodies’ utilization “may also play an important role in preserving memory in aging since glucose plays a critical role in forming and enhancing memory. Without additional or alternative fuel substrates, it is not surprising that the ability for memory processing goes down with age and more significantly in Alzheimer’s Disease.” In conclusion, up-regulating ketone bodies metabolism, sustaining cerebral blood flow and a-KG may play a crucial role in preserving neuronal health span under caloric restriction. The authors suggest these results provide a rationale for caloric restriction-induced sustenance of brain health with extended life span.

Citation

Lin, A. L., Zhang, W., Gao, X., and Watts, L. (2015). Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain. Neurobiol. Aging 36, 2296–2303.