Life-long caloric restriction: Effect on age-related changes in motoneuron numbers, sizes and apoptotic markers

The first purpose of this study was to determine the effect of advanced age (31 months) on the number of motoneurons in the lumbar enlargement of the rat and to determine if motoneurons die via apoptosis with age. The second purpose was to determine if caloric restriction (CR) would attenuate any observed age-related changes in motoneuron numbers or markers of apoptosis and ROS damage. Using immunohistochemistry to identify choline acetyltransferase (ChAT) – positive motoneurons in the ventro-lateral horn larger than 15 μm in diameter and having a clear soma and nucleus were sized and counted. Western blots were used to quantify markers of ROS, apoptosis and autophagy in the ventral horn of the lumbar enlargement. The results suggest that the total number of motoneurons in the rat lumbar enlargement does not significantly decrease with age. Also at the time of sacrifice, aged motoneurons were actively undergoing apoptosis through the intrinsic pathway, in a caspase-dependent manner. CR was able to attenuate the increase in body weight, body weight/muscle mass ratio and the level of activate caspase-3 associated with age. CR also reduced the level of heat shock protein 27, oxoguanine glycosylase 1, cytochrome c and LC3B-I.

Research highlights▶ The overall number of lumbar motoneurons does not decrease with age. ▶ No preferential loss of motoneurons based on size occurs with age. ▶ Old motoneurons die via apoptosis in a caspase-dependent manner. ▶ Caloric restriction down-regulates Hsp27, OGG1 and cytochrome c in old motoneurons.