Effects of graded calorie restriction: XXII. Impact of long-term graded calorie restriction on tissue partitioning, digestive efficiency, bone health, and coordination in male C57BL/6J mice

Calorie restriction (CR) is the reduction in calorie intake while avoiding malnutrition. CR increases longevity and attenuates the development of many age-related diseases, although some unfavorable responses have been reported. In response to CR, energy is withdrawn from tissues to correct the energy deficit. Changes in tissue mass over short-term, 3 months graded CR (STCR) were complex and while most tissues reduced size, some grew. Employing a graded long-term CR (LTCR) protocol in male C57BL/6J mice, tissue utilization, digestive efficiency, bone health and motor coordination was investigated. Mice were restricted by 10%-40% over 580 days/19 months and sacrificed at 24-month old. Control mice fed ad libitum in the 12-hr darkphase only (12AL) were regarded as 0CR. The patterns of tissue weights, digestive efficiency, and bone measurements across the levels of CR were consistent between the STCR and LTCR studies, highlighting shared similarities over both experiments. Notable differences were enhanced utilization of the reproductive accessory organs which could be linked to a shutdown of the reproductive axis; reduced utilization of the spleen, changes in the hierarchy of investment in the digestive organs which was not linked to digestive efficiency. The vital organs were protected from utilization, with preservation of the brain by CR, presumably linked to reduced neurodegeneration and sustained coordination. The favorable effects of LTCR on bone health contradict previous negative reports. Overall, morphological changes determined within 3 months of CR, persisted to 19 months. The pattern of tissue utilization may be critical to the beneficial effects of CR.