Behavioural Brain Research 315 (2016) 45–50 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Long-term caloric restriction in mice may prevent age-related learning impairment via suppression of apoptosis Lina Ma a,b , Rong Wang (M.D. Ph.D.) b,∗ , Wen Dong b , Yun Li a , Baolei Xu a , Jingshuang Zhang b , Zhiwei Zhao b a Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China b Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing 100053, China h i g h l i g h t s • CR can prevent age-related learning impairments. • CR increased the expressions of Bcl-2 protein and mRNA and decreased the expression of Bax, Caspase-3 and PARP protein. • Long-term CR may prevent age-related learning impairments via suppressing apoptosis. a r t i c l e i n f o Article history: Received 10 April 2016 Received in revised form 15 July 2016 Accepted 20 July 2016 Available online 21 July 2016 Keywords: Caloric restriction Learning ability Apoptosis Ageing a b s t r a c t Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related dis- orders in various species from yeast to rodents. However, the underlying mechanisms have not yet been clearly defined. Therefore, we aimed to identify the underlying mechanisms of long-term CR on age-related learning impairment in C57/BL mice. Thirty six-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n = 10), high energy group (HE group, n = 10), and CR group (n = 10). After 10 months, the Morris water maze test was performed to monitor learning abilities. Western blotting, immunohistochemistry and real-time polymerase chain reaction were used to monitor changes in protein and mRNA levels associated with apoptosis-related proteins in the hip- pocampus. The average escape latency was lower in the CR group compared with the NC group, and the average time taken to first cross the platform in the CR group was significantly shorter than the HE group. Both Bcl-2 protein and mRNA expression levels in the CR group were significantly higher than those of the NC group and HE group. The expression of Bax, Caspase-3 and PARP protein in the CR group was significantly lower than the NC group. Our findings demonstrate that long-term CR may prevent age-related learning impairments via suppressing apoptosis in mice. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Caloric restriction (CR) is defined as limiting calorie intake com- pared to baseline unrestricted or ad libitum (AL) consumption, with maintained levels of vitamins, minerals, or other essential biomolecules [1]. McCay et al., showed that CR in rodents could markedly extend lifespan [2,3], and many researchers have shown that CR results in a multitude of health benefits in humans [4], including increased insulin sensitivity, and reduced levels of proin- ∗ Corresponding Author at: Central Laboratory Xuan Wu Hospital, Capital Medical University #45 Changchun Street, Xicheng District, Beijing 100053, China. E-mail address: rong wang72@aliyun.com (R. Wang). flammatory cytokines, reactive oxygen species, and atherosclerotic lipids in the blood [5,6].To date, CR is the only non-genetic inter- vention that reliably increases life span and health across multiple organisms [7], however, the molecular mechanisms are not well understood. Alzheimer’s disease (AD) is an age-related neurodegenerative disorder with a complex etiology [8], and is characterized by impaired learning, memory, and executive function [9]. Clinical manifestations of AD are closely associated with the formation of senile plaques and neurofibrillary tangles, neuronal loss and cognitive decline [10]. Aging is a complex physiological process caused by accumulation of damage at the molecular, cellular, and organ level [11], and apoptosis plays an essential role. Various fac- tors such as Bcl-2, Bax, caspases, and amyloid beta (A), lead to http://dx.doi.org/10.1016/j.bbr.2016.07.036 0166-4328/© 2016 Elsevier B.V. All rights reserved.