Moderate-dose Regular Lifelong Alcohol Intake Changes the Intestinal Flora, Protects against Aging, and Keeps Spatial Memory in the Senescence-accelerated Mouse Prone 8 (SAMP8) Model

• Published in: Journal of pharmacy & pharmaceutical sciences Vol. 19; no. 4; pp. 430 - 447
• Main Authors: Shimizu, Chikako, Oki, Yasuhiro, Mitani, Yutaka, Tsuchiya, Youichi, Nabeshima, Toshitaka
• Format: Journal Article
• Language: English
• Published: Canada Frontiers Media S.A 03.11.2016
• Subjects: Aging - drug effects; Animals; Ethanol - administration & dosage; Ethanol - pharmacology; Gastrointestinal Microbiome - drug effects; Male; Mice; Models, Animal; Protective Agents - administration & dosage; Protective Agents - pharmacology; Spatial Memory - drug effects
• ISSN: 1482-1826; 1482-1826
• DOI: 10.18433/j3990v

Heavy and long-term alcohol consumption increase the risk of alcohol-related diseases. Epidemiological studies show moderate drinking reduces the risk of mortality, cardiovascular diseases, and brain infarction in the J-shaped or U-shaped curve effect. However, why moderate drinkers may be healthy and non-drinkers may be ill in diverse populations remains controversial. Herein, we examined the relationship between moderate/lifelong alcohol intake and aging, especially aging-related cognitive functions in senescence-accelerated mouse prone 8 (SAMP8) model.  Methods: SAMP8 model (5-week-old, male, n = 36), a model of age-related cognitive deficit, were group-housed (n = 6/cage) and provided free access to water (water group, n = 18) or 1% ethanol (EtOH group, n = 18, intake started when mice were 9 weeks old). The object recognition test (ORT) and object location test (OLT) were used to evaluate cognitive functions. The intestinal flora at the age of 87 weeks was analyzed by terminal restriction fragment length polymorphism (T-RFLP).  The lifespan of the EtOH-group mice was about 4 weeks longer than that of the water-group mice. In the EtOH group, spatial recognition impairment, assessed by OLT, was observed later (age, 73 weeks) than that in the water group (age, 52 weeks). The spinal curvature and skin conditions progressed significantly slower in the EtOH group than in the water group. Moreover, diarrhea symptoms only appeared in the water group, at the age of 82 weeks. The T-RFLP analysis of the intestinal flora indicated higher Lactobacillales order and lower Clostridium cluster XI in the EtOH group than in the water group, although those were extremely high in some mice close to death in both groups. Water-group mice with diarrhea presented significantly higher Clostridium cluster XI than did those without diarrhea (P = 0.017).  Moderate alcohol intake changes intestinal flora and positively affects aging of SAMP8 model.