Examination of age-related changes in the submandibular glands of male mice.

Salivary gland hypofunction adversely affects the oral environment and daily life by causing dry mouth (xerostomia). Senescence-related atrophy of salivary gland tissues is one cause of xerostomia, and it is particularly common among the elderly. However, the underlying mechanism is poorly understood, and no treatment has been established. Therefore, we examined age-related changes in senescence-associated secretory phenotype (SASP) factors, which regulate stemness and cellular senescence, in mouse submandibular glands. We analyzed the submandibular glands of 6-week-old (young group, n = 6) and 82-week-old mice (aged group, n = 6). We performed salivary flow rate measurements, histological analysis including immunohistochemistry, and quantitative real-time PCR. The salivary flow rate was significantly lower in the aged group than in the young group. In addition, immunostaining and quantitative real-time PCR illustrated that aquaporin-5 and α-amylase expressions were significantly decreased in aged mice, indicating salivary gland hypofunction. c-Kit and cytokeratin 5 expressions were also significantly decreased in this group, suggesting that the regenerative abilities of the submandibular glands were reduced because of decreased stem and progenitor cell counts. Furthermore, the levels of p16INK4a and p21 (the senescence markers) and TGF-ß1 and IL-6 (SASP factors) were significantly increased in mice, suggesting that senescence had been promoted. The decreased numbers of stem and progenitor cells and increased levels of SASP factors might be associated with age-related changes in mouse submandibular glands. These results might facilitate the development of treatments for senescence-related submandibular gland hypofunction.

Association between nocturnal falls and hypnotic drug use in older patients at acute care hospitals.

PURPOSE: Although hypnotic drug use is a known risk factor for falls, few reports have analyzed fall risk associated with individual hypnotic drugs after adjusting for confounding factors. While it is recommended that benzodiazepine receptor agonists not be prescribed for older adults, it is unknown whether melatonin receptor agonists and orexin receptor antagonists are safe in this population. Here, we aimed to assess the influence of various hypnotic drugs on fall risk in older patients admitted to acute care hospitals. METHODS: We investigated the relationship between nocturnal falls and sleeping pill use in 8,044 hospitalized patients aged > 65 years. We used a propensity score matching method to homogenize characteristics of patients with and without nocturnal falls (n = 145 patients per group) using 24 extracted factors (excluding hypnotic drugs) as covariates. RESULTS: Our analysis of fall risk for each hypnotic drug revealed that benzodiazepine receptor agonists were the only drugs significantly associated with falls, suggesting that use of the drugs is a risk factor for falls in older adults (p = 0.003). In addition, a multivariate analysis of 24 selected factors, excluding hypnotic drugs, revealed that patients with advanced recurrent malignancies were at greatest risk of experiencing falls (OR: 2.62; 95% CI: 1.23-5.60; p = 0.013). CONCLUSION: Benzodiazepine receptor agonists should be avoided in older hospitalized patients since they increase fall risk, with melatonin receptor agonists and orexin receptor antagonists used instead. Particularly, fall risk associated with hypnotic drugs should be considered in patients with advanced recurrent malignancies.