The impact of age and frailty on ventricular structure and function in C57BL/6J mice.

KEY POINTS: Heart size increases with age (called hypertrophy), and its ability to contract declines. However, these reflect average changes that may not be present, or present to the same extent, in all older individuals. That aging happens at different rates is well accepted clinically. People who are aging rapidly are frail and frailty is measured with a 'frailty index'. We quantified frailty with a validated mouse frailty index tool and evaluated the impacts of age and frailty on cardiac hypertrophy and contractile dysfunction. Hypertrophy increased with age, while contractions, calcium currents and calcium transients declined; these changes were graded by frailty scores. Overall health status, quantified as frailty, may promote maladaptive changes associated with cardiac aging and facilitate the development of diseases such as heart failure. To understand age-related changes in heart structure and function, it is essential to know both chronological age and the health status of the animal. ABSTRACT: On average, cardiac hypertrophy and contractile dysfunction increase with age. Still, individuals age at different rates and their health status varies from fit to frail. We investigated the influence of frailty on age-dependent ventricular remodelling. Frailty was quantified as deficit accumulation in adult (≈7 months) and aged (≈27 months) C57BL/6J mice by adapting a validated frailty index (FI) tool. Hypertrophy and contractile function were evaluated in Langendorff-perfused hearts; cellular correlates/mechanisms were investigated in ventricular myocytes. FI scores increased with age. Mean cardiac hypertrophy increased with age, but values in the adult and aged groups overlapped. When plotted as a function of frailty, hypertrophy was graded by FI score (r = 0.67-0.55, P < 0.0003). Myocyte area also correlated positively with FI (r = 0.34, P = 0.03). Left ventricular developed pressure (LVDP) plus rates of pressure development (+dP/dt) and decay (-dP/dt) declined with age and this was graded by frailty (r = -0.51, P = 0.0007; r = -0.48, P = 0.002; r = -0.56, P = 0.0002 for LVDP, +dP/dt and -dP/dt). Smaller, slower contractions graded by FI score were also seen in ventricular myocytes. Contractile dysfunction in cardiomyocytes isolated from frail mice was attributable to parallel changes in underlying Ca2+ transients. These changes were not due to reduced sarcoplasmic reticulum stores, but were graded by smaller Ca2+ currents (r = -0.40, P = 0.008), lower gain (r = -0.37, P = 0.02) and reduced expression of Cav1.2 protein (r = -0.68, P = 0.003). These results show that cardiac hypertrophy and contractile dysfunction in naturally aging mice are graded by overall health and suggest that frailty, in addition to chronological age, can help explain heterogeneity in cardiac aging.

Effects of vitamin D levels on asthma control and severity in pre-school children.

OBJECTIVE: Prevalence of asthma and vitamin D deficiency has been increasing and leading to significant morbidities. This study aimed to compare the vitamin D levels in the pre-school children with asthma and in healthy controls and to assess the relationship between vitamin D levels and asthma clinical parameters and control. PATIENTS AND METHODS: Vitamin D [25(OH)D3] levels were measured in 102 pre-school children, aged 1-4 years with asthma and 102 healthy controls in winter. The patients with asthma were grouped according to serum vitamin D levels as sufficient, insufficient and deficient. Asthma control was classified according to the Global Initiative for Asthma (GINA) guidelines and the Test for Respiratory and Asthma Control in Kids (TRACK) in 1-4 years-old children. RESULTS: Serum vitamin D levels were 22.64 (9.96) ng/ml in the asthma group and 32.11 (14.74) ng/ml in the control group (p = 0.001). Total number of exacerbations during the previous year were significantly lower in the vitamin D sufficient group, compared to the deficient and insufficient groups (p = 0.03). Frequency of patients with controlled asthma was higher in the sufficient group compared to the deficient and insufficient groups (p = 0.001 and p = 0.001, respectively). There was a positive correlation between serum vitamin D levels and asthma control. CONCLUSIONS: The frequency of vitamin D deficiency and insufficiency was higher in children with asthma, compared to the controls. Therefore, we suggest that lower levels of vitamin D are associated with poor asthma control and increased asthma severity.