RESUMEN
Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic glucose output in wild type mice. In contrast, aged SIRT6-transgenic mice preserve hepatic glucose output and glucose homeostasis through an improvement in the utilization of two major gluconeogenic precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic gluconeogenic gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging.
Asunto(s)
Metabolismo Energético/genética , Fragilidad/metabolismo , Envejecimiento Saludable/metabolismo , Longevidad/genética , Sirtuinas/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Fragilidad/genética , Regulación de la Expresión Génica/fisiología , Gluconeogénesis/genética , Glucosa/metabolismo , Envejecimiento Saludable/genética , Humanos , Hígado/metabolismo , Masculino , Ratones , Ratones Transgénicos , Sirtuina 1/genética , Sirtuina 1/metabolismo , Sirtuinas/genéticaRESUMEN
This study investigated the effect of the listener's experience on the evaluation of intonation contours produced by hearing-impaired children. Stimuli included imitations of intonation (based on synthetic speech stimuli) produced by hearing-impaired children. Twenty listeners (10 experienced and 10 naive) evaluated the intonation production by means of two evaluation tools: a rating scale and a forced-choice test. No significant differences were found between the two listener groups using the forced-choice test, either for the falling or for the rising contours. However, a significant difference was found between the two listener groups using the rating scale, with regard to both the rising and the falling contours. Thus, the effect of experience decreased when using the forced-choice procedure. This finding supports the use of the forced-choice method for providing a perceptual measure of speech production performance that is independent of the listener's experience.
