Skeletal Muscle PGC-1β Signaling is Sufficient to Drive an Endurance Exercise Phenotype and to Counteract Components of Detraining in Mice

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy

A prospective examination of perceived stress as a mediator of the relationship between life-events and QOL following breast cancer

Objectives: This study prospectively investigated the relationship between life-events, perceived stress, and quality of life (QOL) following breast cancer diagnosis, using the bio-behavioural model of cancer stress as a framework. Design: A longitudinal, self-report design was used. Methods: Three waves of data from 10,543 mid-aged Australian women (aged 45-50 at Survey 1) were collected over 5 years as part of a population-based survey. From this group a subsample (N=140) were identified who did not have breast cancer at Survey 1, but who subsequently developed breast cancer. Random regression growth curve analyses were used to investigate whether perceived stress mediated the relationship between initial life-events and change in QOL functioning overtime. Results: Prospective evidence was generated for each of the three criteria for testing mediation. As the number of life-events before breast cancer increased, women were significantly more likely to experience corresponding increases in perceived stress over the 5-year period. As the level of perceived stress before breast cancer increased, women were more likely to experience deteriorations overtime in role emotional, role physical, vitality, bodily pain, physical functioning, and social functioning. As the number of life-events before breast cancer increased, women were at significant risk of experiencing deteriorations overtime in bodily pain, social functioning, role emotional, and vitality. Mediational analyses revealed that perceived stress fully mediated the relationship between initial life-events and two QOL domains; role-emotional and social functioning. Conclusion: Results partially supported the bio-behavioural model of cancer stress, but the model does not appear to fit the data as well as predicted, and may require revision

An empirical framework for studying desistance as a process

Recent reviews of the desistance literature have advocated studying desistance as a process, yet current empirical methods continue to measure desistance as a discrete state. In this paper, we propose a framework for empirical research that recognizes desistance as a developmental process. This approach focuses on changes in the offending rare rather than on offending itself We describe a statistical model to implement this approach and provide an empirical example. We conclude with several suggestions for future research endeavors that arise from our conceptualization of desistance