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Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp ), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans . However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. Here, we show that the overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics, in part, the beneficial effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. PGPH-2 overexpression depletes glycogen stores activating AMP-activate protein kinase, which leads to the HLH-30 nuclear translocation and activation of autophagy, promoting healthy aging. Transcriptomics reveal an HLH-30-dependent longevity and catabolic gene expression signature with PGPH-2 overexpression. Thus, G3PP overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and may be an attractive target for age-related metabolic disorders linked to excess nutrients. Activation of the glycerol shunt mimics calorie restriction, protects from glucotoxicity, and promotes healthy aging. Here, Possik et al. uncover the underlying mechanism and identify the AMPK-TFEB autophagy pathway as critical to the healthy aging phenotype.

Patient engagement in decisions regarding their health care may lead to improved outcomes and improved adherence to treatment plans. While there are several options for involving patients in their health care, goal setting is a readily accessible method for physical therapists to increase the involvement of patients in health care decisions. Physical therapy goals are often generated by health care providers based on subjective information or standardized, fixed-item, patient-reported outcome measures. However, these outcome measures may not fully reveal the activity and participation limitations of individual patients. Goal attainment scaling (GAS) is a patient-centered approach that allows patients to set meaningful goals. While GAS has been shown to be reliable, valid, and sensitive to change in various populations, there is limited evidence in the United States on utilizing GAS in physical therapy for patients with chronic low back pain (LBP). The purpose of this paper is to describe the protocol for a study to (1) develop a way to apply GAS procedures for physical therapists treating patients with chronic LBP in the United States and (2) test the feasibility of applying GAS procedures for chronic LBP in an outpatient physical therapy setting. This study used a mixed methods design with 2 phases: qualitative and quantitative. The qualitative phase of the study employed focus groups of patients with chronic LBP to identify an inventory of goals that were important and measurable. A series of prompts was developed from this inventory to assist physical therapists in collaboratively establishing goals with patients in a clinical setting. The quantitative phase of the study pilot-tested the inventory developed in the qualitative phase in patients with chronic LBP to determine feasibility, reliability, validity, and responsiveness. We also plan to compare how well GAS reveals change over time relative to traditional, fixed-item, patient-reported measures. Phase 1 data collection was completed in June 2020, while data collection for phase 2 was performed between March 2021 and December 2021. We anticipate that this study will demonstrate that GAS can be implemented successfully by outpatient physical therapists, and that it will demonstrate clinically important changes in patients with chronic LBP. GAS represents an opportunity for patient-centered care in the physical therapy management of chronic LBP. While GAS is not new, it has never been studied in real-world physical therapy for chronic LBP in a clinical setting. Due to unique time and productivity constraints, for GAS to be successfully implemented in this environment, we must demonstrate that clinicians can be trained efficiently and reliably, that GAS can be implemented in a clinical setting in under 15 minutes, and that GAS is able to detect clinically meaningful changes in patient outcomes. DERR1-10.2196/32457.