Yeo, Dongwook

Abstract Brief inhalation of carbon dioxide (CO 2 ) has been proposed to counteract transient hypocapnia by enhancing oxygen unloading, vasodilation, and sympathetic modulation. Despite these potential ergogenic mechanisms, CO 2 has rarely been investigated in the exercise context. The present study investigated whether brief CO 2 inhalation (iCO 2 ) influences performance and recovery during high‐intensity interval exercise. Nine healthy adults completed two randomized, single‐blinded crossover trials of repeated cycling intervals at 85% peak work rate until volitional exhaustion or cadence dropped below 60 rpm, with a minimum 2‐min interval duration required and 3‐min active recovery between bouts. Participants inhaled 5% CO 2 or room air (15 breaths) before and after each exercise bout. Gas exchange, cardiovascular responses, and perceived exertion were assessed. Total exercise time was similar between trials; however, participants completed more intervals with iCO 2 . During the first interval, iCO 2 increased exercise duration and VO 2 . At matched exercise time, perceived exertion and dyspnea were lower with iCO 2 . During recovery, systolic blood pressure was lower and heart rate was higher following iCO 2 . Brief iCO 2 improved first‐interval performance, altered cardiovascular recovery, and reduced perceptual strain but did not extend overall exercise duration. These findings suggest iCO 2 may transiently modulate tolerance and autonomic‐vascular responses during high‐intensity interval exercise.

Abstract Histone deacetylase 3 (Hdac3) is an epigenetic regulator of gene expression and interacts with skeletal transcription factors such as Runx2. We previously reported that conditional deletion of Hdac3 in Osterix-Cre recombinase-expressing osteoprogenitor cells (Hdac3 CKOOsx) caused osteopenia and increased marrow adiposity, both hallmarks of skeletal aging. We also showed that Runx2+ cells within osteogenic cultures of Hdac3-depleted bone marrow stromal cells (BMSCs) contain lipid droplets (LDs). Cellular senescence, a nonproliferative metabolically active state, is associated with increased marrow adiposity, bone loss, and aging. In this study, we sought to determine if Hdac3 depleted Runx2+ pre-osteoblasts from young mice exhibit chromatin changes associated with early cellular senescence and how these events correlate with the appearance of LDs. We first confirmed that BMSCs from Hdac3 CKOOsx mice have more Runx2 + LD+ cells compared with controls under osteogenic conditions. We then measured senescence-associated distention of satellite (SADS) DNA and telomere-associated foci (TAFs) in Hdac3 CKOOsx and control BMSCs. In situ, Runx2+ cells contained more SADS per nuclei in Hdac3 CKOOsx femora than in controls. Runx2+ BMSCs from Hdac3 CKOOsx mice also contained more SADS and TAFs per nuclei than Runx2+ cells from age-matched control mice in vitro. SADs and TAFs were present at similar levels in Runx2 + LD+ cells and Runx2 + LD− cells from Hdac3 CKOOsx mice. Hdac inhibitors also increased the number of SADS in Runx2 + LD+ and Runx2 + LD− WT BMSCs. Senolytics reduced viable cell numbers in Hdac3 CKOOsx BMSC cultures. These data demonstrate that the depletion of Hdac3 in osteochondral progenitor cells triggers LD formation and early events in cellular senescence in Runx2+ BMSCs through mutually exclusive mechanisms.

Nicotinamide adenine dinucleotide (NAD) is a versatile chemical compound serving as a coenzyme in metabolic pathways and as a substrate to support the enzymatic functions of sirtuins (SIRTs), poly (ADP-ribose) polymerase-1 (PARP-1), and cyclic ADP ribose hydrolase (CD38). Under normal physiological conditions, NAD+ consumption is matched by its synthesis primarily via the salvage pathway catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). However, aging and muscular contraction enhance NAD+ utilization, whereas NAD+ replenishment is limited by cellular sources of NAD+ precursors and/or enzyme expression. This paper will briefly review NAD+ metabolic functions, its roles in regulating cell signaling, mechanisms of its degradation and biosynthesis, and major challenges to maintaining its cellular level in skeletal muscle. The effects of aging, physical exercise, and dietary supplementation on NAD+ homeostasis will be highlighted based on recent literature.