No abstract

This prospective, two-site, randomized, controlled pilot study assessed the feasibility of an enhanced physical activity (EPA) intervention in hospitalized children and adolescents receiving treatment for a solid tumor or for acute myeloid leukemia (AML), and assessed different statistical techniques to detect the intervention's sleep and fatigue outcomes. Twenty-nine patients (25 with a solid tumor and 4 with AML) participated. Data were collected from actigraph; patient, parent, and staff nurse reports of patient fatigue; parent sleep diaries; and patient charts. The intervention was successfully implemented 85.4% of the scheduled times. We used two different statistical methods to analyze the longitudinal data. Using an ANOVA model, sleep was significantly more efficient in the experimental arm than in the control arm when daily differences from baseline sleep efficiency values were averaged and compared (F=4.17, P=0.053). However, in a mixed model (repeated measures) analysis, sleep duration (F=0.54, P=0.47) and sleep efficiency (F=0.04, P=0.85) were not seen to differ between study arms. We conclude that an inpatient intervention of EPA can be delivered to children and adolescents receiving chemotherapy. Our findings identify design and statistical considerations for a future effectiveness study of the EPA intervention in hospitalized pediatric oncology patients.

No abstract

Cellular senescence is a well-orchestrated programmed process involved in age-related pathologies, tumor suppression and embryonic development. TGF-β/Smad is one of the predominant pathways that regulate damage-induced and developmentally programmed senescence. Here we show that canonical TGF-β signaling promotes senescence via miR-29-induced loss of H4K20me3. Mechanistically, oxidative stress triggers TGF-β signaling. Activated TGF-β signaling gives rise to acute accumulation of miR-29a and miR-29c, both of which directly suppress their novel target, Suv4-20h, thus reducing H4K20me3 abundance in a Smad-dependent manner, which compromises DNA damage repair and genome maintenance. Loss of H4K20me3 mediated by the senescent TGF-β/miR-29 pathway contributes to cardiac aging in vivo. Disruption of TGF-β signaling restores H4K20me3 and improves cardiac function in aged mice. Our study highlights the sequential mechanisms underlying the regulation of senescence, from senescence-inducing triggers to activation of responsive signaling followed by specific epigenetic alterations, shedding light on potential therapeutic interventions in cardiac aging.