A cross-sectional study of ageing at the mouse neuromuscular junction and effects of an experimental therapeutic approach for dynapenia.

Despite prior efforts to understand and target dynapenia (age-induced loss of muscle strength), this condition remains a major challenge that reduces the quality of life in the aged population. We have focused on the neuromuscular junction (NMJ) where changes in structure and function have rarely been systematically studied as a dynamic and progressive process. Our cross-sectional study found neurotransmission at the male mouse NMJ to be biphasic, displaying an early increase followed by a later decrease, and this phenotype was associated with structural changes to the NMJ. A cross-sectional characterization showed that age-induced alterations fell into four age groups: young adult (3-6 months), adult (7-18 months), early aged (19-24 months), and later aged (25-30 months). We then utilized a small molecule therapeutic candidate, GV-58, applied acutely during the later aged stage to combat age-induced reductions in transmitter release by increasing calcium influx during an action potential, which resulted in a significant increase in transmitter release. This comprehensive study of neuromuscular ageing at the NMJ will enable future research to target critical time points for therapeutic intervention. KEY POINTS: Age-induced frailty and falls are the leading causes of injury-related death and are caused by an age-induced loss of muscle strength due to a combination of neurological and muscular changes. A cross-sectional approach was used to study age-induced changes to the neuromuscular junction in a mouse model, and physiological changes that were biphasic over the ageing time course were found. Changes in physiology at the neuromuscular junction were correlated with alterations in neuromuscular junction morphology. An acutely applied positive allosteric gating modifier of presynaptic voltage-gated calcium channels was tested as a candidate therapeutic strategy that could increase transmitter release at aged neuromuscular junctions. These results provide a detailed time course of age-induced changes at the neuromuscular junction in a mouse model and test a candidate therapeutic strategy for weakness.

Prevalence of malnutrition in general surgical patients.

The possibility of protein-calorie malnutrition (PCM) was studied on one hundred consecutive patients admitted to the department of surgery at the Saint Georges Hospital, Beirut, during the months of April and June 1991, regardless of age, sex and socio-economic status. Data was completed on 94 of those cases. Multiple parameters were studied, including measurements of triceps and subscapular skinfold thickness, mid-arm muscle circumference, percent weight loss, creatinine height index, serum albumin and transferrin levels and total lymphocyte count. We found a prevalence of 81%, 65%, 53% and 31% of PCM, if one, two, three or at least four abnormal parameters are used respectively, to assess malnutrition. Defining malnutrition as the presence of at least three abnormal parameters, we conclude that 53% of the patients, on admission to the department of surgery, had evidence of PCM. Further studies are required to assess the impact of this prevalence on length of stay, morbidity and mortality.