Key pointsr The endogenous molecular clock in skeletal muscle is necessary for maintenance of phenotype and function.r Loss of Bmal1 solely from adult skeletal muscle (iMSBmal1 −/− ) results in reductions in specific tension, increased oxidative fibre type and increased muscle fibrosis with no change in feeding or activity.r Disruption of the molecular clock in adult skeletal muscle is sufficient to induce changes in skeletal muscle similar to those seen in the Bmal1 knockout mouse (Bmal1 −/− ), a model of advanced ageing. r This study uncovers a fundamental role for the skeletal muscle clock in musculoskeletal homeostasis with potential implications for ageing.Abstract Disruption of circadian rhythms in humans and rodents has implicated a fundamental role for circadian rhythms in ageing and the development of many chronic diseases including diabetes, cardiovascular disease, depression and cancer. The molecular clock mechanism underlies circadian rhythms and is defined by a transcription-translation feedback loop with Bmal1 encoding a core molecular clock transcription factor. Germline Bmal1 knockout (Bmal1 KO) mice have a shortened lifespan, show features of advanced ageing and exhibit significant weakness with decreased maximum specific tension at the whole muscle and single fibre levels. We tested the role of the molecular clock in adult skeletal muscle by generating mice that allow for the inducible skeletal muscle-specific deletion of Bmal1 (iMSBmal1). Here we show that disruption of the molecular clock, specifically in adult skeletal muscle, is associated with a muscle phenotype including reductions in specific tension, increased oxidative fibre type, and increased muscle fibrosis similar to that seen in the Bmal1 KO mouse. Remarkably, the phenotype observed in the iMSBmal1 −/− mice was not limited to changes in muscle. Similar to the germline Bmal1 KO mice, we observed significant bone and cartilage changes throughout the body suggesting a role for the skeletal muscle molecular clock in both the skeletal muscle niche and the systemic milieu. This emerging area of circadian rhythms and the molecular clock in skeletal muscle holds the potential to provide significant insight into intrinsic mechanisms of the maintenance of muscle quality and function as well as identifying a novel crosstalk between skeletal muscle, cartilage and bone.

In 1976, in a small, remote Libyan village, one apparently sick camel was slaughtered and skinned, and the camel meat was distributed for human comsumption. A few days later, 15 villagers suffered a severe febrile illness. Of the five individuals who had participated in the killing and dispensation of the camel, all were dead within four days. When samples of serum from nine of the remaining patients were examined, seven were found to be positive for plague as determined by the passive hemagglutination test. Another six persons became ill after killing two goats, and the serum of one goat contained antibodies to Yersinia pestis. Because all of the remaining patients except one were treated early enough, they recovered. These incidents confirm previous reports that the camel and the goat are susceptible to naturally occurring plague infection and have a significant role in the dissemination of human plague.

The study of Graylingwell Hospital conducted by Roth (1955) has in part been replicated in order to study the changing patterns of mental illness in the elderly over a 25-year period. Important changes in the diagnostic distribution and outcome of cases admitted have occurred. Functional illness has given way to dementia, not as a proportion of patients admitted but in the number of beds employed for their care 6 and 24 months after their index admission. Discharge rates for all diagnostic groups except acute confusional states, have undergone considerable change and death rates have fallen. The study has concentrated on the residual in-patient population, paying particular attention to increasing demand for beds for the dementing group. These changes have been quantified and reflect a four-year increase in bed requirements for cases of dementia at two years. Despite a striking reduction in requirement for functional cases, there is an overall increase in bed requirement of 38 per cent at the two-year mark.

Two groups of patients suffering from Senile Dementia of the Alzheimer Type (S.D.A.T.) have been studied from first referral till death in hospital. The point o f separation between the two groups was agethe younger group were aged 65-74 at t h e time of terminal admission and the older over 85.The variables studied were history of illness prior to referral. assessment on the Crichton Royal Behavioural Rating Scale at the time of terminal admission, duration of illness and duration of hospital stay. The last two factors were measured both in absolute terms and as features relative to life expectancy.The history proved unhelpful in identifying features capable of separating the two groups. Although in absolute terms the younger group survived longer. both from onset of illness and admission. in relative terms these patients fared considerably worse.The possibility that S.D.A.T. in the very elderly runs a more benign course is discussed.

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