From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing

Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner’s syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner’s syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed

An evaluation of 9-1-1 calls to assess the effectiveness of dispatch-assisted cardiopulmonary resuscitation (CPR) instructions: design and methodology

<p>Abstract</p> <p>Background</p> <p>Cardiac arrest is the leading cause of mortality in Canada, and the overall survival rate for out-of-hospital cardiac arrest rarely exceeds 5%. Bystander cardiopulmonary resuscitation (CPR) has been shown to increase survival for cardiac arrest victims. However, bystander CPR rates remain low in Canada, rarely exceeding 15%, despite various attempts to improve them. Dispatch-assisted CPR instructions have the potential to improve rates of bystander CPR and many Canadian urban communities now offer instructions to callers reporting a victim in cardiac arrest. Dispatch-assisted CPR instructions are recommended by the International Guidelines on Emergency Cardiovascular Care, but their ability to improve cardiac arrest survival remains unclear.</p> <p>Methods/Design</p> <p>The overall goal of this study is to better understand the factors leading to successful dispatch-assisted CPR instructions and to ultimately save the lives of more cardiac arrest patients. The study will utilize a before-after, prospective cohort design to specifically: 1) Determine the ability of 9-1-1 dispatchers to correctly diagnose cardiac arrest; 2) Quantify the frequency and impact of perceived agonal breathing on cardiac arrest diagnosis; 3) Measure the frequency with which dispatch-assisted CPR instructions can be successfully completed; and 4) Measure the impact of dispatch-assisted CPR instructions on bystander CPR and survival rates.</p> <p>The study will be conducted in 19 urban communities in Ontario, Canada. All 9-1-1 calls occurring in the study communities reporting out-of-hospital cardiac arrest in victims 16 years of age or older for which resuscitation was attempted will be eligible. Information will be obtained from 9-1-1 call recordings, paramedic patient care reports, base hospital records, fire medical records and hospital medical records. Victim, caller and system characteristics will be measured in the study communities before the introduction of dispatch-assisted CPR instructions (before group), during the introduction (run-in phase), and following the introduction (after group).</p> <p>Discussion</p> <p>The study will obtain information essential to the development of clinical trials that will test a variety of educational approaches and delivery methods for telephone cardiopulmonary resuscitation instructions. This will be the first study in the world to clearly quantify the impact of dispatch-assisted CPR instructions on survival to hospital discharge for out-of-hospital cardiac arrest victims.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00664443</p