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Department of Biological and Medical Sciences
Faculty of Health and Life Sciences
The number of people aged over 65 is expected to double in the next 30 years. For many, living longer will mean spending more years with the burdens of chronic diseases such as Alzheimer’s, cardiovascular disease, and diabetes. Although researchers have made rapid progress in developing geroprotective interventions that target mechanisms of ageing and delay or prevent the onset of multiple concurrent age-related diseases, a lack of standardized techniques to assess healthspan in preclinical murine studies has resulted in reduced reproducibility and slowed progress. To overcome this, major centres in Europe and the USA skilled in healthspan analysis came together to agree upon a toolbox of techniques which can be used to consistently assess the healthspan of mice. Here, we describe the agreed toolbox which contains protocols for echocardiography, novel object recognition, grip strength, rotarod, glucose and insulin tolerance tests, body composition, and energy expenditure. They can be performed longitudinally in the same mouse over a period of 4-6 weeks to test how candidate geroprotectors affect cardiac, cognitive, neuromuscular and metabolic health.
The proportion of the population over the age of 65 is growing the most rapidly due to the longevity revolution. Frailty is prevalent in this age group and strongly associated with disability and hospitalization, having a significant impact on the costs of health and social care. New effective interventions to delay or reverse frailty are urgently required. Geroprotectors are a new class of drugs, which target fundamental mechanisms of ageing and show promise in delaying the onset of or boosting resilience in frail older people. However, there are challenges to their clinical translation. Here we review the literature for evidence that frailty can be delayed or reversed and geroprotectors can improve frailty in murine models and in patients. We will then discuss the challenges, which make their clinical testing complex and propose potential options for moving forward.
One of the major challenges currently facing healthcare providers is an ageing population that is spending more time in ill-health. Many ageing individuals have multiple and complex needs which affect the ability to treat them effectively, which also has a significant impact on their own independence and quality of life. There are many aspects of testing interventions to improve health in old age in pre-clinical models; from breeding strategies to measurements of outcomes. Here we provide a brief overview of the major considerations to take into account in such studies and the limitations or challenges we face in these studies.
A great majority of genes present in the human genome are also present in the mouse, thus making it an attractive mammalian model organism to study gene function and dysfunction. Over the past few decades, the ability to manipulate the mouse genome has been developed in a variety of ways. A complementary methodology to create mutations in the mouse is to use chemical mutagenesis. N‐ethyl‐N‐Nitrosourea (ENU) is the mutagen of choice for creating random point mutations model organisms. Advances in sequencing technologies have resulted in a rapid identification of the causative mutation. ENU mutagenesis is a powerful hypothesis‐generating approach to create new mouse models through both forward and reverse genetics approaches. Furthermore, the addition of challenges can identify mutations affecting specific pathways, and specific mutant lines or strains can be used to identify modifiers.
An increased lifespan comes with an associated increase in disease incidence, and is the major risk factor for age-related diseases. To face this societal challenge search for new treatments has intensified requiring good preclinical models, whose complexity and accuracy is increasing. However, the influence of ageing is often overlooked. Furthermore, phenotypic assessment of ageing models is in need of standardisation to enable the accurate evaluation of pre-clinical intervention studies in line with clinical translation.
This article gives an overview about the aging in rodents and how rodents can be used for aging modelling. The article starts with more general consideration about the modelling and some basic background. It is followed by the review of the most common progeroid syndromes along with the molecular mechanisms of aging. Then the effect of caloric restriction is described in deeper details. And finally, the role of transposable elements and the role of their activation during aging is described. Therefore, present article covers broadly the modelling of aging in the rodents with some more detailed overviews for the mechanisms explaining the potential interventions to modify the aging and aging related problems.