Thomas Gustafsson

The increasing number of older people being disabled by aging threatens the sustainability of the health systems. Thus, there is an urgent need to counteract aging-induced disabling conditions as muscle wasting. The proposed project is based on longitudinal observations across the lifespan of adults in a cohort born in 1956/58 (SPAF-1958). This cohort has been followed from age 16 to 63 years using objective measures of physical performance, physical activity, and lifestyle variables at four time points, available and skeletal muscle biopsies (at 27 and 63 years) and blood samples (at ages 52 and 63 years). The SPAF-1958 cohort provides a unique opportunity to detect longitudinal changes, i.e., individual trajectories, thus elucidating the preclinical and clinical course of sarcopenia and revealing underlying factors at the individual level. In the proposed study, measurements will be repeated at age 67 years since it is reasonable to shorten the intervals between follow-ups as the effects of aging increase with time. A unique feature of the current study as individuals enter early-aging, is the combination of analyses of neurogenic components. This includes examination of motor and sensory nerve conduction, number of motor units combined with measurements of muscle mass and quality by MRI and muscle tissue morphology and gene expression from biopsies. The current study may also add information about biological aging biomarkers in blood and individual genetic makeup.

Critical limb threatening ischemia (CLTI) is a significant unresolved health issue for a growing percent of the population. In this disease, arterial blockage reduces blood flow to the muscles of the lower leg, which is referred to as ischemia. Individuals with CLTI suffer a range of negative outcomes, including limb amputation and death. Clinical treatments to restore blood flow to the limb can delay the need for limb amputation but have had limited success in improving patient health. Particularly, the ischemic muscle remains damaged, which results not just in limited mobility but also lowers overall health. We will examine a specific type of cell within blood vessels, called a pericyte, and whether it contributes to the problems seen in the ischemic muscle. We will conduct analyses of patient sample and use a combination of animal models and cultured cell experiments. By tracking the transition in what happens to these pericytes during ischemia, and through examining what triggers them to behave in deleterious ways, we will identify potential new ways to improve the health of CLI patients.

Critical limb threatening ischemia (CLTI) is a significant unresolved health issue for a growing percent of the population. In this disease, arterial blockage reduces blood flow to the muscles of the lower leg, which is referred to as ischemia. Individuals with CLTI suffer a range of negative outcomes, including limb amputation and death. Clinical treatments to restore blood flow to the limb can delay the need for limb amputation but have had limited success in improving patient health. Particularly, the ischemic muscle remains damaged, which results not just in limited mobility but also lowers overall health. We will examine a specific type of cell within blood vessels, called a pericyte, and whether it contributes to the problems seen in the ischemic muscle. We will conduct analyses of patient sample and use a combination of animal models and cultured cell experiments. By tracking the transition in what happens to these pericytes during ischemia, and through examining what triggers them to behave in deleterious ways, we will identify potential new ways to improve the health of CLI patients.