ORALLY ADMINISTERED UROLITHIN A IS SAFE AND MODULATES MUSCLE AND MITOCHONDRIAL BIOMARKERS IN ELDERLY

Abstract

Aging causes a gradual decline in normal physiological functions and represents a significant risk factor for several key diseases. Key environmental factors, including diet, play an important role along with genetic factors in determining lifespan. The sirtuins are a family of histone deacetylases that target histone and non-histone proteins for removal of acetyl groups from lysine residues. A gain of function of Sir2 (S. Cerevisiae), or its orthologs in other species, is associated with increased lifespan and healthspan. We asked whether the enzyme controlling the opposite reaction, the histone acetyltransferase p300/CBP might also influence lifespan. We indeed observed that a p300/CBP inhibitor and/or loss of p300/CBP function changes specific acetylation patterns and influence lifespan, muscle function, stress response and reproductive fitness in aged C. elegans. These findings highlight the potential regulatory role of p300/CBP on the aging process. Advanced dementia is a terminal condition. Foregoing burdensome interventions such as artificial nutrition or admission to hospital at the end of life is part of high-quality palliative care. In advanced, decisions regarding such interventions are made by health care proxies (HCPs). Different attitudes in HPCs and nurses regarding burdensome interventions might influence decision making and thus indirectly the resident's wellbeing. We therefore investigated if HPC and nurses differ in their attitudes towards burdensome medical interventions in nursing home residents with advanced demen-tia. The Zurich Life and Death with Advanced Dementia (ZULIDAD) study addresses the last phase of life of nursing home residents in Switzerland by asking HCPs (N = 126) and primary nurses (N = 99) quarterly with comprehensive questionnaires about the resident's health, quality of life and current treatment during three years. At baseline, HCPs and nurses were asked whether antibiotics, artificial administration of fluids, artificial nutrition, artificial respiration , cardiopulmonary resuscitation and admissions to hospital should be foregone even though this can potentially shorten the resident's life expectancy. Overall, HCPs and nurses were found to favor foregoing burdensome interventions in residents with advanced dementia. However, a minority of participants supports their implementation. Interestingly, nurses were found to be significantly "less palliative" in their attitudes than HCPs except for the sub-cutaneous administration of fluids. Further research needs to elucidate why a minority of HCPs and nurses favor a more aggressive treatment approach and how this impacts decision making at the end of life in dementia. Misinformation and lack of understanding of memory loss, dementia and brain health are barriers to dementia risk reduction and timely health seeking behaviour. Online video technology for health promotion has been popularised with the increase in online networks, improved access to technology , and the rise of online health seeking behaviour. However, an understanding of the efficacy of this technology in the context of brain health awareness in older adults is lacking. This research explored whether three short animated brain health videos could reduce worry, impart new knowledge, and promote behavioural change in older adults.Participants (8,179) completed a survey pre-and post-engagement with three animated films that we had developed. Participants' level of worry significantly decreased, and over half of the participants indicated that they intended to change their behaviour after watching the videos. The majority of participants indicated they had learned something new from the videos, and found the videos enjoyable. Regression analysis described how participants who reported learning from the videos were more likely to report behavioural change. In addition, enjoyment significantly predicated outcomes of learning and behaviour change. This research contributes a novel understanding of the use of online video technology to change perceptions of brain health in older adults. Vitamin D has multiple roles including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvi-taminD, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases including Alzheimer's disease, Parkinson's disease, cognitive impairment , and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that Vitamin D3-induced lifespan extension requires the stress response pathway genes SKN-1, IRE-1, and XBP-1. Vitamin D3 (D3) induced expression of SKN-1 target genes, but not canonical targets of IRE-1/ XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels, and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.