This year, OFAS hosted a pre-meeting session at the AGE 47th Annual Meeting in Philadelphia. The theme of the conference was “Improving Resiliency to Delay Aging”, and the OFAS-sponsored session was focused on Nutrition and Longevity. The panel of speakers included: Dr. Sebastian Brandhorst from University of Southern California; Dr. John Newman from the Buck Institute and UCSF; Dr. John P. Richie from Penn State University; and Dr. Brian Kennedy from the Yong Loo Lin School of Medicine at the National University of Singapore. There were 261 attendees present at the meeting, including some directors for the Nathan Shock Centers and NIH-NIA.
For years, Orentreich Foundation for the Advancement of Science has researched biomedical interventions to prevent, halt, or reverse those disorders that decrease the quality or length of life. Our groundbreaking research on dietary methionine restriction has shown its dramatic ability to increase longevity while improving healthspan, lowering body weight, and reducing the incidence of age-related diseases.
In addition to our dedication to discovery, we are also committed to promoting the exchange of knowledge and strengthening of relationships within the scientific community. We host a biennial symposium on healthy aging, support meetings in the field, and, each year, our scientists represent us at conferences and seminars around the globe.
In our minds, old age is often associated with negative outcomes, such as a decline in physical health, but research consistently finds that older adults tend to experience more positive emotion than their younger counterparts. In this study, older adults reported greater awareness of being in the present moment, also known as mindfulness, than younger adults. Furthermore, this mindfulness helped to explain why older adults reported more positive emotion than younger adults do, suggesting that mindfulness facilitates healthy aging.
The researchers asked participants about their mood, mindfulness, and perspective on the future to see how these factors might be related. The participants reported their current positive and negative emotions, such as enthusiasm, fear, interest, and hostility. They reflected on how much they were mindfully aware in the moment, rather than living in the past or anticipating the future. And participants considered whether they felt concerned about the limited time left in their life or positive about the opportunities awaiting them.
The older adults tended to recognize that they had fewer remaining years on earth than the younger participants, but they also felt greater positive emotion. And according to the researchers’ analysis, it was their focus on the here and now—their greater mindfulness compared to young people—that explained their good moods. The higher their mindfulness, the better they felt. Since being mindful could help us regulate our emotions and relieve stress, it could be useful for humans to naturally grow in mindfulness as we get older. This is significant because positive emotions can also lead to better physical health. However, implications of these findings for health and well-being in younger and older adults are still being discussed.
The hallmarks of aging in skeletal muscle include endothelial cell dysfunction, impaired microcapillary formation, and a progressive decline in exercise capacity, yet the underlying causes of these symptoms are poorly understood. In a recent paper, researchers identify the mechanism behind vascular aging in mice and its effects on muscle health, and show the means by which they successfully reversed the process in animals.
The vascular aging process causes us to suffer from disorders such as cardiac and neurologic conditions, muscle loss, impaired wound healing, and overall frailty. As we age, our tiniest blood vessels wither and die, causing reduced blood flow and compromised oxygenation of organs and tissues. Endothelial cells are essential for the health and growth of the blood vessels that they line. Unfortunately, as these endothelial cells age, blood vessels deteriorate, new blood vessels fail to form, and blood flow to most parts of the body gradually diminishes. This process heavily affects the muscles, which are vascularized and rely on a robust blood supply to function. Exercise can slow the process, but over time, it becomes less effective.
The research team found that reduced blood flow develops as endothelial cells start to lose a critical protein known as SIRT1, which has been known to delay aging and extend life in yeast and mice. SIRT1 loss is precipitated by the loss of NAD, a key regulator of protein interactions and DNA repair. Through a series of experiments, researchers found that NAD+ and SIRT1 provide a signaling network between endothelial cells in the walls of blood vessels and muscle cells, thus generating new capillaries to supply oxygen and nutrients to tissues and organs. By using an NAD+ precursor treatment in aging mice, the scientists saw a boost in the number of blood capillaries and capillary density, increasing the blood flow to muscles. These findings have implications for improving blood flow, increasing human performance, and reestablishing a cycle of mobility in the elderly, paving the way for therapies to address diseases that arise from vascular aging.
Over the past ten years, understanding of the physiological changes that occur as people age has greatly improved. Common mechanisms seem to support several age-related diseases, including diabetes, Parkinson’s disease and Alzheimer’s. A review of more than 400 studies of people and animal models indicates that similar processes are the basis of DNA damage, cellular senescence, or inflammation and autophagy. Over the years, studies have shown that one age-related disease can accelerate the onset of others. Until now, aging research has focused mainly on single diseases or on delaying death, meaning that the fundamental mechanisms of aging are being missed as targets for the treatment or prevention of several age-related conditions. What’s more, patients multiple diseases are being exposed to many drugs at once, often with adverse effects.
A class of drugs called geroprotectors might be able to delay the onset of concurrent age-related diseases (multimorbidity) and boost resilience. In various animal models, these drugs can ward off problems of the heart, muscles, immune system and more. However, there are various factors, such as agreeance on definitions and desired metrics, preventing these drugs from reaching the clinic. With an ever-increasing aging population and the social and health-care systems of many nations close to a crisis point, we must take a different approach. Proof-of-concept clinical studies could demonstrate the value of geroprotectors as boosters of resilience in frail patients within the next decade. If successful, such studies could catalyze efforts to advance definitions, animal models, and the characterization of measurable outcomes against which to test the drugs.
To read the full article, click here.
The ultimate goal of aging research is to develop therapeutic means to extend human lifespan, while reducing susceptibility to many age-related diseases including cancer, as well as metabolic, cardiovascular and neurodegenerative disorders. However, this first requires clarification of the causes of aging, which has been greatly facilitated by the use of model organisms. In particular, the budding yeast Saccharomyces cerevisiae has been vital in the identification of conserved molecular and cellular determinants of aging and for the development of approaches to manipulate these aging determinants to extend lifespan. Past studies have shown that all means to experimentally extend lifespan result in the initiation of cellular stress responses which, in turn, increases the process of autophagy.
This review describes growing evidence in yeast that activation of the integrated stress response contributes significantly to lifespan extension. Thus, therapeutics to directly activate autophagy could be another promising approach to extend lifespan and healthspan. There are many different types of autophagy, and in order to have a better understanding of the aging process, it is crucial to know the specific autophagy pathways that need to be activated in order to extend yeast lifespan. This could then lead to the discovery of pharmaceutical and physiological regulators of these processes in yeast, which will likely have biological significance to human health and aging. It should also be noted that the impressive pace of research and discoveries being made using the yeast model organism indicate that it will continue to be a central model for aging studies in the near future.
You can find the full paper here.