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.
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Optimal maintenance of protein quality is critical for proper cellular functions. Protein turnover (PT) is a critical contributor to protein integrity and serves other functions, such as providing amino acids during starvation or dietary deficiency. By controlling the rates of synthesis and degradation of specific proteins, PT can also help regulate a number of physiological processes, including inflammation, immunity, cholesterol metabolism, and gene transcription. Thus, a decline in PT results not just in the accumulation of damaged and nonfunctional proteins but also has wider implications for overall healthspan and lifespan.
The mechanisms underlying lifespan extension by sulfur amino acid restriction (SAAR) are still unclear. Caloric restriction and SAAR are the two dietary interventions that have shown to extend lifespan in rodent models. A significant number of mechanistic studies suggest that caloric restriction increases PT by increasing autophagy and proteasomal functions. However, some recent studies in C. elegans suggest that lower rates of protein synthesis are associated with lifespan extension. Depending on the biological context, both an increase and a decrease in protein synthesis rates could lead to increased protein quality and contribute to lifespan extension. An increase in protein synthesis would result in less damage under conditions of oxidative stress, but would also cause energy usage. Slower protein synthesis, as a result of SAAR, would lead to a decrease of energy usage. This saved energy could then be used for other cellular functions.
Restriction of protein synthesis not only minimizes cell senescence but also increases the resistance to environmental damage, including UV radiation, oxidative stress, and starvation. These advantages, when coupled with reduced oxidative insult, as shown in previous studies, might lead to a significant improvement in hepatic proteostasis. Additional studies are required to confirm whether slower rates of protein synthesis result in improved proteostasis and whether it is a contributing factor in SAAR-induced lifespan extension.
Aging is a complex, multifactorial process that is driven by the progressive accumulation of several types of cellular damage. Functional impairment at the cellular level causes a multitude of pathologies and disorders in aged individuals. The goal of the aging field is to develop novel therapeutic interventions that extend human health span and reduce the burden of age-related disorders. To explore the molecular determinants that drive cellular aging, as well as how to slow them, researchers have utilized the highly genetically tractable budding yeast S. cerevisiae. Indeed, every intervention known to extend both cellular and organismal health span was identified in yeast, underlining the power of this approach. Importantly, a growing body of work has implicated the process of autophagy as playing a critical role in the delay of aging. This review summarizes recent reports that have identified a role for autophagy or autophagy factors in the extension of yeast lifespan. These studies demonstrate that yeast remains an invaluable tool for the identification and characterization of conserved mechanisms that promote cellular longevity for a number of reasons. Principal among them is the facility with which yeast can be genetically manipulated, as well as the fact that its genome has been well characterized. These features, combined with ease of growth and a short doubling time, conspire to make yeast highly amenable to a variety of high-throughput screening procedures. The use of yeast as an experimental system also allows for incomparably rapid lifespan experiments. Perhaps most importantly, since many of the pathways regulating longevity are conserved from yeast to more complex eukaryotes, including mammals, novel pharmaceutical or nutritional regulators of these processes that are identified in yeast will likely be translatable to the ultimate goal of delaying aging and improving the health span of humans. These studies also demonstrate that the process of autophagy has been implicated in nearly all known longevity-promoting manipulations and thus represent an ideal target for interventions aimed at improving human health span.