The integrated stress response in budding yeast lifespan extension

The integrated stress response in budding yeast lifespan extension

mic-04-368-g01The 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.

High Fat Diet Improves Healthspan and Memory

High Fat Diet Improves Healthspan and Memory

kd memory graphA recent study has demonstrated that a ketogenic diet significantly improved memory in aging mice and increased the animal’s chances of surviving to old age, opening up a new area of inquiry in aging research.

Eating a ketogenic diet – which is high in fat and low in protein and carbohydrates – ramps up the number of ketone bodies. In this study, Newman et al. carefully designed three diets that were matched in every way except fat and carbohydrate content: a normal high-carbohydrate diet, a zero-carbohydrate ketogenic diet, and a high-fat, low-carbohydrate diet that was not ketogenic. Mice were fed the ketogenic diet intermittently to prevent them from becoming obese, starting at one year old, which is middle age for mice.

The ketogenic diet-fed mice had a lower risk of dying as they aged from one to two years old, although their maximum lifespan was unchanged. Another group of mice underwent memory testing at both middle age (one year old) and old age (two years old). Mice that had been eating a ketogenic diet performed at least as well on memory tests at old age as they did at middle age, while mice eating the normal diet showed an expected age-associated decline. Mice who ate the ketogenic diet also explored more, and their improved memory was confirmed with another test a few months later.

According to the paper, gene expression could explain the cognitive improvement. Future work to understand the nature of the persistent effect on memory in particular may lead to therapies to promote cognitive resilience to dementia or illness-associated delirium.

High Fat Diet Extends Longevity and Healthspan

High Fat Diet Extends Longevity and Healthspan

KD longevity graph

As more people age well past their 70s, researchers have increasingly explored the issues of health and quality of life during aging. A recent mouse study at the UC Davis School of Veterinary Medicine sheds revealed that a high-fat, or ketogenic, diet not only increases longevity, but improves physical strength as well.

Ketogenic diets have gained popularity for a variety of health benefit claims, but scientists are still teasing out what happens during ketosis, when carbohydrate intake is so low that the body shifts from using glucose as the main fuel source to burning fat and producing ketones for energy.

While calorie restriction has been shown to slow aging in many animals, Roberts et. al. were interested in how a high-fat diet may impact the aging process. In their research, they found  a 13% increase in median life span for the mice on a high-fat versus high-carb diet.

The study mice were split into three groups: a regular rodent high-carb diet, a low-carb/high-fat diet, and a ketogenic diet (89-90 percent of total calorie intake). Originally concerned that the high-fat diet would increase weight and decrease lifespan, the researchers kept the calorie count of each diet the same.

In addition to significantly increasing the median lifespan of mice in the study, the ketogenic diet increased memory and motor function, prevented an increase in age-related markers of inflammation, and reduced the incidence of tumors. This indicates that a ketogenic diet can have a major impact on life- and health span without major weight loss or restriction of food intake. It also opens a new avenue for possible dietary interventions that have an impact on aging.

Future studies are warranted to investigate the mechanisms through which this diet works and to optimize diet composition and feeding approaches to further extend healthspan.

Preliminary Findings on the Effects of Rapamycin on Cardiac Health of Companion Dogs

Preliminary Findings on the Effects of Rapamycin on Cardiac Health of Companion Dogs

Recent advances in geroscience have begun to explain the molecular mechanisms that link aging with disease, making age the greatest risk factor for most causes of mortality. Potential therapeutic strategies to delay age-related disability and disease and increase healthy lifespan have emerged. Among these is rapamycin, a drug intervention that has been shown to increase lifespan and healthspan in rodent models.

Companion animals are subject to similar risk factors, receive comparable medical care, and develop many of the same age-related diseases humans do. Dr. Matt Kaeberlein, of the Dog Aging Project, conducted a study of a small group of healthy middle-aged dogs receiving either a dose of rapamycin or a placebo. Dogs age similarly to humans, but their lives are much shorter and they age more quickly; therefore aging studies on dogs can yield answers in as little as three to five years, as opposed to human clinical trials that can take decades.  The results yielded no clinical side effects and an echocardiography seemed to show improvement in cardiac function. Based on these findings, another, longer study will be done with a larger group of dogs in order to confirm the effects on heart function and behavior. It will also help to determine whether there are differences in mortality and prevalence of age-related diseases.

Dr. Kaeberlein’s work in translational geroscience seeks to close the gap between promising lab findings and possible applications for humans and to improve the quality of life for pets and their owners. You can read his most recent paper here or you can watch his presentation from the joint OFAS-New York Academy of Sciences conference Aging and Nutrition: Novel Approaches and Techniques.

 

NYAS eBriefing now available for Aging and Nutrition: Novel Approaches and Techniques

NYAS eBriefing now available for Aging and Nutrition: Novel Approaches and Techniques

The New York Academy of Sciences recently announced that the multimedia eBriefing of the symposium, Aging and Nutrition: Novel Approaches and Techniques, is now available.

On December 2, the Orentreich Foundation for the Advancement of Science and the Sackler Institute for Nutrition Science at the New York Academy of Sciences convened the conference Aging and Nutrition: Novel Approaches and Techniques. Leading researchers in the field gathered to discuss the use of established and emerging interventions in nutrition and metabolism to extend lifespan and impact healthy aging.

Academy eBriefings help you stay informed about the new research discussed at NYAS conferences and symposia. Click the link to read highlights of the talks or drill deeper and watch a selection of the speakers’ presentations.