Selenium supplementation protects against obesity and may extend lifespan

Adding the nutrient selenium to diets protects against obesity and provides metabolic benefits to mice, according to a study published today in eLife.

The results could lead to interventions that reproduce many of the anti-aging effects associated with dietary restriction while also allowing people to eat as normal.

Several types of diet have been shown to increase healthspan – that is, the period of healthy lifespan. One of the proven methods of increasing healthspan in many organisms, including non-human mammals, is to restrict dietary intake of an amino acid called methionine.

Recent studies have suggested that the effects of methionine restriction on healthspan are likely to be conserved in humans. Although it might be feasible for some people to practice methionine restriction, for example, by adhering to a vegan diet, such a diet might not be practical or desirable for everyone. In the current study, a research team from the Orentreich Foundation for the Advancement of Science (OFAS), Cold Spring, New York, US, aimed to develop an intervention that produces the same effects as methionine restriction, while also allowing an individual to eat a normal, unrestricted diet.

An important clue for developing such a treatment is that methionine restriction causes a decrease in the amounts of an energy-regulating hormone called IGF-1. If a treatment could be found that causes a similar decrease in IGF-1, this might also have beneficial effects on healthspan. Previous research has shown that selenium supplementation reduces the levels of circulating IGF-1 in rats, suggesting that this could be an ideal candidate.

The team first studied whether selenium supplementation offered the same protection against obesity as methionine restriction. They fed young male and older female mice one of three high-fat diets: a control diet containing typical amounts of methionine, a methionine-restricted diet, and a diet containing typical amounts of methionine as well as a source of selenium. For both male and female mice of any age, the authors found that selenium supplementation completely protected against the dramatic weight gain and fat accumulation seen in mice fed the control diet, and to the same extent as restricting methionine.

Next, they explored the effects of the three diets on physiological changes normally associated with methionine restriction. To do this, they measured the amounts of four metabolic markers in blood samples from the previously treated mice. As hoped, they found dramatically reduced levels of IGF-1 in both male and female mice. They also saw reductions in the levels of the hormone leptin, which controls food intake and energy expenditure. Their results indicate that selenium supplementation produces most, if not all, of the hallmarks of methionine restriction, which suggests that this intervention may have a similar positive effect on healthspan.

To gain insight into the beneficial effects of selenium supplementation, the researchers used a different organism – yeast. The two most widely used measurements of healthspan in yeast are chronological lifespan, which tells us how long dormant yeast remain viable, and replicative lifespan, which measures the number of times a yeast cell can produce new offspring. The team previously showed that methionine restriction increases the chronological lifespan of yeast, so they tested whether selenium supplementation might do the same. As it turned out, yeast grown under selenium-supplemented conditions had a 62% longer chronological lifespan (from 13 days to 21 days) and a replicative lifespan extended by nine generations as compared with controls. This demonstrates that supplementing yeast with selenium produces benefits to healthspan detectable by multiple tests of cell aging.

“One of the major goals of aging research is to identify simple interventions that promote human healthspan,” notes senior author Jay Johnson, Senior Scientist at OFAS. “Here we present evidence that short-term administration of either organic or inorganic sources of selenium provides multiple health benefits to mice, the most notable of which being the prevention of diet-induced obesity. In the long term, we expect that supplementation with these compounds will also prevent age-related disease and extend the overall survival of mice. It is our hope that many of the benefits observed for mice will also hold true for humans.”

This study will be included in eLife’s Special Issue on Aging, Geroscience and Longevity. To view all articles published in the Special Issue, visit

Identification and Application of Gene Expression Signatures Associated with Lifespan Extension.

Tyshkovskiy A, Bozaykut P, Borodinova AA, Gerashchenko MV, Ables GP, Garratt M, Khaitovich P, Clish CB, Miller RA, Gladyshev VN.

Cell Metab. 2019 Sep 3;30(3):573-593.e8. doi: 10.1016/j

PMID: 31353263 

Several pharmacological, dietary, and genetic interventions that increase mammalian lifespan are known, but general principles of lifespan extension remain unclear. Here, we performed RNA sequencing (RNA-seq) analyses of mice subjected to 8 longevity interventions. We discovered a feminizing effect associated with growth hormone regulation and diminution of sex-related differences. Expanding this analysis to 17 interventions with public data, we observed that many interventions induced similar gene expression changes. We identified hepatic gene signatures associated with lifespan extension across interventions, including upregulation of oxidative phosphorylation and drug metabolism, and showed that perturbed pathways may be shared across tissues. We further applied the discovered longevity signatures to identify new lifespan-extending candidates, such as chronic hypoxia, KU-0063794, and ascorbyl-palmitate. Finally, we developed GENtervention, an app that visualizes associations between gene expression changes and longevity. Overall, this study describes general and specific transcriptomic programs of lifespan extension in mice and provides tools to discover new interventions.

The dietary switch that may boost longevity and its correlation to SAAR

The dietary switch that may boost longevity and its correlation to SAAR

A new epidemiological study published in The BMJ explores the association between eating red meat and the risk of death, specifically how risk of death can be lessened through dietary change—decreasing red meat consumption while increasing intake of healthier animal and plant-based foods. This correlates with OFAS research in rodents demonstrating that a sulfur amino acid-restricted (SAAR) diet can increase lifespan and delay onset of age-related diseases. In general, meat and other animal-based food sources have high SAA while plant-based food sources such as vegetables, legumes, whole grains, and fruits have low SAA.

The study looked to produce evidence backing previous studies showing “that higher red meat consumption, especially processed red meat, is associated with an increased risk of type 2 diabetes, cardiovascular disease, certain types of cancer, including colorectal cancer, and mortality.” Analyzing data from a cohort of 81,469 US health professionals (male and female) from a 16-year period, this study found 1) increases in red meat consumption, especially processed meat, are associated with a higher risk of death and 2) decreases in red meat consumption and simultaneous increases in healthy alternative food choices over time are associated with a lower mortality risk, further supporting the health benefits of replacing red and processed meat with healthy protein sources, whole grains, or vegetables.

To read the full article, click here

Zheng Yan, Li Yanping, Satija Ambika, Pan An, Sotos Prieto Mercedes, Rimm Eric et al. Association of changes in red meat consumption with total and cause specific mortality among US women and men: two prospective cohort studiesBMJ 2019; 365 :l2110

Researchers Find Reversible Cause of Vascular Aging

Researchers Find Reversible Cause of Vascular Aging

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.