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.”
As we begin the new year, we at the Orentreich Foundation for the Advancement of Science (OFAS) wish to thank our friends around the globe for their continued support. To view our recently published 2020 Report of Directors, click here.
We hope you will consider investing in OFAS’s research efforts with a donation. With each day that passes, advancements are made toward the goal of extending healthy lifespan, and each day OFAS is able to be a part of this work because of friends like you.
Thank you for your part in making OFAS’s 2020 such a success!
Methionine restriction (MR) prevents obesity because of a futile lipid cycle in which two metabolic pathways run simultaneously in opposite directions and have no overall effect other than to dissipate energy in the form of heat. In this study, we show that MR promotes weight loss not just by this futile lipid cycle, but also by a coordinated response that involves apoptosis (normal cell death) and autophagy (a metabolic process by which the body consumes its own tissue) to maintain physiological equilibrium.
It has been observed that the hormones adiponectin and fibroblast growth factor 21 are consistently elevated during MR. To clearly define the roles of ADIPOQ and FGF21 during MR, we used mice that lacked either or both hormones. The obese mice, once placed on an MR diet, lost weight regardless of the presence of these hormones, demonstrating that neither is essential to reduce fat during MR.
Cooke, D., Mattocks, D., Nichenametla, S. N., Anunciado‐Koza, R. P., Koza, R. A., & Ables, G. P. (2020). Weight Loss and Concomitant Adipose Autophagy in Methionine‐Restricted Obese Mice is Not Dependent on Adiponectin or FGF21. Obesity.
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.
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
It is with profound sadness that we announce the recent passing of our Founder and Co-Director, Dr. Norman Orentreich. Dr. O, as he was known to staff, was a visionary and a charismatic leader who brought a remarkable passion and energy to his work and research. An inspiration both professionally and personally, he will be dearly missed.
Since 2005, Dr. David Orentreich has served with his father as Co-Director of the Foundation. Now under his sole directorship, we will honor the life of Dr. O by continuing the mission he laid out on founding OFAS in 1961: biomedical research that prevents, halts, or reverses those disorders that decrease the quality or length of life.
Human health, diet, and environmental sustainability are prevailing concerns that share many common uncertainties. Fulfilling the nutritional needs of a growing population while limiting environmental degradation is a critical challenge that requires global collaboration and commitment. Current food systems, in addition to supporting unhealthy diets and practices, greatly impact the environment, leading to climate change, biodiversity loss, freshwater misuse, interference with the global nitrogen and phosphorus cycles, and land-system change. Current global food systems are simply unable to provide the population of ~7.7 billion with healthy diets while also achieving environmental sustainability.
The EAT-Lancet Commission brings together scientists and experts from the diverse fields of human health, agriculture, political sciences, and environmental sustainability in an effort to establish global targets for healthy diets and sustainable food production. Using the best scientific evidence available, the Commission seeks a global transformation of food systemsthat will help to achieve the goals set forth in the UN Sustainable Development Goals (SDGs) and the Paris Agreement. The SDGs are global goals reduce hunger and improve nutrition. The Paris Agreement sets a budget on greenhouse gas emissions to keep the global mean temperature increase to less than 2°C.
The EAT-Lancet Commission has quantitatively characterized a universal healthy reference diet that will positively impact both human health and the environment. This healthy reference diet consists predominantly of vegetables, fruits, whole grains, legumes, and unsaturated oils; includes a low to moderate amount of seafood and poultry; and includes no or little red meat, processed meat, added sugar, refined grains, and starchy vegetables. The commission has also rendered scientific boundaries that will aid in the reduction of environmental degradation caused by food production at all scales.
At OFAS, we have spent over 25 years studying how a low-methionine diet improves lifespan and healthspan. This diet consists primarily of vegetables, fruits, whole grains, and legumes and contains limited quantities of meats, seafood, and poultry—much like the the EAT-Lancet Commission’s healthy reference diet. Thus, a low methionine diet not only provides benefit to an individual’s health but also promotes a sustainable environment.
The EAT-Lancet Commission proposes five strategies to achieve the “Great Food Transformation”.
1. Seek international and national commitment to shift towards healthy diets
2. Reorient agricultural priorities from producing large quantities of food to producing healthy food
3. Sustainably intensify food production, generating high-quality output
4. Strong and coordinated governance of land and oceans
5. At least halve food loss and waste, in line with global SDGs
Willett, W., Rockström, J., Loken, B., Springmann, M., et.al. 2019. Food in the Anthropocene: the EAT–Lancet Commission on healthy diets from sustainable food systems. EAT-Lancet EAT–Lancet Commission on healthy diets from sustainable food systems DOI: 10.1016/S0140-6736(18)31788-4
Ables, G.P., and Johnson, J.E. (2017). Pleiotropic responses to methionine restriction. Exp Gerontol 94, 83-88.