OFAS Associate Scientist Dr. Sailendra Nichenametla will chair a webinar, “Sulfur Amino Acid Restriction – Moving from Animals to Humans”, for Aging Science Talks on October 20-21, 2021. The sessions will include presentations by Dr. Nichenametla, OFAS Associate Scientist Dr. Jay Johnson, and OFAS Assistant Scientist Dr. Zhen Dong. Dr. John P. Richie, Jr., (Penn State University College of Medicine), a member of OFAS’s Board of Scientific Advisors, will also be among the presenters. The complete program, including information on attending the Zoom sessions, is available here.
This series of talks was begun in March 2020 in response to the COVID-19 pandemic as a means of keeping aging researchers connected at a time when scientific conferences were being cancelled around the world. The talks have continued in webinar format with the support of the Glenn Foundation for Medical Research. For more information about the Aging Science Talks series, including dates and topics of upcoming talks, click here.
Researchers from Mayo Clinic have uncovered a novel way in which exercise may contribute to healthy aging by suppressing an age-related phenomenon known as the senescence-associated secretory phenotype, or SASP.
In recent years, research has uncovered a number of factors that contribute to or are present in the pathology of aging; among them, the SASP has gained a good deal of attention as a causal and potentially treatable contributor to the diseases of aging. Cellular senescence was first observed by Leonard Hayflick in 1965 and is characterized as a condition wherein a viable cell is no longer able to divide. As a result, cellular senescence is thought to act as a potential anti-cancer mechanism. Further, cellular senescence can result from a number of aberrant processes, including oxidative damage, mitochondrial dysfunction, telomere dysfunction, DNA damage/mutation, transcriptional dysregulation, and epigenetic dysregulation. Senescent cells have been observed to secrete a number of inflammatory hormones, and have therefore been implicated in driving what has been described as “inflamm-aging”, whereby chronic and unchecked inflammation leads to disease. These insights have led to a number of potentially promising interventions designed to remove or suppress senescent cells, referred to as senolytic or senomorphic therapies, respectively.
Exercise has long been attributed to improvements in health and longevity, and it has been hypothesized that these beneficial outcomes are due to improvements in a multitude of factors, including adiposity, cardiovascular health, and mitochondrial function. In their recent Aging Cell paper, Englund et al., have provided evidence for an additional mechanism by which exercise, via suppression of the SASP, may lead to benefits in aging populations. In this study, individuals undertook a 12-week progressive strength and endurance training program. As expected, study participants saw improvements in both physical performance and body composition measurements post-intervention when compared to their pre-intervention values. Additionally, levels of circulating CD3+ T-cells (cells involved in the adaptive immune response, targeting foreign agents) derived from peripheral blood showed decreased expression of SASP-associated mRNAs. Moreover, plasma-derived proteins known to be elevated as part of the SASP showed a significant reduction post-intervention.
While the authors note that previous interventional studies suggest that exercise may influence senescent cell burden, this had yet to be assessed in older adults utilizing known biomarkers. While the scope of this study does not address the mechanism (senolytic or senomorphic) by which exercise leads to a reduction in the SASP, the researchers demonstrate that exercise is effective in reducing SASP-associated biomarkers in older adults. Usefully, these biomarkers could aid researchers in determining the efficacy of future therapeutic interventions.
A post-doctoral position at the Orentreich Foundation for the Advancement of Science (Cold Spring-on-Hudson, NY) is immediately available in Dr. Sailendra Nichenametla’s lab. Dr. Nichenametla investigates the mechanisms by which methionine restriction extends lifespan and confers metabolic benefits. The candidate will be working on a variety of methionine restriction projects associated with mechanisms, nutritional aspects, and prevention of diseases, including metabolic diseases, cancers, and proteostatic disorders. Responsibilities include generating data extensively from rodent models and occasionally from in vitro studies and specimens from clinical studies. The post-doc will perform experiments, data analysis, draft publication-quality manuscripts of their findings, assist in submitting grant proposals, and present work at scientific meetings.
- A Ph.D. with 0-2 years of post-doctoral experience.
- Demonstrable research experience in biomedical sciences and in two or more of the following areas/techniques: nutrition, aging, metabolism, immunohistochemistry, cell culture, molecular biology.
- At least one paper as first author published in a peer-reviewed biomedical journal.
- At least 1 year experience working with mice or rats.
- 2-3 years’ experience working with mouse or rat models.
- At least one paper published as first author in an aging, nutrition, or related journal.
- HPLC experience.
- Experience demonstrating surgery/dissection in mice/rats.
Please use this link to submit your application. Alternatively, you may email your application materials to firstname.lastname@example.org. You will need to upload the following files:
- Cover letter.
- Full curriculum vitae including education or other academic appointments, complete publication record, and research skills listed in detail.
- PDF of the most representative publication of your previous research.
H-1B visa sponsorship will be considered on a case-by-case basis.
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 https://elifesciences.org/collections/6d673315/aging-geroscience-and-longevity-a-special-issue.
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.
To read the full article, click here
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.