This finding may lead to the development of treatments that increase stress resistance and longevity and improve metabolism. The findings appear in the September 5 online edition of Cell Metabolism.
Over the past several years, it has become clear that fat cells (adipocytes) are more than just repositories to store fat. Indeed, fat cells secrete a number of substances that actively influence metabolism and systemic inflammation. Previous studies have found that reducing fat mass by caloric restriction (CR) or surgical or genetic means can promote longevity and stress resistance in species from yeast to primates.
However, little is known about how CR and fat reduction produce these beneficial effects. This study investigated one type of molecular mediator – change in microRNAs (miRNAs) and the processing enzymes required to make them– that is influenced by aging and reversed by caloric restriction. miRNAs are involved in the formation of mature RNA.
Based on studies conducted using human cells, mice and C. elegans (a microscopic worm used as a model organism for aging studies), the researchers demonstrated that levels of multiple miRNAs, decrease in fat tissue (adipose) with age in all three species. This is due to a decrease in the critical enzyme required from converted pre-miRNAs to mature miRNAs, Dicer. In the human study, which compared the miRNA levels in preadipocytes (fat cell precusors) of young, middle-aged and older people, people aged 70 and older had the lowest miRNA levels. “The fact that this change occurs in humans, mice and worms points to its significance as a general and important process,” says lead author C. Ronald Kahn, MD, Chief Academic Officer at Joslin Diabetes Center and the Mary K. Iacocca Professor of Medicine at Harvard Medical School.
Caloric restriction, which has been shown to prolong lifespan and improve stress resistance in both mice and worms, prevents this decline of Dicer, and in the case of the mice, restore miRNAs to levels observed in young mice. Conversely, exposure of adipocytes to major stressors associated with aging and metabolic diseases, including toxic agents, Dicer levels decreased. Mice and worms engineered to have decreased Dicer expression in fat showed increased sensitivity to stress, a sign of premature aging. By contrast, worms engineered to “overexpress” Dicer in the intestine (the adipose tissue equivalent in worms) had greater stress resistance and lived longer.
Overall, these studies showed that regulation of miRNA processing in adipose-related tissues plays an important role in longevity and an organism’s ability to respond to age-related and environmental stress. “This study points to a completely new mechanism by which fat might affect lifespan and is the first time that anyone has looked at fat and miRNAs as factors in longevity,” according to co-author T. Keith Blackwell, MD, PhD, co-head of Joslin's Section on Islet Cell and Regenerative Biology and Professor of Pathology at Harvard Medical School.
Based on this study, Blackwell suggests that “finding ways to improve miRNA processing to keep miRNA levels up during aging might have a role in protecting against the stresses of everyday life and the development of age- and stress-related disease.”
Dr. Kahn and the study investigators are currently working on ways to genetically control Dicer levels in the fat tissues of mice, to create mouse models that are more or less resistant to stress. “We would love to find drugs that would mimic this genetic manipulation to produce a beneficial effect,” says Dr. Kahn. “If we can better understand the biology of aging, we might also understand how age impacts diabetes,” says Kahn.
Study co-authors include Marcelo A. Mori, Prashant Raghavan, Jeremie Boucher, Stacey Robida-Stubbs, Yazmin Macotela, Steven J. Russell, and T. Keith Blackwell of Joslin; and James L. Kirkland and Thomas Thomou of the Mayo Clinic.
About Joslin Diabetes Center
Joslin Diabetes Center, located in Boston, Massachusetts, is the world's largest diabetes research and clinical care organization. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School.
Our mission is to prevent, treat and cure diabetes. Our vision is a world free of diabetes and its complications.
Jeffrey Bright | Newswise Science News
Complete skin regeneration system of fish unraveled
24.04.2018 | Tokyo Institute of Technology
Scientists generate an atlas of the human genome using stem cells
24.04.2018 | The Hebrew University of Jerusalem
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
24.04.2018 | Information Technology
24.04.2018 | Earth Sciences
24.04.2018 | Life Sciences