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
First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife
Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
25.10.2016 | Earth Sciences
25.10.2016 | Power and Electrical Engineering
25.10.2016 | Process Engineering