Scientists identify molecular process in fat cells that influences stress and longevity

September 26, 2012
C. Ronald Kahn, M.D., is Chief Academic Officer at Joslin Diabetes Center and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. Credit: John Soares

As part of their ongoing research investigating the biology of aging, the greatest risk factor for type 2 diabetes and other serious diseases, scientists at Joslin Diabetes Center have identified a new factor—microRNA processing in fat tissue—which plays a major role in aging and stress resistance. 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, secrete a number of substances that actively influence metabolism and . 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 , mice and C. elegans (a used as a 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 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.

, 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 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.

Explore further: Scientists identify important mechanism that affects the aging process

Related Stories

Scientists identify important mechanism that affects the aging process

May 1, 2012
Scientists at Joslin Diabetes Center have identified a key mechanism of action for the TOR (target of rapamycin) protein kinase, a critical regulator of cell growth which plays a major role in illness and aging. This finding ...

Tale of 2 mice pinpoints major factor for insulin resistance

May 16, 2011
The road to type 2 diabetes is paved with insulin resistance, a condition often associated with obesity in which the hormone begins to fail at its job helping to convert sugars to energy. Researchers at Joslin Diabetes Center ...

Explaining heart failure as a cause of diabetes

January 3, 2012
Either heart failure or diabetes alone is bad enough, but oftentimes the two conditions seem to go together. Now, researchers reporting in the January Cell Metabolism appear to have found the culprit that leads from heart ...

Recommended for you

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

Study finds immune system is critical to regeneration

September 20, 2017
The answer to regenerative medicine's most compelling question—why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot—may lie with the body's innate immune system, ...

Immune cells produce wound healing factor, could lead to new IBD treatment

September 20, 2017
Specific immune cells have the ability to produce a healing factor that can promote wound repair in the intestine, a finding that could lead to new, potential therapeutic treatments for inflammatory bowel disease (IBD), according ...

As men's weight rises, sperm health may fall

September 20, 2017
(HealthDay)—A widening waistline may make for shrinking numbers of sperm, new research suggests.

New model may help science overcome the brain's fortress-like barrier

September 19, 2017
Scientists have helped provide a way to better understand how to enable drugs to enter the brain and how cancer cells make it past the blood brain barrier.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

JVK
1 / 5 (1) Sep 26, 2012
"miRNAs: effectors of environmental influences on gene expression and disease" http://www.ncbi.n...18281715

Abstract excerpt: "Lastly, we identify new exciting avenues of research on the role of miRNAs in toxicogenomics and the possibility of epigenetic effects on gene expression."

Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338. http://dx.doi.org...i0.17338

The epigenetic effects of food odors are what cause us to eat too much and increase the secretion of substances from fat cells that "actively" influence metabolism and systemic inflammation. The "active" influence of fat cells results from epigenetic effects on intracelllular signaling and stochastic gene expression.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.