Researchers uncover genetic basis of natural variation in aging rate

November 10, 2017, Chinese Academy of Sciences

Aging is characterized by a progressive decline in physiological functions and is a major risk factor for neurodegenerative disorders, cancer and diabetes. Previous studies on aging mainly focused on the regulation of longevity, and more than 100 genes and numerous small compounds have been identified that regulate lifespan in organisms from yeast to mammals.

Lifespan extension induced by genetic mutations has been shown in recent studies not to delay age-related behavioral decline, suggesting that longevity and behavioral aging may be two dissociable processes. With the increase of life expectancy, prevention of age-related functional impairment has emerged as a major challenge. Despite the great advances in genetic control of animal lifespan, little was known about the regulatory mechanisms of , i.e., aging with limited loss of physiological function.

Now, a new study carried out by researchers from Dr. CAI Shiqing's lab at the Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences has uncovered a genetic basis for in aging rates. The study was published in Nature.

The rate of aging is highly variable among individuals. It is believed that this variation is governed by environmental and genetic factors. Despite great interest in studying natural variation in aging rates to identify factors that control healthy aging, no such factor had been found. In order to explore this question, researchers from Dr. CAI Shiqing's lab studied the genetic origin of variability in the rate of aging using Caenorhabditis elegans as an animal model.

C. elegans is a tiny, free-living nematode, about 1 mm in length. Due to its short lifespan and clear genetic background, C. elegans has been widely used in aging research. Many conserved longevity pathways were first identified in C. elegans.

Natural isolates of C. elegans from different parts of the world were shown in this research to have distinct rates of decline in virility, feeding behavior and locomotion during aging. The researchers found that genetic variations in a novel neuropeptide coding gene (rgba-1) and its receptor gene npr-28 regulate the aging rate of worm behavior among wild isolates.

RGBA-1 from glial cells activates NPR-28 signaling in serotonergic and dopaminergic neurons to regulate behavioral decline in aging animals. The function of RGBA-1/NPR-28 signaling on behavioral aging depends on SIR-2.1-mediated activation of the mitochondrial unfolded protein response, a pathway known to modulate aging.

The researchers also performed population genetic analysis of rgba-1 and npr-28 and found that the two might have been subjected to a recent selective sweep, a natural selection process that leads to the reduction or elimination of genetic variations among individuals.

This study reveals the first genetic pathway underlying natural variation in the rate of aging, and uncovers the important role of neuropeptide-mediated glia-neuron signaling in controlling the aging rate. Further studies on natural variation in the rate of aging will pave the way for a comprehensive understanding of the biological regulation of healthy aging.

The antagonistic pleiotropy theory of the evolution of aging, proposed by George Williams in 1957, suggested that naturally selected genes promote survival and reproductive success in early life, but accelerate aging in later life. In contrast, this study suggests that the evolutionary selection of genes that offer benefits in early life could also result in a concomitant extension of lifespan or extension of health span, or both.

This research indicates that aging rates may have been affected by the emergence of new genes, natural selection, and interaction between different genetic loci, thus providing new insights into the evolutionary theory of aging.

Explore further: Researchers identify patterns of protein synthesis associated with increased longevity

More information: Jiang-An Yin et al, Genetic variation in glia–neuron signalling modulates ageing rate, Nature (2017). DOI: 10.1038/nature24463

Related Stories

Researchers identify patterns of protein synthesis associated with increased longevity

February 23, 2017
Aging is a complex process that involves multiple metabolic and regulatory pathways. Previous studies have identified hundreds of genes whose deletion can significantly increase lifespan in model organisms. Yet, how these ...

Yeast mutants unlock the secrets of aging

January 31, 2017
Yeast—it's more than just a fungus. It can also tell us a lot about growing older.

RNA and longevity: Discovering the mechanisms behind aging

March 9, 2017
The vigors of youth and the greener pastures of yesteryears. Some might refer to these and other similar clichés as nothing more than rose-tinted literations of the past; a cognitive side effect of life. Romanticizing collective ...

Recommended for you

LincRNAs identified in human fat tissue

June 21, 2018
A large team of researchers from the U.S. and China has succeeded in identifying a number of RNA fragments found in human fat tissue. In their paper published in the journal Science Translational Medicine the group describes ...

Scientists solve the case of the missing subplate, with wide implications for brain science

June 21, 2018
The disappearance of an entire brain region should be cause for concern. Yet, for decades scientists have calmly maintained that one brain area, the subplate, simply vanishes during the course of human development. Recently, ...

Key molecule of aging discovered

June 21, 2018
Every cell and every organism ages sooner or later. But why is this so? Scientists at the German Cancer Research Center in Heidelberg have now discovered for the first time a protein that represents a central switching point ...

Compound made inside human body stops viruses from replicating

June 20, 2018
The newest antiviral drugs could take advantage of a compound made not by humans, but inside them. A team of researchers has identified the mode of action of viperin, a naturally occurring enzyme in humans and other mammals ...

Research reveals zero proof probiotics can ease your anxiety

June 20, 2018
If you're expecting probiotics to reduce your anxiety, it might be time to put down that yogurt spoon—or supplement bottle—and call a professional instead.

Long-term estrogen therapy changes microbial activity in the gut, study finds

June 20, 2018
Long-term therapy with estrogen and bazedoxifene alters the microbial composition and activity in the gut, affecting how estrogen is metabolized, a new study in mice found.

0 comments

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.