AsianScientist (Nov. 29, 2017) – Scientists have uncovered the genetic basis of behavioral aging and identified a pathway that accounts for the natural variation in aging rates among different populations. Their findings, published in Nature, could lead to a better understanding of improving health span and not just lifespan.
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.
However, recent studies have demonstrated that lifespan extension induced by genetic mutations may not necessarily delay age-related behavioral decline, suggesting that longevity could be a separate process from behavioral aging. With the increase in life expectancy, the prevention of age-related functional impairment has emerged as a major challenge.
In this study, a team of researchers led by Dr. Cai Shiqing at the Institute of Neuroscience in the Chinese Academy of Sciences’ Center for Excellence in Brain Science and Intelligence Technology 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.
The researchers showed that natural isolates of C. elegans from different parts of the world had distinct rates of decline in fertility, feeding behavior and locomotion during aging. They 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.
They also discovered that RGBA-1 from glial cells activated NPR-28 signaling in serotonergic and dopaminergic neurons to regulate behavioral decline in aging animals. When RGBA-1/NPR-28 signaling was activated by the mitochondrial unfolded protein response (a pathway known to modulate aging), behavioral decline was accelerated.
According to the authors, this is the first report of a genetic pathway underlying natural variation in the rate of aging, which simultaneously demonstrated the important role of neuropeptide-mediated glia-neuron signaling in controlling the aging rate.
The researchers also performed population genetic analysis of RGBA-1 and NPR-28 and found that the two genes 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.
The authors further noted that their study suggests that the evolutionary selection of genes offering benefits in early life could also extend lifespan or health span, or both. This is in contrast to the antagonistic pleiotropy theory of the evolution of aging proposed in 1957 by Professor George Williams, then a professor at the US’ Michigan State University, which suggested that naturally selected genes promote survival and reproductive success in early life, but accelerate aging in later life.
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 article can be found at: Yin et al. (2017) Genetic Variation in Glia–neuron Signalling Modulates Aging Rate.
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Source: Chinese Academy of Sciences; Photo: Shutterstock.
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