Genes for Healthy Aging Found

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.

In addition to the genes associated with longevity, say Chinese scientists, there are genes associated with age-related behavioral decline. The scientists decided to substantiate this assertion by studying differences in the rate of aging in wild strains of Caenorhabditis elegans, while also measuring the rates of age-related decline in traits associated with mating, feeding, and locomotion. Ultimately, the scientists determined that polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioral-aging-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline in mating and feeding traits.

Detailed results appeared in the journal Nature, in an article entitled “Genetic Variation in Glia–Neuron Signalling Modulates Ageing Rate.” This study reveals the first genetic pathway underlying natural variation in the rate of aging, and it uncovers the important role of neuropeptide-mediated glia–neuron signaling in controlling the aging rate.

“Glia-derived RGBA-1 activates NPR-28 signalling, which acts in serotonergic and dopaminergic neurons to accelerate behavioural deterioration,” wrote the article’s authors. “This signalling involves the SIR-2.1-dependent activation of the mitochondrial unfolded protein response, a pathway that modulates ageing.”

The study was led by Shi-Qing Cai, Ph.D., and colleagues at the Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences. These scientists maintain that their work suggests a genetic mechanism underlying natural variation in the rate of ageing and provides insight into the biological regulation of healthy aging.

In their article, the scientists referred to the antagonistic pleiotropy theory of the evolution of aging, which was proposed by George Williams, Ph.D., then at the University of Michigan, in 1957. According to this theory, naturally selected genes promote survival and reproductive success in early life, but accelerate aging in later life. In contrast, the current 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 healthspan, or both.

Aging rates, the authors of the current study propose, 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.

The authors also acknowledged that aging variation among populations may have complex genetic bases. RGBA-1–NPR-28 signaling, they noted, affects only some aspects of healthy aging; it had little effect on the lifespan and age-dependent decline in locomotion.

“Further study of long-lived C. elegans wild strains that preserve physiological functions into their late adulthood,” the authors concluded, “will extend our understanding of the biological regulation of healthy ageing.”

“A major remaining challenge is to determine whether neuropeptides have a similar role in regulating healthy lifespan in humans,” added the Georgia Institute of Technology’s Patrick T. McGrath, Ph.D. “Neuropeptide receptors are members of the G-protein-coupled receptor family, which are often targeted by drugs in the treatment of disease,” he indicated in a News and Views editorial that accompanied the Nature article. “Focusing on neuropeptide signalling in human ageing could lead to the development of drugs that ameliorate ageing-related declines in health.”