A Genetic Explanation for the Process of Aging
Sam Neff ’21 / Biological Sciences, News, Fall 2017 / September 24, 2017
Genes direct the process of autophagy, a cellular degradation mechanism that is essential for destroying dysfunctional proteins, but can go awry as an organism ages.
(Source: Wikimedia Commons)
A recent study from the Institute of Molecular Biology in Mainz, Germany examining the genome of the nematode C. elegans has yielded a significant discovery. Researchers studied certain aging-related genes with far-reaching implications, from a better understanding of the aging process in the context of evolutionary development to a potential target for treating neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and ALS (1).
From an evolutionary standpoint, the process of aging is paradoxical. Processes that result in the death of cells and ultimately the death of the organism don’t appear to fall in line with the idea that natural selection conserves the most beneficial genetic traits. In 1953, biologist George C. Williams proposed the idea of antagonistic pleiotropy: certain genes benefit reproductive success, but also contribute to the aging process later on in life. The adverse aging effects do not occur until after the animal reproduces, and thus, the genes are passed down over generations (1). The recent study published in Science Daily provides the first evidence for such genes.
The specific cellular process under the influence of these genes is called autophagy. The process entails the capture and subsequent degradation of cellular components by so-called autophagosomes and lysosomes. In young organisms, the process is essential for destroying misshapen and ill-functioning proteins. Over time, however, autophagy becomes dysfunctional, leading to death on the cellular level and disease of the organism (2).
Researchers at the Institute of Molecular Biology altered the regulation of autophagic genes in C. elegans. The team of scientists found that signals regulating cellular aging arose from neurons expressing the autophagy genes, and that by inactivating the autophagy genes in these cells, the neurons – and the muscles and other tissues that they control – function in a healthier manner (1,2).
Because the action of autophagic genes in neurons has an effect on parts of the body connected to the neural network, it is thought that disabling autophagic genes in patients with neurodegenerative disorders may be beneficial. The underlying causes of these diseases are uncertain, and autophagy may play a role, if not the defining role, in their progression.
Although the study species is a nearly-microscopic worm, its genetic composition is not altogether different from that of humans. In fact, C. elegans is closely related to all vertebrate species via a common ancestor, and many of the worm’s developmental genes are present throughout the vertebrate lineage as well. This means that the processes of aging identified in the worm C. elegans may be very similar to aging processes of humans (3).
Thomas Wilhelm of the Mainz study describes the potential of these findings to improve the quality and duration of life: “Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age who you then live longer than, that’s what it’s like for the worms. We turn autophagy off only in one tissue and the whole animal gets a boost. The neurons are much healthier in the treated worms and we think this is what keeps the muscles and the rest of the body in good shape. The net result is a 50% extension of life.”
Perhaps targeting autophagy genes will lead to a remarkable extension of the human life span. Maybe there are other genes involved in the aging process yet to be identified. The answers to these questions await further research.
References:
(1) Johannes Gutenberg Universitaet Mainz. (2017, September 15). Why we did not evolve to live forever: Unveiling the mystery of why we age. Science Daily. Retrieved September 21, 2017 from <www.sciencedaily.com/releases/2017/09/170915144151.htm>
(2) Thomas Wilhelm, Jonathan Byrne, Rebeca Medina, Ena Kolundžić, Johannes Geisinger, Martina Hajduskova, Baris Tursun, Holger Richly. (2017). Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans. Genes & Development, 2017; 31 (15): 1561 DOI: 10.1101/gad.301648.117
(3) Lundquist, Erik. What is C. Elegans and why do scientists use it to study disease. The University of Kansas. Retrieved September 23, 2017 from <http://www.people.ku.edu/~erikl/Lundquist_Lab/Why_study_C._elegans.html>