Enhancing Protein Production for Extended Lifespan
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Chapter 1: Understanding Proteins and Aging
The role of proteins in our bodies is extensive. As outlined on Wikipedia:
Proteins are responsible for a wide range of functions within living organisms, such as catalyzing metabolic reactions, facilitating DNA replication, responding to environmental stimuli, providing structural integrity to cells and organisms, and transporting substances.
To clarify, DNA is converted into mRNA, which is subsequently translated into chains of amino acids. These chains then fold into intricate three-dimensional structures, resulting in functional proteins.
Given the essential role proteins play in various biological processes crucial to our health, it is vital to produce the correct proteins in appropriate quantities and at the right times. Additionally, identifying and recycling defective proteins is critical in averting specific types of cellular damage.
The maintenance of this complex balance of proteins is referred to as proteostasis (protein homeostasis).
As we age, however, the maintenance of proteostasis begins to deteriorate.
Genetic mutations accumulate over time, affecting the amino acid sequences. Moreover, the mechanisms responsible for transcription and translation start to decline in efficiency. Compounding this issue, our internal protein recycling systems become less effective.
A notable illustration of this phenomenon is the formation of amyloid plaques and tau tangles in Alzheimer’s disease, which are prime examples of unwanted protein aggregates.
Aging leads to an increase in misfolded proteins and a reduction in effective protein recycling—this is a significant challenge. The breakdown of proteostasis is recognized as a primary contributor to the aging process. While other factors also influence aging, the widespread importance of proteins in our bodily functions indicates that ensuring our proteins maintain their correct three-dimensional structures could be a beneficial strategy in addressing age-related decline.
Section 1.1: The Role of RPS23 in Protein Synthesis
A crucial component in protein synthesis is RPS23, which is itself a protein that is part of ribosomes. Ribosomes are the cellular machinery that interprets the mRNA code, gathers the necessary amino acids, and assembles them into proteins.
Interestingly, certain segments of RPS23 are remarkably conserved across diverse life forms, indicating their critical evolutionary importance. Given the ribosome's function, these conserved regions likely play a significant role in protein production.
Recent research identifies a few rare deviations in hyperthermophilic archaea concerning this evolutionary conservation. Specifically, a single amino acid change—where lysine is swapped for arginine—has been noted.
This discovery is fascinating since high temperatures can be detrimental to many biological molecules. Neither DNA nor proteins thrive under heat. Could it be that these unique mutations in the archaean RPS23 enhance the accuracy of protein production?
The preliminary answer appears to be affirmative.
Using CRISPR gene-editing technology, scientists introduced the mutated form of RPS23 into model organisms, including Schizosaccharomyces pombe (yeast), Caenorhabditis elegans (roundworm), and Drosophila melanogaster (fruit fly).
This modification resulted in fewer translation errors, leading to highly accurate protein production without a decrease in overall protein levels—meaning accuracy did not compromise speed. Furthermore, the proteins produced by these modified organisms exhibited greater heat resistance.
As a result, all three organisms experienced increased lifespans, ranging from approximately 9% to 23% longer, and they began aging later. However, they did experience a developmental delay, taking longer to reach sexual maturity.
The authors suggest that this developmental delay may explain why this mutation is not more prevalent. In nature, there is significant selective pressure for organisms to reproduce early and abundantly. Additionally, the extreme environments in which these archaea thrive might have amplified the fitness advantages associated with this mutation.
In conclusion, the researchers discovered that pharmacological treatments can also enhance protein production accuracy. Substances like rapamycin, Torin1, and trametinib were shown to reduce translation errors.
Caution: It is important to note that these findings are based on studies with non-human organisms such as flies, yeast, and worms.
The error detection mechanisms employed in this research were not designed to capture every conceivable error, focusing primarily on the most common ones. Lastly, the precise mechanisms by which the mutated RPS23 functions remain unclear.
The authors advocate for further exploration of therapies aimed at enhancing translation fidelity in the context of aging and age-associated diseases, particularly neurodegenerative disorders that heavily rely on the integrity of proteostasis.
Get your proteins in order.
Chapter 2: Video Insights on Protein and Longevity
In this chapter, we delve into informative video resources that further explore the connections between protein, longevity, and health.
The first video, titled "Protein: The Muscle-Centric Approach to Longevity," discusses how protein plays a vital role in promoting longevity through muscle health and metabolic processes.
The second video, "Protein Scientist Reveals Proven Ways to Improve Longevity (Do These 6 Things)," presents actionable insights from a protein scientist on enhancing lifespan through dietary and lifestyle choices.