The error catastrophe theory of aging states that aging is the result of the accumulation of errors in cellular molecules that are essential for cellular function and reproduction that eventually reaches a catastrophic level that is incompatible with cellular survival. The central dogma of molecular biology refers to the unidirectional transfer of genetic information from deoxyribonucleic acid (DNA) to proteins. DNA carries all of the cells genetic information and instructions for carrying out the functions of the cell. Proteins serve a variety of functions. Some proteins serve in metabolic or structural processes, while others serve to catalyze cellular reactions.

The transfer of genetic information from DNA to protein occurs in a series of coordinated processes. The first process called transcription involves the transfer of genetic information from double‐stranded DNA to single‐stranded messenger ribonucleic acid (mRNA) that is able to transport this information from inside the nucleus of the cell, where DNA is housed, to the cytoplasm that surrounds the nucleus, where protein will be made. After this mRNA copy of the DNA is created, the mRNA leaves the nucleus for the cytoplasm and protein is synthesized through a process called translation. Once synthesized, these proteins fold into a three‐dimensional form with grooves that can allow specific molecules to bind. The unique structure of the molecules formed, allow proteins to serve as enzymes that catalyze essential chemical reactions in the cell, including those reactions involved in transcription and translation. For example, RNA polymerase II is the protein (enzyme) responsible for the initiation of DNA transcription, and the aminoacyl transfer RNA (tRNA) synthetases are group of enzymes that catalyze the addition of amino acids (the building blocks of proteins) to tRNA molecules during protein translation.

The error catastrophe theory of aging was proposed by Leslie Orgel in 1963. This theory is based on the assumption that transcription and translation are inexact processes that will result in a small, but potentially cumulative amount of error. Orgel proposed that these errors would accumulate with age until reaching a catastrophic level at which the organism could no longer sustain life.

Consequences of Error Accumulation

Errors that occur during transcription or translation may result in misincorporation of amino acids into proteins, or errors in the protein sequence that may lead to a spectrum of structural and functional alterations of the protein and the cell. Some errors may not affect the final protein sequence; if the change resulted in a duplicate code for an amino acid, then no misincorporation will occur. Other errors that do lead to a change of amino acid may result in the misincorporation of an amino acid, but if it is one of similar structure, the protein molecule may still be fully functional, because the error did not effect the folding of the protein molecule, or may be in a location other than the protein's active site (the space where other molecules bind during chemical reactions). Errors that lead to the incorporation of incorrect amino acids that are dissimilar to the appropriate amino acid, or changes in the amino acids that line the groove/active site of the protein may potentially alter its affinity of the protein for its substrate (the specific molecule that the protein is designed to bind to), leading to a significant change in the function of the protein.

Because proteins are eventually degraded, if errors occur in a protein serving a metabolic or structural function, there may be some level of cellular dysfunction, but when these proteins are removed, the evidence of this error will be lost. If however this error occurs in a protein molecule involved in transcription or translation, more errors will be produced with each step, leading to an exponential increase in the error rate as successive molecules are produced. These errors and dysfunctional molecules would eventually accumulate in the cell, reaching a threshold where an error catastrophe would occur. At this point the cell can no longer function and cell death would ensue.

Public Health Perspective

Although some scientific investigations have provided evidence of the accumulation of altered proteins with aging, these changes have been attributed to posttranslational modifications of the proteins, instead of transcriptional and translational errors. There were no alterations in the amino acid sequences of these proteins that would suggest errors in protein manufacturing. Other research has documented that while the fidelity of protein synthesis may be less than that of DNA, it remains relatively constant over time. Although this theory has been discounted based on available scientific evidence, there is still much left to be explained, for example, the accuracy of protein synthesis in young and old and the threshold at which errors may lead to cellular dysfunction. Filling these gaps in knowledge may elucidate the role of protein error in aging, which may ultimately have important implications for public health and aging.

Related Topics

Accumulative waste theory of aging, Anti‐aging remedies, Cellular theory of aging, Life expectancy