The Principles and Practice of Antiaging Medicine for the Clinical Physician
Shils ME, Olson JA. Modern Nutrition in Health and Diseases. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999: 573–603.
*H-Scan from Hoch Company; see Resource section at the end of the book.
4
DNA: The Core of Our Aging Blueprint
Vincent C. Giampapa, M.D., F.A.C.S. Ronald Pero, Ph.D.
When you teach your son, you teach your son’s son.
Within each of the 100 trillion cells that make up the human body is a specific area termed the nucleus, or control center, of the cell. Within each nucleus, there are so many base pairs of the DNA that if they were laid end to end, there would be trillions of miles of DNA within each person (Diagram IV-1).
Primer of Basic Genetics for the Aesthetic Surgeon and Physician
Within the nucleus, there exists one set of genes passed on from the mother and one set from the father. Each complete pair includes approximately 30,000 to 80,000 genes. People inherit one copy of each set of these genes from each parent. The process of combining these sets from both the mother and father is referred to as recombination.
The human genome has been compared by a number of authors to a book. If the human genome is described in this manner, the description may be as follows:
1. The human genome is composed of 23 chapters called chromosomes.
2. Each chapter contains several thousand stories. These stories are called genes.
3. Each story is made up of paragraphs called exons, which are interrupted by advertisements, or introns.
4. Each paragraph also contains other words, called codons.
5. Each word is written in letters, called bases. There are four bases, which consist of these words: adenine, cytosine, guanine and thymine,
6. Each chromosome can be considered a pair of extremely long DNA molecules.
7. The human genome, under the correct conditions, can both read and “photocopy” itself. The photocopying process is known as replication, and the reading process is known as translation.
8. The base pairs bond to each other in a complementary manner1: Adenine (A) always binds with thymine (T), and guanine (G) always binds with cytosine (C). In order for a single strand of DNA to copy itself, it constructs a complementary strand with all the Ts opposite all the As and all the Gs opposite all the Cs. In this manner, replication is accomplished.
9. Transcription, on the other hand, is a process by which the information of a gene is transcribed into a copy by the same base pairing combination. The process of transcription makes RNA and not another molecule of DNA. This molecule is very similar in chemical structure to DNA; the only difference is that RNA contains uracil (U) in place of thymine.
The RNA copy form is called messenger RNA. At this point, removal of all the introns, and the splicing together of all the exons, modifies it. Messenger RNA is then transported out of the nucleus and into the “cellular soup,” or extracellular fluid. A molecular machine referred to as a ribosome, which is also made partly of RNA, moves along the messenger RNA, translating each three-letter codon, or sequence of base pairs. Messenger RNA functions with a different alphabet made of 23 amino acids. At this stage, messenger RNA interacts with transfer RNA. As each amino acid is produced by the messenger RNA and transfer RNA complex, it is attached to the other newly produced amino acids in order to form a chain in the same order as the codons were positioned on the original messenger RNA molecule. When the whole message from the messenger RNA has been translated, this long chain of amino acids folds three-dimensionally upon itself into a characteristic shape.
These folded amino acid sequences are now known as proteins. It is essential to understand the importance of proteins. The complete body is primarily made up of proteins or its processes which are governed by proteins. Also, in essence, every protein is a translated gene.
Proteins called enzymes catalyze the body’s chemical reactions. Proteins are also responsible for switching genes on and off—stimulating or inhibiting their action—by physically attaching themselves to the promoters’ or enhancers’ regions near the start of the genes themselves. Different genes are switched on and off during different periods of a person’s life and in different parts of the body.
When different parts of the gene are copied mistakenly or a certain sequence of these genetic letters is left out, the result is known as a mutation.
It is important to keep in mind that aside from the nucleus, which contains these 23 pairs of chromosomes from the mother and father, other genes are also present outside the nucleus within the cellular organelle called a mitochondrion. The mitochondrial genes are inherited only from the mother. Therefore, humans are slightly more like their mothers than like their fathers with regard to genetic makeup.
Not all genes appear to be made of DNA. Some viruses use RNA instead. Certain genes do not produce protein. Some genes are transcribed into RNA and not into protein. This type of RNA may form part of the ribosome or part of transfer RNA. Some reactions within the cell are catalyzed by RNA instead of by proteins. Some of the three-letter codons specify start or stop commands as well. This information is useful in the continuing discussion concerning DNA, the core of our aging blueprint. A detailed account of this information is available in Molecular Cell Biology, by Harvey Lodish.2 First, there are a few important points to be emphasized.
Genes act as repositories of coded information for the synthesis of proteins, enzymes and, eventually, hormones. Some of these key proteins actually regulate the repair of DNA or determine which segments of genes are functioning, or active, at a specific time. This determination is referred to as gene expression.
Specific environmental agents, such as radiation, sun exposure and pollution, can modify how all of these genetic characteristics are actually expressed or activated.
The fundamental goal of anti-aging therapy is to manipulate gene expression as it relates to the healthy maintenance of structure and function of an individual as he or she ages.
Laboratory analysis has documented the relative content of the human genetic structure (Diagram IV-2):
1. 22% of DNA is devoted to RNA and protein synthesis.
2. 12% is devoted to cellular division.
3. 12% controls cell signaling and communication.
4. 12% is directly related to immune function.
5. 17% affects cell metabolism.
6. 8% is responsible for cellular cytostructure.
7. 17% has no known function. This portion of DNA has been termed junk DNA by research scientists at present. It is not actually “junk”; its purpose is simply not yet understood. Theories of junk DNA have evolved and included the concept that this extra DNA may be simply leftover DNA from humans’ evolutionary past, or perhaps it may be redundant repeat units, which function as extra codes3–5a (Diagrams IV-3 and IV-4). Other theorists state that this junk DNA may actually