Humans have striven to become immortal for centuries.
This post aims to introduce the basic biology of aging in various simple and complex organisms, including humans.
We must understand the intricate molecular processes that evolve in our bodies as we grow older to live longer and age better.
It is fascinating from years in medical school to appreciate the reproduction process in mammals, especially humans. I am looking at fertilization and embryogenesis with the intricate and delicately guided change process from a newly fertilized single cell and then two-cell embryo developing to a fetus. Intriguing is that the same cells invariably differentiate into bones, cartilage, hair, and muscles that form different organs and then a baby.
As the baby grows, the cells divide and undergo differentiation under genetic guidance. The changes are profoundly influenced by the environment, sustaining and maintaining growth, hence contributing to life's long-term survival. It is intriguing to know that this growth process also contributes to the aging process.
There must be an underlying process responsible for these very intricate changes that result from the genetic blueprint that was 'patched together' from two genetically different individuals as mother and father? The quest to find answers prompted the search for a structured understanding of the biological basis for aging.
Throughout history, aging has been a battle that human beings have had to fight even when they know they may not win. There has been a giant leap in understanding the universal relationship between matter and energy about health over the last decade or so. Scientists also understood the aging process better through an inclusive and intricate understanding of universal energy (including the influence of its effects!).
Understanding the biological and molecular mechanisms that drive cellular transformation and growth. However, though aging cannot be stopped, it can influence adverse factors.
This influence and control are possible by manipulating the microcosmic environment from genetics to cell metabolism and growth through lifestyle changes that hinge on the diet, exercise, and alignment to universal energy.
INTRODUCTION
Aging, by definition, is said to be a progressive decline in the function of the cellular components of tissues, organs, and an organism over time, that eventually lead to senescence (a progressive decline in divisive power of cells) and death.
This blog post expounds on a range of factors that influence aging simplistic yet organized. It also highlights it as a multifactorial process, controlled by a genetic blueprint, inveigled by microcosmic metabolic and environmental factors. Hence, the aging process is a confluence of biology and evolution because of this complexity.
For any meaningful insight into the process of aging, it is essential to understand the fundamental concepts, including the structural and functional aspects of the genome (blueprint), which includes the gene with DNA and its complex structure and relationship with the cell.
Genes are the genetic code or blueprint generated by combining traits from both parents. It contains the master sheet of every information necessary for living cells to survive and reproduce.
In eukaryotic organisms and humans, genes contain DNA, where a particular sequence determines the functional expression of the gene they code. The function is conducted by proteins.
THE BLUEPRINT, 'THE ZIPPER' – DNA
Genes are made up of 'chips' on the strand or chain of the macromolecule in our chromosome known as De-oxy ribonucleic acid or DNA.
The DNA molecule consists of two complementary strands, one from each parent, that wind around each other like a twisted ladder (called helix). These strands are antiparallel and locked like a 'zipper.' This double strand allows the cell to make two new, identical copies by 'reading' and copying each strand separately in a process known as replication.
The structure of these strands comprises a backbone of the alternating macromolecules called nucleotides. Each nucleotide consists of a nitrogenous base and molecules of the sugar deoxyribose and a phosphate group. There are four nitrogenous bases in human DNA, Guanine, Cytosine, Thymine, and Adenosine, represented as GCTA.
It is crucial to understand that every function, regulatory or otherwise, and most structural components of the human cell, tissue, and organ, are composed of proteins.
Proteins are the ultimate complex configuration of a chain of amino acids, which in their simplest form are known as peptides and polypeptides depending on their length. So, a simple polypeptide chain consists of linked amino acids in a sequence determined by genes.
The genetic codes (or gene), which are responsible for synthesizing any polypeptide chain and protein needed for the protein-mediated activity or structure, comprise a consecutive strand of three complementary bases in the region of DNA, each called a codon. The codon determines the program to generate a specific amino acid.
Hence, the amino acid sequence of every protein is synthesized by codons of DNA, and the individual's genetic blueprint is transferred during fertilization and propagated with growth. When the body is growing by regenerating cells or repairing a tissue, the new cells are made by cell division, which involves replicating the exact copy of each DNA of the original cell to form daughter cells.
It is a process constantly going on repeatedly as cells divide to regenerate. It is performed with a high degree of accuracy, fidelity, and efficiency and was the same process that the embryo utilized to grow in utero.
As mentioned previously, the body's physiological functions are affected by various proteins, either as membrane components or enzymes; hence, proteins participate in the body's structural and functional microcosm.
UNDERSTANDING POLYPEPTIDES & PROTEINS
Proteins are a complex coiled chain of amino acids that are products of digestion from our food. The human body uses twenty amino acids, some we can make in our body, but most come from the diet. The amino acids are chemically linked in polypeptides chains when they are straight (like insulin) but become proteins when they are exceptionally long and coil to secondary and tertiary forms.
It should be noted that these conformational changes in the polypeptide chains to form proteins are responsible for all physiological and biological functions of proteins. A good example is oxygen transportation by the iron attached to a protein molecule known as globulin found in hemoglobin, responsible for maintaining all mammalian life on our planet.
Earlier, we alluded that the amino acid sequence of every protein is synthesized using codes on the DNA segments of our genome called codons. Through a process known as transcription, the codes are copied into another type of macromolecule known as messenger Ribonucleic acid mRNA, which translates the codes/command from the DNA. mRNA carries the copy across the nuclear membrane to the cell's cytoplasm.
In the cytoplasm, another type of RNA, the transfer RNA tRNA, also produced in the nucleus but functionally in the cytoplasm, acts as 'scanners' transcribing the codons from the mRNA copy of the genetic code to form a sequence of amino acids in a continual process.
The result is the stacking of the amino acid in the sequence determined by the gene or DNA codons and thus forming polypeptides, the primary form of proteins.
It is important to note that the genetically determined sequence of the amino acid chains must be perfect for functional integrity. That is how faithful it must be to avoid disorders. An example is that just a breach leading to just one substitution of an amino acid in the beta chain of the globulin in hemoglobin causes a lifetime of Sickle cell disorders.
The polypeptides formed from translation must be modified with the help of another RNA called ribosomal RNA into the 'folded' coils of secondary, tertiary, or quaternary structure to become a structural or functional unit.
The color shade of our skin to the function of most tissues like hemoglobin in red blood cells, the secretion of growth hormone stimulating hormone, and other factors that control the phenotype or the external look are determined using these complex proteins.
The conclusion from the above is that humans and animals' unique characteristic, nature, function, and form is encoded in their genes. These delicately woven and intricate processes of translating the genetic code into expressed structural or functional manifestation ensure perfectly executed.
However, science has discovered that 'mistakes' or mutations happen, and environmental factors also affect the process. Nevertheless, it is a scientific highlight that the intricacy of genetic replication understandably calls for the maintenance of the structural integrity of the DNA blueprint itself using self-generated internal repair enzymes called DNA polymerases.
It is easy to imagine that during a lifetime of living, injuries, and repair of natural 'wear and tear,' this process continuously continues while maintaining significant replicative fidelity.
AGING
During regeneration and repair for maintenance of tissues, the average human cell can only divide by replication of the double-strand DNA into two copies and daughter cells about 40-80 times before it 'wears out' depending on tissue type.
Blood cells and epithelial cells of our skin and lining internal organs like intestines, reproductive organs, and urinary tract are constantly multiplying because of the high frequency of use, leading to high 'wear and tear.' Hence, they have the shortest span.
The regeneration process is supposed to repair and restore every tissue to its original state, thus causing no visible change. However, the limited capacity of cells to continue to divide beyond a limit causes cells to degenerate, deteriorate, and disintegrate after their programmed 'limit.'
Though there is significant fidelity in the replicative process of cell division, mutations, when they occur, are fixed by intricate innate mechanisms, as mentioned earlier, or 'overlooked' if deemed not detrimental.
However, over time, this gradual accumulation of unrepaired mutations leads to diverse types of alteration of DNA sequences, like a stretch of codes being added by mistake to one daughter cell during the replication process influencing the expression of genes, which invariably lead to wrong protein formation, altered function, and ultimately leading to cell death or apoptosis. It could also be just a point mutation etc.
The DNA damage theory of aging hence postulates that the accumulation of DNA alterations and 'mistakes' during replication results in the loss of functional fidelity of proteins hence the organelles of individual cells. This damage could also affect the nuclear genome and mitochondrial DNA.
So, in summary, failure of genomic fidelity to replicate the genetic material or fix errors introduced by genotoxic agents from within or from the environment may alter gene expression and create aberrant protein products. These changes, in turn, cumulatively cause cells to senesce and ultimately die.
It is interesting to note that most of the disorders associated with aging, especially the syndromes of premature aging like Hutchinson-Gilford Progeria Syndrome, Werner's syndrome, and many orders, are linked to defects in the maintenance of this structural integrity of the DNA. It gives credence to the importance of the fidelity of replication and DNA maintenance/repair has on the process of aging.
Furthermore, other chronic illnesses like Diabetes Mellitus, Hypertension, Heart disorders, Cancers, and neurodegenerative disease have been linked to an abnormality in the structural or functional proteins related to genetic aberration from the aging process.
Simply put; therefore, a healthy lifespan in aging is determined by the net result of the limited regenerative replicative ability of cells in the tissues and organs with the rate of accumulation of dysfunctional proteins and dead cells — the regeneration - degenerations ratio.
The scientific or laboratory study of aging, healthspan, and senescence is extremely limited in the human population for obvious reasons of time and ethics. However, research is currently active in various laboratories using model organisms chosen for biological simplicity. More importantly, they can be studied over relatively short periods, like the budding yeast- Saccharomyces cerevisiae and the worm Caenorhabditis elegans, as well as Mice.
These have essential correlations with human DNA and are demonstrated by experimental gene sequencing transcriptional fidelity. Like in humans, they also reveal different genes that facilitate DNA repair, genomic stability, growth factor signaling, and gene silencing, which are fundamental de