Updated: Feb 26
The goal of slowing aging has fascinated humankind for millennia but only recently acquired credibility. Recent findings that aging can be delayed in mammals raise the possibility of prolonging human health span.
The desire to live longer and age healthier is one of the essential ambitions of human beings. It is necessary to understand better the intricate molecular processes that evolve in human bodies while they age.
There is a near consensus among aging researchers that it is possible to delay aging by affecting the cellular mechanisms that lead to aging, but only if resources are available to accomplish goals ranging from basic biology to translational medicine.
This blog seeks to give insight into these mechanisms and help to separate facts from the 'junk' floating around the information superhighway.
Here are the fundamentals
Aging, by definition, is said to be a progressive decline in the function of the cellular components of an organism over time that eventually lead to senescence, a progressive decline in the divisive power of cells, and ultimately death.
So aging starts when the sperm fertilizes the egg. The cellular division from then is growth which continues until adolescence; after growth comes repair and renewal as the trajectory of the aging mechanism.
During regeneration and repair, the average human cell can only divide by replicating the 23 pairs of chromosomes made up of double-strand DNA into two copies and daughter cells.
Cells can do this 40-80 times before it 'wears out' depending on which tissue. Notably, Blood cells and epithelial cells of our skin and lining of our gut and internal organs are constantly multiplying because of high 'wear and tear' and hence have the shortest span because of a higher rate of injury and repair.
Overall, Regeneration is supposed to restore tissues to their original state, causing no visible change that maintains organ structural and functional integrity.
However, this is not the reality because the limited capacity of cells to continue to divide beyond a limit mentioned above causes cells to degenerate, go into senescence or die by apoptosis after the limit.
So after a time rate of regeneration may start falling short of the rate of degeneration, leading to structural and functional decline in tissues and organs as aging.
Also, because of continuous zipping and unzipping of the generic material during each cell division, there is a gradual accumulation of 'mistakes' alteration of DNA sequence (known as DNA mutations) and epigenetic changes like aneuploidy (in which a stretch of codes are added to one daughter cell,) during replication process which influences the expression of genes which invariably lead to wrong protein formation and altered function, ultimately leading to cell disease, death or Apoptosis. It is thought that this process shifts the ratio of regeneration vs. degeneration wider.
The DNA damage theory of aging hence postulates that the accumulation of DNA alterations and 'mistakes' during replication result in the loss of functional fidelity of organelles of individual cells.
The damage affects the nuclear genome as well as mitochondrial DNA.
Of note is that the cell has a wide range of repair enzymes known as Polymerases ( DNA polymerase, telomerase) that constantly attempt to repair these damages as they occur, but even those can be overwhelmed.
Therefore, it is the failure to replicate the genetic material efficiently or fix errors introduced by genotoxic agents that invariably alter gene expression and create wrong amino acids sequences and aberrant protein products.
These changes, in turn, cause cells to senesce, age, and ultimately die.
Simplistically, therefore, aging is determined by the net result of the limited regenerative replicative ability of cells in the tissues and organs and the rate of accumulation of dead cells — the regeneration degenerations ratio.
However, this is not the end of the story because of the complex environment of the body and mechanisms that interact to maintain homeostasis; scientists have noted that aging is characterized by a complex and interacting process associated with nine major cellular and molecular hallmarks. They are called the hallmarks of aging.
Aging is the predominant risk factor for most diseases and conditions that limit healthspan. Moreover, interventions that extend lifespan in model organisms often delay or prevent many chronic diseases.
Targeting diseases individually for an aging population is also complicated because most elders have multiple morbidities that interact, confounding therapeutic strategies. By understanding how aging enables pathology, new therapeutics will arise for various chronic diseases, providing an opportunity to extend human healthspan by targeting aging directly.
Twins showing the most significant discrepancies in visible aging signs also had the greatest discordance between personal lifestyle choices and habits.
Adopting healthier lifestyles could result in the postponement of age-associated diseases and the slowing down of the aging process.
Numerous aging genes have been identified in non-vertebrates, which now should be used to develop a systems-level understanding of aging, including both genetic and environmental influences.
Human genome association studies have identified aging-associated gene variations from either genome-wide unbiased or gene-targeted studies, examining orthologs of animal aging genes.
Increasingly, inflammation is linked to aging and chronic disease Acute inflammatory responses to insults such as injury and infection are critical for organismal health and recovery. However, the basal inflammatory response rises with age, leading to low-level chronic inflammation that is likely maladaptive, promoting aging.
There is a need to identify (1) the pathways by which adaptive and chronic inflammation are induced and (2) the outcomes of “inflammaging.” Interventions designed to reduce chronic inflammation while maintaining an effective adaptive response may have broad benefits.
The current approach to treating chronic diseases is inadequate and incomplete. Many damages are done when chronic diseases are diagnosed, and it isn’t easy to undo them. While understanding the unique features of any disease is laudatory and potentially of therapeutic value, approaches to understanding a common cause, aging, will be uniquely important.
If we can understand how aging enables disease, it may be possible (and even easier) to target this common component of the disease. Targeting aging may allow early intervention and damage avoidance, maintaining vigor and activity while offsetting the economic burdens of a burgeoning aging population hampered by multiple chronic diseases.
That is where epigenetics became relevant. The discovery that epigenetic modifications are responsible for the upregulation or downregulation of genes, therefore, brings to the fore the fact that the genes identified for propagating the aging process and causing the manifestation of chronic disorders associated with aging also called 'lifestyle diseases' can be modified.
So as we will consistently find in the blog, understanding these genes led to the specific recommendation of modifiers including lifestyle modifications for the management of these conditions as well as optimizing healthspan by modulating the aging process.
These lifestyle modifications can be achieved through the concepts of MOUTH, MUSCLE, and MIND.