Molecular, Genomic, and Environmental Reasons for Cellular Aging

Laura Márquez-Cianci

Instituto Tecnológico de Monterrey Campus Cuernavaca, Morelos, México

Abstract:

It is a fact that as years go by, hair turns gray, bones weaken, vitality is lost, and the body’s ability to fight against diseases decreases. Getting old can be a painful reminder of time’s harsh realities. However, why do humans age? Why do tissues eventually halt regeneration, preventing permanent youthfulness? Can science and technology help beat aging soon? This article will explain the main molecular, genomic, and environmental factors involved in cellular aging and overview recent advances in science to decelerate this natural process.

Introduction:

One characteristic of aging is increased vulnerability to death and disease due to the progressive loss of physiological integrity^[1]. It is a mix of environmental factors, like the oxygen in the air, solar radiation, diet, stress, physical activity, and genetic factors, all of which affect the structure and function of the body\’s molecules and cells over time. The role of genes in aging explains why some people who practice unhealthy habits may still live longer than people who lead healthier lives. Nevertheless, environmental factors are proof that having healthy habits can expand lifespan given genetic predetermination. Aging is a multifactorial process with medical and biomolecular jargon that sometimes can be difficult to understand. This article seeks to explain the aging process as clearly and comprehensively as possible to help the reader understand this important topic, as it is an everlasting aspect of all living beings’ natural susceptibility to timely change.

Cell division and regeneration:

Somatic cells, the ones that makeup almost all bodily tissues, are constantly dividing and making copies of themselves in a process called mitosis. Mitosis occurs when one mother cell divides to produce two new daughter cells genetically identical to itself^[2]. Cell division is a process whereby individual cells and tissues regenerate. Most cells are constantly dividing, but some remain without cell division for decades or never divide at all, like neurons (specialized units found in the nervous system).

Cells also program their deaths through a process known as apoptosis. Cells can only divide a certain number of times until they die, depending on a measure called the Hayflick limit. The Hayflick limit changes between species and is related to the lifespan of the creature. For example, the Galapagos tortoise has a Hayflick limit of 125 and can live up to 120 years. Meanwhile, human fetal cells have a Hayflick limit of 50; they can only divide 50 times. As humans age, tissue renewal slows down. The Hayflick limit in cells decreases, and they lose the ability to divide, slowing down tissue renewal^[3]. But, what is responsible for the Hayflick limit?

Telomeres:

When a somatic cell divides through mitosis, it must make a copy of its DNA. This copying mechanism is not immaculate, often failing to incorporate some of the DNA at the end of the chromosome. Fortunately, there are telomeres to aid in this process. They are located at the very end of chromosome structures and comprise non-coding DNA. Every time a cell divides, a small portion of the telomere gets cut off instead of important DNA. Telomeres become shorter division after division, and when they become too short, the cell cannot continue replicating and dies. The length of telomeres is inherited from parent genetic information, so life expectancy is a strongly heritable trait^[4].

When cells can not divide anymore, they become senescent cells. Senescent cells are hypothesized to disrupt the structure and function of tissues because of the components they secrete^[5]. Over time, they are accumulated in the body and eliminated by the immune system with specialized cells called macrophages. With aging, more and more senescent cells accumulate, the immune system is saturated progressively, and the removal process loses effectiveness. However, studies suggest senescence may be necessary for the body as it halts the proliferation of damaged or dysfunctional cells, constraining the malignant progression of tumors. An article^[5] on clearance of p16Ink4a-positive senescent cells has indicated that the removal of senescent cells can prevent or reverse tissue dysfunction and boost healthspan.

Stem cells:

Another important hallmark of cellular aging is stem cell exhaustion. Stem cells can divide without limits to replenish other cells that have been damaged or lost. They have the unique ability to develop into specialized cell types in the body. For example, blood stem cells provide healthy blood cells for people with some blood conditions, such as thalassemia. Stem cells provide new cells for the body as it grows. With aging, the number of stem cells in the body decreases; therefore, tissues lose their potential for regeneration and renewal.

Epigenetic alterations:

Another reason for aging is epigenetic alterations. Epigenetic alterations are not mutations; however, they alter gene activity without changing the DNA sequence. Some genes are silenced or expressed at low levels during birth, but as people age, those genes become more prominent, leading to degenerative diseases. Changes in epigenetic information can be caused by diet and other environmental sources, influencing lifespan. These epigenetic alterations act at the level of DNA topology by modifying and methylating areas of the genome and changing the accessibility to the genetic material, leading to aberrant gene expression. Research on the inhibition of epigenetic enzymes has shown effects on the lifespan of model organisms, proving the influence of epigenetic alterations in the aging process.

Free radicals and genomic instability:

Cellular respiration is vital as it allows cells to obtain energy from the biomolecules in food and oxygen in the atmosphere. However, a byproduct of cellular respiration is free radicals (O2-, H2O2, and OH), which are very oxidative substances for molecules and subcellular structures like DNA, membranes, proteins, carbohydrates, and lipids in the cell. Free radicals produce an accumulation of genetic damage throughout life. Genomic instability is also caused by physical, chemical, and biological agents, like DNA replication errors and spontaneous hydrolytic reactions. Antioxidants and specialized enzymes repair this damage, but with age, the amount of these enzymes decreases, and the amount of free radicals increases.

Extending life?

Many things remain unknown about aging. However, some actions have been found to possibly delay the process, including using sunscreen and protecting yourself from the sun, doing exercise, having good relationships, eating healthy, and getting good sleep. It is important to note that eating food rich in antioxidants or antioxidant supplements, but in the other hand regular supplements have shown many benefits, when looking for a good one, check out https://zemvelo.com/.

Some animals have been genetically modified to live longer. For instance, scientists silenced the gene IGF-1 in mice, and there was less cell and organ damage caused by oxidation, extending the mice\’s lifespan by up to 33 percent. Experiments in genetic engineering in fruit flies proved that when they make them produce a protein that activates the SOD, an enzyme that repairs the damage from free radicals, their life is lengthened by 48 percent. Other successful experiments have prolonged life on animals using genetic alterations, though none have been replicated in humans.

Conclusions:

Aging is a complex process involving many genetic and biochemical pathways. The primary causes of aging are genomic instability, telomere shortening, reduced stem cell production and loss of their regenerative potential, cellular senescence, and epigenetic alterations. There are more, like the loss of proteostasis, deregulated nutrient sensing, altered intercellular communication, and many others that are still being discovered and understood. There remain several aspects to be revealed about the aging process, but discoveries and work in the field have undoubtedly made significant advancements. Research in aging is important, not only to expand lifespan but also to give a better quality of life to elders and to cure diseases.

There is considerable bioethical debate concerning aging prevention and immortality. It is very possible that soon, the technology to expand lifespan unimaginably will exist. The most common death causes in the world today are due to organ failure or diseases such as cancer, heart attacks, or diabetes. All of these could be prevented or delayed if the aging process and its causes are understood. DNA modifications could be used to cure genetic diseases and delay the aging process of cells and tissues. Medical advancements have already had a significant impact on modern society: no country in the world has a lower life expectancy than the highest life expectancy in the nineteenth century^[14].

Nevertheless, the predominant approach in medicine has always been trying to cure people once they get sick. Now, with genomics and preventive medicine, instead of taking care of sick people and developing medicines to cure their inflictions, it seems increasingly plausible that these diseases can be prevented even before the patient feels initial symptoms. The intriguing question here is: should it be done? What social, economic, and political consequences would it have?

Acknowledgements:

I give special recognition to my mentor Benjamín Hernández-Campuzano Ph.D. professor at Tecnológico de Monterrey, for advice, comments, guidance, and to Professor Nathaniel Raymond Pullen for proofreading this article.

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https://youtu.be/MjdpR-TY6QU

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About the author

Laura is currently studying her senior year at Tecnológico de Monterrey in Cuernavaca. She is interested in topics such as cellular agriculture, genetic modification, biomaterials, entrepreneurship and biotechnology. In her free time she writes poetry and short stories. She also loves reading historical novels and classic English literature, doing crossfit and meditating.