Why We Die—Senescence: Part I
Image credits belong to: volfdrag | Pixabay
There are many different ways we can die. You can get hit by an enormous truck, fall from a skyscraper, drink poison, get shot by a gun, etc. Those calamities are the many different ways to speed up what will eventually happen. You cannot just sit alone in a room, untouched by the calamities of the world, and expect to live forever. Death perhaps can be boiled down to one thing.
Senescence and Your Daily Breakdown
Senescence is the progressive breakdown of the body's functions. It happens while you are an embryo in the womb [1]. However, it begins accelerating roughly in your 20s, when your physical strength apexes, and it continues until you draw your final breath. It is likened to growing old, though some may advise that cellular senescence and aging are not exactly synonymous [2].
Cells eventually lose the ability to divide because of DNA damage, thereby diminishing your telomeres (the ends of your chromosomes that prevent them from unraveling or sticking to each other) [3].
Later, I will further discuss telomeres...
Senescence can be conceptualized as your general bodily decline, but it can also be conceptualized as the built-in mechanism against cancer cell proliferation, a mechanism that eventually stops and allows cancer cells to proliferate [3].
When the cellular repair apparatus fails after you live a long life, and cells can no longer return to a pre-damaged state, apoptosis (programmed cell death) is prompted to get rid of the diseased cells endangering their neighbors. But there can be an unrestrained mushrooming of unalterably glitching DNA cells. We call that cancer, and senescence is the final response to that monstrosity. Leonard Hayflick and Paul Moorhead are the two 1960's scientists responsible for starting the concept of senescence. Hayflick was inspired with the concept while extensively beholding human fetal fibroblasts (structural supporters in wound healing and connective tissues) in controlled laboratory conditions. He beheld their continued survival and metabolic activity after they ceased their division [2]. Since then, researchers have become increasingly interested in the omens and causes of senescence and its effects on neighboring cells.
Mitochondrial damage and epigenetics are two causes targeted by senescence research. Epigenetics is concerned with how chromosomal changes impinge on DNA's packaging and how genes are expressed. The existence of senescent cells is a gigantic mystery. Senescent cells are hypothesized to avert cancer by permanently ceasing the cell cycle to allow cancer cells to burgeon. We would expect senescent cells to repair all damage, but that is not always accomplished. Sometimes, senescent cells can switch into an apparently dormant state. However, they are still very metabolically busy by employing senescence-associated secretory phenotypes (SASP) that trigger inflammatory proteins and immune cells to restore tissue architecture and quell the waste accumulated from cellular damage. The inflammatory proteins that are meant to be the good guys in the story can become the bad guys when they mangle neighboring healthy cells because they are left unbridled in their killing. We are at greater risk of Alzheimer's, heart disease, and liver fibrosis as we age because of runaway senescent cells causing unchecked inflammation that leads to immunosuppression. Scientists are interested in potential drugs and therapies to prevent senescent cells' overaccumulation around the body [4].
Image credits belong to: geralt | Pixabay
Senescence that Affects Your Physical Form
Phenotypes, which involve physical form and structure influenced by genetic code and environment, are targets of degenerative change. This is exemplified in the disturbance of normal tissue structures and the senescent cells that attack astrocytes (star-shaped, neuron-protectors in the brain and spinal cord), leading to the progressive damage of neurons and cognition that we find in conditions like Alzheimer's and Parkinson's disease. SASP cells can target chondrocytes (cells responsible for healthy cartilage) and are readily noticeable in joints ailing with osteophytosis (new bone growths in odd places after the body attempts to repair joint damage) and in the breakdown of your vertebrae's shock-absorbers [5] [6].
Whether intended or not, your chromatins (packagers of long DNA molecules into denser structures), your secretomes (proteins ejected into the outer space surrounding the cell), and your tumor-suppressor genes (cell regulators during division and replication) will be impacted by senescence. After Hayflick and Moorhead observed growth dysfunction in human diploid cells, senescence would get tied to telomere attrition (gradual loss of protective caps on chromosomes) and tumorigenesis (formation of tumors). What we know or think we know about cellular senescence is still quite new and rooted in cell culture experiments [7].
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The Loss of Your Chromosome Protection
The gradual loss of your telomeres is called telomere attrition. Though it is often discussed as the cause for aging, it is not the only perpetrator at the crime scene [8].
Telomere attrition impacts your somatic cells (any body cell that is not a sperm or egg cell). Your genome is less protected against nucleolytic degradation (breakage of the nucleotide links in your DNA) when telomere attrition occurs. Wise dietary choices can help to reduce telomere shortening/attrition. Information within the genome relies on telomeres even though bits of telomeric DNA are tossed out the window with every cell division. Senescence and apoptosis are not far behind when your telomeres finally hit their significant limits. Telomere length is like a "biological clock" that tells us about a cell's longevity [9].
Image credits belong to: Clker-Free-Vector-Images | Pixabay
Bladder Cancer, Obesity, and Telomeres
Case-control studies have been performed on the possible links between bladder cancer, telomere attrition, and smoking. Shortened telomeres are often found in carcinomas (cancer of the tissues lining internal organs) [10] [11].
Telomere length could help assess oxidative damage (imbalance of free radicals and antioxidants) caused by smoking and help assess how fast or slow someone is aging. There is a possible antioxidant therapy for this [12].
Telomere attrition could be exacerbated by DNA injury from oxidative stress from obesity based on an examination of 1122 white women aged 18-76. Obese women were found to have shorter telomeres than lean women [13].
This study also mentions the effects of smoking, which I suspect could be accidentally confounded with the effects of obesity. I find it plausible to say that obesity and smoking are both causes for accelerating telomere attrition, inflammation, and white blood cell loss. But if we compare telomere attrition in obese women versus lean women, how do we fully distinguish the extents to which smoking is a cause versus obesity?
Obesity can cut off 8.8 years of your lifespan. Abdomen-based measurements of obesity and your weight-to-height ratio are said to intensely correlate with DNA damage biomarkers, oxidative stress, and raised plasma and urinary levels in unstable oxygen-containing molecules that effortlessly react with other molecules. Obesity coupled with oxidative stress is believed to be connected to uncontrolled adipocytokines (cell-signaling proteins in body fat) [9].
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Pollution and Telomeres
There is concern that pollution is a cause for telomere attrition. Leukocytes (disease-fighting white blood cells) were obtained from office workers and traffic police made vulnerable to toluene and benzene, which are volatile hydrocarbons from coal tar and petroleum. The traffic police were found to have shorter telomeres than the office workers [14].
Telomere attrition and DNA injury have been found among the lymphatic white blood cells of coke-oven workers who were made vulnerable to polycyclic aromatic hydrocarbons [15].
Hypomethylation (cancer-linked event caused by modification of the cytosine base in the DNA sequence) has been invariably associated with telomere attrition in the lymphatic white blood cells of coke-oven workers, which may have a deleterious impact on apoptosis [16].
Image credits belong to: geralt | Pixabay
Stress Hurts Your Telomeres
Telomere attrition has been connected to the glucocorticoid steroid hormones (known to suppress immune responses) that are unleashed during stress. They have been demonstrated to negatively impact antioxidant proteins and worsen oxidative damage and telomere attrition. Oxidative and telomeric damage have been found in the major immunity cells of women who have been made vulnerable to daily stress. Compared to the control group of women not vulnerable to daily stress, the women made vulnerable to daily stress were found to have ten years removed from their lifespans and to be at greater risk of premature age-related problems [16].
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All information in this article is intended for educational/entertainment purposes only. This information should not be used as medical/therapeutic advice. Please seek a doctor/therapist for health advice.
Works cited:
[1] Programmed Cell Senescence during Mammalian Embryonic Development: Cell
[2] Overview of Cellular Senescence and Aging | Cell Signaling Technology
[3] How Does Senescence Relate to Aging Well? (verywellhealth.com)
[4] Overview of Cell Senescence - YouTube
[5] Cellular Senescence: What, Why, and How | Wounds Research
[7] The role of senescent cells in ageing (nih.gov)
[8] Telomere Attrition | Lifespan.io
[9] Telomeres, lifestyle, cancer, and aging (nih.gov)
[10] Telomere length, cigarette smoking, and bladder cancer risk in men and women - PubMed (nih.gov)
[13] Obesity, cigarette smoking, and telomere length in women - PubMed (nih.gov)
[15] https://pubmed.ncbi.nlm.nih.gov/19892797/
[16] Telomeres, lifestyle, cancer, and aging (nih.gov)