Telomere Indicator of Physiological Age Featured

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Saturday, 12 August 2017 13:06
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Telomere Indicator of Physiological Age Telomere Indicator of Physiological Age
Have you ever wondered, what is your physiological age? Is it more or less than your chronological age? Physiological age determines a person’s health condition. Are we able to determine physiological age? You would think the answer is NO. but it can be done by determining telomere’s length. “Telomere is a repetitive nucleotide sequence (having no meaningful information) at each end of chromosome to protect DNA from deterioration and or from fusion with other chromosomes.” This sequence is about 3000-15000 base pairs in length. In vertebrates this repeated sequence is TTAGGG.
 
Significance of Telomeres
 
Cells divide and increase their number, DNA duplication also occurs. Enzymes involved in this duplication process, can’t continue duplication all the way to the end so some part of DNA is lost and chromosome is shortened. This lost part is some base pairs of telomere. Somatic cells lose about 50-100 nucleotides on each cell division. In this way, telomeres, having no meaningful information, act as CAPS preventing the important information (DNA) from deterioration and preserve the critical information. Telomeres are never tied to each other which allows chromosomes to remain segregate. Without telomeres, chromosomes would fuse with each other. Telomere Shortening Telomeres shorten because of the two major factors:
 
  1. End replication problem in eukaryotes accounts for loss of 20 base pairs per cell division.
  2. Oxidative stress accounts for loss of 50-100 base pairs per cell division.
 
Figure 827.1
 
Oxidative stress in the body depends on lifestyle factors. Smoking, poor diet and stress can cause increase in oxidative stress. With each cell division telomeres shorten, so there are limited number of divisions that a cell can undergo, this limit is called Hayflick Limit. This is to prevent the loss of vital DNA information and to prevent production of abnormal cells. When a cell reaches this limit it undergoes apoptosis that is a programmed cell death. Telomere Lengthening to reverse telomere shortening, there is an enzyme named Telomerase that adds telomere sequence nucleotides and replenish the lost telomere nucleotides. Telomerase activity is not present in all cells. It is almost absent in somatic cells including; lung, liver, kidney cells, adult tissues, cardiac and skeletal muscles etc. In the presence of telomerase enzyme, a cell can divide to unlimited extent without ageing giving rise to tumors. That’s why it is found only in some cells in considerable concentration including germline cells and stem cells. These cells don’t show signs of ageing.
 
Figure 827.3
 
Relation between Telomere’s Shortening and Ageing
 
Figure 827.2It is still controversial that whether telomere shortening is a reason of ageing or is a sign of ageing just like grey hair. Whatever it is, the thing is, it determines your physiological age because ageing cells mean an ageing body. Telomere shortening is related with poor lifestyle. People who are active and have a healthy lifestyle have the same telomere length as someone 10 years younger than them has. Depression causes increase in oxidative stress in the body so the higher the stress, the shorter the telomere is Link between Telomeres and Cancer “Cancer in general is defined as an uncontrollable rapid growth of cells.”
 
What causes these cells to grow uncontrollably?
 
These cells have active telomerase enzyme, which doesn’t let the telomere to shorten, so no Hayflick limit reaches and cell continues to divide. This is the reason why telomerase is not used as an anti-ageing medicine because it has potential to turn normal body cells into cancerous cells. Without telomerase activity cancer cells activity would stop, which is an under research treatment for cancer. However, drugs inhibiting telomerase activity, can interfere with normal functioning of cells that require telomerase. In healthy female breast there is a portion of cells named, luminal progenitors, with critically short telomere length. In these cells telomerase becomes active causing these cells to turn into cancer cells on higher activity. To tackle breast cancer, use of telomerase inhibiting drugs should be practiced. Telomere biology is very important for understanding cancer biology and scientists are working hard on it.
 
 
Reviewed by Dr. Nida Hayat Khan
Editor @ BioScience.pk 

Additional Info

Last modified on Sunday, 13 August 2017 13:21
Tamseel Ch

I'm a student of Microbiology and Molecular Genetics from University of the Punjab. I have insatiable obsession with research in genetics, food and medical microbiology.

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  • NORMAL GASTRIC ANATOMY AND PHYSIOLOGY
    Anatomically, stomach is divided into four parts: cardia, fundus, body, and pyloric part. Cardia is the upper part surrounding the entrance of the esophagus and is lined by the mucus-secreting epithelium. The epithelium of the fundus and the body of the stomach is composed of different cell types including: (i) mucus-secreting cells which protect gastric mucosa from self-digestion by forming an overlying thick layer of mucus, (ii) parietal cells which secrete hydrochloric acid and intrinsic factor, and (iii) peptic cells or chief cells which secrete the proteolytic enzyme pepsinogen. Pyloric part is divided into pyloric antrum and pyloric canal. It is lined by mucus-secreting cells and gastrin-secreting neuroendocrine cells (G cells) (Figure 859.1).
     
    Figure 859.1 Parts of stomach and their lining cells
    Figure 859.1 Parts of stomach and their lining cells 
     
    In the stomach, ingested food is mechanically and chemically broken down to form semi-digested liquid called chyme. Following relaxation of pyloric sphincter, chyme passes into the duodenum.
     
    There are three phases of gastric acid secretion: cephalic, gastric, and intestinal.
     
    • Cephalic or neurogenic phase: This phase is initiated by the sight, smell, taste, or thought of food that causes stimulation of vagal nuclei in the brain. Vagus nerve directly stimulates parietal cells to secrete acid; in addition, it also stimulates antral G cells to secrete gastrin in blood (which is also a potent stimulus for gastric acid secretion) (Figure 859.2). Cephalic phase is abolished by vagotomy.
    • Gastric phase: Entry of swallowed food into the stomach causes gastric distension and induces gastric phase. Distension of antrum and increase in pH due to neutralization of acid by food stimulate antral G cells to secrete gastrin into the circulation. Gastrin, in turn, causes release of hydrochloric acid from parietal cells.
    • Intestinal phase: Entry of digested proteins into the duodenum causes an increase in acid output from the stomach. It is thought that certain hormones and absorbed amino acids stimulate parietal cells to secrete acid.
     
    The secretion from the stomach is called as gastric juice. The chief constituents of the gastric juice are:
     
    • Hydrochloric acid (HCl): This is secreted by the parietal cells of the fundus and the body of the stomach. HCl provides the high acidic pH necessary for activation of pepsinogen to pepsin. Gastric acid secretion is stimulated by histamine, acetylcholine, and gastrin (Figure 859.2). HCl kills most microorganisms entering the stomach and also denatures proteins (breaks hydrogen bonds making polypeptide chains to unfold). Its secretion is inhibited by somatostatin (secreted by D cells in pancreas and by mucosa of intestine), gastric inhibitory peptide (secreted by K cells in duodenum and jejunum), prostaglandin, and secretin (secreted by S cells in duodenum).
    • Pepsin: Pepsin is secreted by chief cells in stomach. Pepsin causes partial digestion of proteins leading to the formation of large polypeptide molecules (optimal function at pH 1.0 to 3.0). Its secretion is enhanced by vagal stimulation.
    • Mucus
    • Intrinsic factor (IF): IF is necessary for absorption of vitamin B12 in the terminal ileum. It is secreted by parietal cells of stomach.
     
    Figure 859.2 Stimulation of gastric acid secretion
    Figure 859.2 Stimulation of gastric acid secretion. Three receptors on parietal cells stimulate acid secretion: histamine (H2) receptor, acetylcholine or cholinergic receptor, and gastrin/CCK-B receptor. Histamine is released by enterochromaffin-like cells in lamina propria. Acetylcholine is released from nerve endings. Gastrin is released from G cells in antrum (in response to amino acids in food, antral distention, and gastrin-releasing peptide). After binding to receptors, H+ is secreted in exchange for K+ by proton pump
  • CONTRAINDICATIONS TO GASTRIC ANALYSIS
    • Gastric intubation for gastric analysis is contraindicated in esophageal stricture or varices, active nasopharyngeal disease, diverticula, malignancy, recent history of severe gastric hemorrhage, hypertension, aortic aneurysm, cardiac arrhythmias, congestive cardiac failure, or non-cooperative patient.
    • Pyloric stenosis: Obstruction of gastric outlet can elevate gastric acid output due to raised gastrin (following antral distension).
    • Pentagastrin stimulation is contraindicated in cases with allergy to pentagastrin, and recent severe gastric hemorrhge due to peptic ulcer disease.
     
    Gastric analysis is not a commonly performed procedure because of following reasons:
     
    • It is an invasive and cumbersome technique that is traumatic and unpleasant for the patient.
    • Information obtained is not diagnostic in itself.
    • Availability of better tests for diagnosis such as endoscopy and radiology (for suspected peptic ulcer or malignancy); serum gastrin estimation (for ZE syndrome); vitamin assays, Schilling test, and antiparietal cell antibodies (for pernicious anemia); and tests for Helicobacter pylori infection (in duodenal or gastric ulcer).
    • Availability of better medical line of treatment that obviates need for surgery in many patients.
  • LABORATORY TESTS FOR GASTRIC ANALYSIS
    1. Hollander’s test (Insulin hypoglycemia test): In the past, this test was used for confirmation of completeness of vagotomy (done for duodenal ulcer).

      Hypoglycemia is a potent stimulus for gastric acid secretion and is mediated by vagus nerve. This response is abolished by vagotomy.

      In this test, after determining BAO, insulin is administered intravenously (0.15-0.2 units/kg) and acid output is estimated every 15 minutes for 2 hours (8 post-stimulation samples). Vagotomy is considered as complete if, after insulin-induced hypoglycemia (blood glucose < 45 mg/dl), no acid output is observed within 45 minutres.

      The test gives reliable results only if blood glucose level falls below 50 mg/dl at some time following insulin injection. It is best carried out after 3-6 months of vagotomy.

      The test is no longer recommended because of the risk associated with hypoglycemia. Myocardial infarction, shock, and death have also been reported.

    2. Fractional test meal: In the past, test meals (e.g. oat meal gruel, alcohol) were administered orally to stimulate gastric secretion and determine MAO or PAO. Currently, parenteral pentagastrin is the gastric stimulant of choice.

    3. Tubeless gastric analysis: This is an indirect and rapid method for determining output of free hydrochloric acid in gastric juice. In this test, a cationexchange resin tagged to a dye (azure A) is orally administered. In the stomach, the dye is displaced from the resin by the free hydrogen ions of the hydrochloric acid. The displaced azure A is absorbed in the small intestine, enters the bloodstream, and is excreted in urine. Urinary concentration of the dye is measured photometrically or by visual comparison with known color standards. The quantity of the dye excreted is proportional to the gastric acid output. However, if kidney or liver function is impaired, false results may be obtained. The test is no longer in use.

    4. Spot check of gastric pH: According to some investigators, spot determination of pH of fasting gastric juice (obtained by nasogastric intubation) can detect the presence of hypochlorhydria (if pH>5.0 in men or >7.0 in women).

    5. Congo red test during esophagogastroduodenoscopy: This test is done to determine the completeness of vagotomy. Congo red dye is sprayed into the stomach during esophagogastroduodenoscopy; if it turns red, it indicates presence of functional parietal cells in stomach with capacity of producing acid.
     
    REFERENCE RANGES
     
    • Volume of gastric juice: 20-100 ml
    • Appearance: Clear
    • pH: 1.5 to 3.5
    • Basal acid output: Up to 5 mEq/hour
    • Peak acid output: 1 to 20 mEq/hour
    • Ratio of basal acid output to peak acid output: <0.20 or < 20%

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