Ageing such a common word with which we all are so accustomed and we use it with day to day life. But do we know about the whole biological pathway the cell goes through to end up in senescence? We are still far away from understanding the biological process of ageing. According to some researchers targeting the ageing process can itself dug up many age-related pathologies. It is a naturally slow process which keeps a check on abnormal growth of cell proliferation. It is a checkpoint which our body needs to maintain a stable growth curve.
The Study of ageing or senescence is called Gerontology (Malder 1998).
What is Senescence or ageing ?
Development does not cease once birth has occurred but continues throughout the lifetime. Ageing or Senescence encompasses all the progressive events of our life that contribute to an increased risk of immunity, disease and death. Ageing or senescence can be defined as a time-related deterioration of the physiological functions necessary for survival and fertility (Gilbert 2010).
“When entropy wins, ageing or senescence sets in”
Senescence has two major facets :
1.The first is simply how long an organism lives (maximum life span)
2. The second concerns the physiological deterioration or senescence that characterizes old age.
According to Gilbert, most people don’t live up to 121 years and most wild mice in the wild do not live to celebrate even their first birthday. The general senescent phenotype is the characteristics of each species. Since biological age is not in accordance with the chronological age it is important to find specific hallmarks and biomarkers that could objectively determine the rate of the age of a person. These biomarkers might be a valuable measure of physiological i.e, biological age. Biomarkers should meet all the criteria.
Biomarkers have few roles like:
Predicting the rate of ageing
Monitoring a basic process that underlies the ageing process
Be able to be tested repeatedly without harming the person
Indicators of biological process, pathological process, pathogenic processes or pharmacological responses to therapeutic intervention.
However, it is believed that the telomere length is a weak biomarker (with poor predictive accuracy), and there is no reliable biomarker that meets all the necessary criteria.
Factors leading to Senescence:
Amongst all the factors leading to ageing here are the few which possibly holds true: oxidative stress, telomere damage/ shortening, DNA damage, Mitochondrial dysfunction, chromatin disruption, inflammation, epigenetic dysregulation and oncogene activation.
Senescent phenotype is known to get activated by various types of stress one of which includes Reactive Oxygenic Species (ROS). Reactive Oxygenic Species are a by-product of the normal oxygen. It is considered that ROS regulate several physiological functions, like signal transduction, gene expression and proliferation. The major cellular sources of ROS are mitochondria, cell membranes and endoplasmic reticulum. While a lengthening of organismal lifespan is associated with low ROS concentration, the senescent phenotype is endangered with high ROS concentrations. If there is an imbalance between oxidant and antioxidant in our body it leads to structural damage to DNA, proteins and lipids and thus becoming one of the factors for ageing.
Telomeres are protein structures of human chromosomes composed of several kilobases(kb) of simple repeats(TTAGGG)n are located at the ends of chromosomes. The length of the telomere is helpful in predicting the replicative ability of the cells. Telomere has the function of protection of chromosome from any degradation arrangements, end to end fusions, and chromosomal loss. Shortening occurs after each cellular division but it is counteracted telomerase enzyme. The length of telomere shortens after each mitosis or oxidative stress or senescence.
Tumour Suppressors And Cell Cycle Inhibitors
The most widely used cell cycle inhibitors and suppressors are p16(cyclin dependant kinase inhibitor 2A, multiple tumour suppresor1),p53,p21,p15,p27.In the process of senescence p53, p21 and p16/retinoblastoma proteins always get activated. Activation is triggered by DNA damage which maybe as a result of telomeric and non-telomeric DNA damage or Oxidative Stress.
HOW SENESCENCE AFFECTS BODY SYSTEM?
EFFECT OF SENESCENCE ON SKIN
As ageing occurs, the skin becomes thinner and less elastic because the number of elastic fibres decreases and collagen fibres undergoes cross-linking. Since there is less adipose tissue present under the subcutaneous layer; therefore old people feel colder.
Homeostatic adjustment to heat is also limited owing to less no. sweat glands. The hair on the scalp tends to thin out. The skin becomes dry because the sebaceous glands become few in number.
PROCESSING AND TRANSPORTING
With old age many organs of our body become inefficient. Our heart reduces in size thus leading to cardiovascular problems and decreased cardiac output. There is an increase in blood pressure because the arteries get filled with plaque(fatty material). The liver gets insufficient blood supply resulting in less metabolism of drugs. Circulatory problems are accompanied by respiratory problems. Due to the growing inelasticity of the lung tissue, there is a problem with ventilation. The kidney also shrinks in size. Salt and water imbalance are commonly observed. Apart from all these problems, there are often reports of loss of teeth, gastritis, ulcers, heartburn.
INTEGRATION AND COORDINATION
Specific disorders like depression, Parkinson disease, Alzheimer disease are seen. These are due to less supply of oxygen in neurons. Hearing Receptors also get stimulated slowly. Glaucoma the build-up of pressure due to increased fluid is more likely to develop because of the reduction of the size of the anterior cavity.
The largest number of study of senescence and ageing processes were made on cell cultures and animal models. Despite new findings at cellular and molecular understandings the ageing process is still limited.
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