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Health and Disease

Ageing, genetics and Parkinson’s

Nowadays vast amounts of misinformation surface the internet, constructing controversies. Within the same spectrum, healthcare professionals seek to support or contradict the argument, through evidence-based judgement. Likewise, contributing factors of Parkinson’s disease stand firm ground between the evaluation of healthcare professionals across the platform. The Parkison’s debate, distinctly separates itself into three categories, which will be discussed in this article.

Introduction 

Nowadays vast amounts of misinformation surface the internet, constructing controversies. Within the same spectrum, healthcare professionals seek to support or contradict the argument, through evidence-based judgement. Likewise, contributing factors of Parkinson’s disease stand firm ground between the evaluation of healthcare professionals across the platform. The Parkison’s debate, distinctly separates itself into three categories, enlisted below:

  • Pathological process of PD are exaggerations of those processes involved in ageing (Hindle 156-161)
  • The ageing process makes us vulnerable to diseases such as PD (Hindle 156-161)
  • Pathology of PD is independent of ageing (Hindle 156-161)

Parkison diseases’s pathogenesis combines with complicated interactions between susceptibility factors, and side-effects of ageing, making PD one of the best examples of an age-related disease (Hindle 156-161)

Epidemiology of United Kingdom 

The likelihood of developing Parkinson’s disease increases with age, despite some research indicating Parkinson’s disease developing at any segment of an individual’s life, it has become increasingly common against the elderly population globally. Rationally, Parkinson’s disease is frequently conferred as a degenerative (worsening over the period) and age-related disease. Having said that, correlation between life-expectancy and Parkinson’s prevalence rate varies, between each nation. Taking into account, the United Kingdom, acclaiming one of the highest life-expectancy globally, of 81.65 years  (Macrotrends LLC), prevalence rate was 286.5 per 100,000 person (NICE), whereas throughout age, the prevalence is 4-5 per 100,000 people in people aged 30-39 years, compared with 1696 per 100,000 people aged 80-84 (equivalent to 1.7% of this age group) (NICE). Most studies suggest a mean age of onset in the 70s (Hindle 156-161). 

Interaction Between Neurodegeneration and Aging 

Ageing is simply defined as the process in which the human body’s structure and functions deteriorates over time; recent studies have demonstrated an ageing population contributes to having a significant strain on elderly medicine, especially due to underfunding and limitation of accessibility to resources. Through ageing, the likelihood of developing chronic diseases becomes paramount. When perceived through general perspectives, chronic diseases impose risks of developing other diseases and illnesses, leading to management complications, especially amongst elderly dependents with underlying health risk factors (these health risk factors may be inherited or attributed by their surrounding environment, usually they are classed as non-modifiable and modifiable factors). Despite neurons being susceptible to the combined impacts of ageing, neuronal death is not programmed to occur at a particular time (Hindle 156-161). Cellular and molecular changes of ageing interact with genes and environmental factors to determine which cells age successfully and which succumb to neurodegeneration (Hindle 156-161). However, it is not yet explicit how selective vulnerability diverges, creating various patterns of neurodegeneration in numerous chronic diseases. 

Underlined by the Parliamentary Office of Science and Technology, there are four primary factors contributing towards ageing, detailed below:

  • DNA Mutations (Parliamentary Office of Science and Technology)
    • Mutations occur when the process of mitosis becomes uncontrollable, resulting from excessive exposure to harmful chemicals, or electromagnetic radiation from the environment. Also, a decline in the body’s DNA repair mechanism (Parliamentary Office of Science and Technology), can also influence the rate of ageing.
  • Chromosome shortening
    • Chromosome shortening is caused by the incomplete replication of chromosomes, therefore some chromosomes may be lost or completely damaged as mitosis continues to occur.
  • Age-related deposition
    • Synucleins are small, soluble proteins expressed primarily in neural tissues and in certain tumours (Stefanis 1) which experience age-related decline. When mutations in α-synuclein occur, the protein commences to accumulate abnormally in Parkinson’s disease, Alzeihimer’s disease, and several other neurodegenerative diseases (Stefanis 1).
  • Mis-folded proteins
    • The function of almost every cell in your body, containing a nucleus, depends on the folding of protein. As the process of ageing occurs, the mechanisms responsible for right folding such protein into a particular shape, to form an enzyme-substrate complex, start to decline. Having said, the knock-on-effect becomes toxic to cells and is linked to age-related conditions such as Parkinson’s and cataracts. (Otín et al. 5-6)

Biology Behind Causes of Parkinson’s 

Interestingly, Parkinson’s disease concerns a significant decline of the chemical transmitter: dopamine, in the substantia nigra. The substantia nigra, is a black melanin pigment found within the dopamine cells, hence its name. It has been acknowledged for a long time that there is a frank loss of neurons primarily in this highly localised region, where the dopamine cells are distributed as a thin arching sheet on either side of the brain (Greenfield). However, for any problems with movement, a minimum seventy per-cent of dopamine neurons in the substantia nigra must be lost, consequently the whole population declines. Outlined, the domino-effect is at work, as once a small percent of cells becomes damaged, theoretically the causes complete extinction of the brain region, conferring it as a representation of neurotic death: neurogeneration (Greenfield)

In response, the significant loss of dopaminergic neurons, is immediately increased by the amount of dopamine released from the remaining cells, although direct explanation of the mechanism is not yet confirmed, a possible explanations of how the cells in the substantia nigra would be gradually killed in this way stems from the normal metabolism of dopamine (Greenfield)

Complexity of Diagnosis and Symptoms 

Parkinson’s being a progressive disease further implicates the severity of symptoms developing, for example, slight tremor and shaking of hands may indicate early symptoms of Parkinson’s. Often, diagnosis of Parkinson’s evolves as a misdiagnosis of common changes, experienced due to ageing. Gradual yet continuous tremor can aggregate to developing bradykinesia, alternatively referred impaired or slowed movement; the basal ganglia is responsible for movement and physical functioning. Alongside, it is also dependent on dopamine (produced by dopaminergic neurons) to increase the action of direct pathway between dopamine receptors. As a result, when there is a consistent reduction upon dopamine acting through a direct pathway, it leads to delayed physical responses.

Parkinson’s disease may also impact the sensory system, this consists of problems with hearing, smelling or sight, principally due to a reduction in dopamine, there is a detrimental impact upon the mobility of the visual cortex. The visual cortex is responsible for the normal functioning of the eye, inclusive of blinking, movement of the eyelids and the retina. Furthermore, Parkinson’s disease can deteriorate the individual’s working memory, therefore encoding information from the season to the short-term memory becomes complex, as well as retrieving information from the long-term to the short-term memory. Primarily, due to the fluctuating levels of dopamine the prefrontal cortex, which is responsible for the functioning of the short term memory, becomes impaired.

Conclusion 

Conclusively, the likelihood of developing Parkinson’s disease increases significantly, however there are environmental and genetic factors which contribute towards the diagnosis. Often the mental and abstract impact of Parkinson’s disease is frequently ignored, primarily due to the stigma encountered, especially by elderly dependants who are stereotypically conditioned to develop chronic diseases due to ageing.Consequently, it remains of utmost importance that both health care professionals and society at large continues to establish a positive rapport with elderly dependents, specifically when experiencing loneliness and distress throughout the post and pre-diagnosis process. 

Sheza Dewan, Youth Medical Journal 2022

References:

Greenfield, Susan A. Exploring the Brain. Lecture 13: Parkinson’s Disease. 20 November 1997. Gresham College, Gresham College, https://www.gresham.ac.uk/sites/default/files/20nov97susangreenfield_parkinsonsdisease.pdf. Accessed 19 August 2022.

Hindle, John V. “Ageing, neurodegeneration and Parkinson’s.” Age and Ageing, vol. 39, no. 2, 2010, pp. 156-161. Oxford Academic, https://doi.org/10.1093/ageing/afp223.

Macrotrends LLC. “U.K. Life Expectancy.” Macrotrends, https://www.macrotrends.net/countries/GBR/united-kingdom/life-expectancy. Accessed 19 August 2022.

NICE. “Parkinson’s Diseases: How common is it?” National Institute of Health and Care Excellence, National Institute of Health and Care Excellence, January 2022, https://cks.nice.org.uk/topics/parkinsons-disease/background-information/prevalence/. Accessed 19 August 2022.

Otín, Carlos López, et al. “The Hallmarks of Aging.” Europe PubMED Central, vol. 6, no. 153, 2013. PUBMed, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/pdf/emss-55354.pdf. Accessed 19 August 2022.

Parliamentary Office of Science and Technology. The Ageing Process and Health. no. 571, February 2018. Babraham Institute, Houses of Parliament, https://www.babraham.ac.uk/sites/default/files/media/files/post%20note%20-%20the%20ageing%20process%20and%20health%20-%200571.pdf.Stefanis, Leonidas. “α-Synuclein in Parkinson’s Disease.” Cold Spring Harb Perspect Med, vol. 2, no. 2, 2012, p. 1. National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281589/. Accessed 19 August 2022.

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