Age-related decline in circadian output - Literature review Example

?AGE-RELATED DECLINE IN CIRCADIAN OUTPUT Overview Ageing or the concept of growing old is inevitable for any person who continues to live (Houtenbos et al, 2006). Indeed as long as the process of day and night continues, people will continue to age. Surprisingly, there are research findings that suggest that a lot of people are not so comfortable to notice clear signs of aging in their systems. Reasons why this may be so is varying but one of the commonest and most logical is that a lot of people find aging to be associated with so much psychological, physical and biological challenges. One of these challenges has to do with retarded sleep activity (James, 1999). In most aged people, there is said to be disruptions in sleep and wake cycles. As a way of finding solutions to the problem, researchers have adapted the approach to first knowing what is behind the casue of the problem. One of such researchers whose work is under review is Nakamura et al (2011) How the paper addresses current thinking in its research field Ahead of the study conducted by Nakamura (2011), the existing thinking had been that “a key pattern of rhythmic neural activity begins to decline by middle age (Wolpert, 2011). Essentially and in layman’s language, the existing or current thinking was that as people grow older, there are key factors that have to do with their nervous system that makes it impossible for them to achieve sound and regular sleep as they used to do in their younger days. The rationale affecting the current thinking, which has been backed by research in some cases is that there is physical evidence of sleeping problem in older people as compared to younger people (Inouye and Kawamura, 1979). However, much of the reasons assigned to why this condition was so were based on speculations, most of which assigned psychological and physiological reasons rather than biological reasons. The need for experimentations that could give empirical scientific basis and explanations to the poor sleep in older people was therefore necessary. As part of the current thinking, which concludes that there is a decline in the key pattern of rhythmic neural activity in middle age people (wolpert, 2011), there is a understanding that the key element within the rhythmic neural activity is the brain’s master circadian clock and so if the key pattern of rhythmic neural activity declined, then what was actually being experienced was a decline in the brain’s master circadian clock. It is the latter statement that the experiment of Nakamura et al (2011) addresses directly to measure the output of circadian function my using mice as respondents. As to how the study of Nakamura et al (2011) addresses the current thinking, there are a number of highlighted aspects of the research that can be raised. First, the experiment or study confirms that there is indeed a deficiency of sleep in most ageing people as there are “disruptions in sleep, including decreased amplitude of rhythmic behaviors and fragmentation of the sleep episodes” (Nakamura et al, 2011) in these people. This could be said to be one of the most highlighting point of the study because should their study had disproved the existence of the sleep irregularities, the need for any further studies or research into knowing why the irregularities exists would not have been possible. But directly related to the first issue of discussion raised in their discussion is the realization that the factors behind the deficiency are multivariant and could thus not be attributed to only one factor. Clearly, this is a major difference between the study of Nakamura et al (2011) and current thinking because other neurological biologists like Wolpert who had undertaken similar research were very clear on pointing to the fact that the major causative factor was the decline recorded in the brain’s master circadian clock. This means that Nakamura et al (2011) were more open minded with possible causative factors and thus opened themselves up to testing the authenticity of other propositions behind the cause of the problem (Kawakami et al, 1997). The third and one of the most important findings that comes up for discussion on the study is the fact that the research did not totally denounce the possibility of assigning a decline in the central circadian clock as part of the major causes of sleep defects in older people as the researchers wrote that “an age-related decline in the central circadian clock in the suprachiasmatic nucleus (SCN) may be a key element responsible” (Nakamura et al, 2011). Finally there is a component of the study that took what may be termed as a rather new turn from the current thinking as the researchers made time to have not just a an experimental hypothesis but a controlled hypothesis also by using molecular clockwork in addition to circadian clock. Through the parallel study, the researchers found on one side that in the subparaventricular zone, which happens to be one of the major neural outputs of the SCN of the mice (Hulette et al, 2001), neural activity rhythms were degraded for aged mice, whose age was 13 to 18 months. On the other hand, while expecting that the degraded neural activity rhythms as an entity of the circadian output will be directly reflected in the molecular clockwork, it turned out that “molecular clockwork in the SCN as measured by PER2 exhibited only minor deficits at this same age” (Nakamura et al, 2011). Positive aspects of the Study Reliability of all scientific research papers is very important especially when the scientific research is made up of experimentations (Kolker, 2003) as was in the case of the present paper under study. This notwithstanding, it is not all researchers who have achieved reliability in their research work, mainly because they do not understand the fundamentals of research reliability. Those who understand it also do not see the need to apply it to its logical conclusion. But in the case of the current paper understudy, a major positive aspect of the study was how the researchers put in conscious effort to ensure that reliability was achieved. Commonly, a research is said to be reliable if its findings can be reproduced or generalized given similar or same conditions in another study (Ibrahim, Chain, and Katz, 1995). Generalization of findings is very important but in order to achieve this, researchers ought to have an internal mechanism of testing their results and reexamining their findings. Nakamura et la (2011) did this internal testing and reexamination through the use of two clear hypothetical parameters responsible for decline in sleeping activity in older people (Kang, et al 2006). These two hypothetical parameters were molecular clockwork and circadian clock, which are both components of the neural activity rhythms. With the two, it was possible for the researchers to have their major conclusion that the molecular clockwork really has no effect on the decline in circadian output as “circadian output measured at the level of neural activity rhythms in the SCN is degraded by aging, and this decline occurs before the disruption of key components of the molecular clockwork” (Nakamura et al, 2011). Negative aspects of the experiments The positive aspect of the experiment of ensuring reliability notwithstanding, there is an identified negative aspect of the paper, which has to do with the refusal to correlate the biological aspects of the factors and reasons to any other academic aspects such as psychology or physiology. This is because the study was undertaken amidst a very strong preexisting notion and thinking that the sleeping problems of ageing people was not all about biology and for that matter the central nervous system (Hastings, Reddy and Maywood, 2003). From every indication, should the researchers had incorporated other components and aspects of learning such as psychology and physiology into their biological constituents they would have achieved much significance for their study as the study would have had a wider audience. This is because the implication of the study would have been more applicable. For example people could have been told of specific psychological and physiological activities that aid to the speeding up of the circadian output so that they would have been admonished to stay away from such practices. In the absence of this link, the paper seems to be good only for the biological academicians who would need to apply the findings and conclusions in their further studies. REFERENCE LIST Hastings MH, Reddy AB, Maywood ES 2003, A clockwork web: circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci 4:649–661. Houtenbos, I., Westers, T.M., Hess, C.J., Waisfisz, Q., Ossenkoppele, G.J. & de Loosdrecht, A.A. 2006, Flt-3 internal tandem duplication hampers differentiation of AML blasts towards leukemic dendritic cells. Leukemia, 20, 1892–1895. Hulette, B.C., Rowden, G., Ryan, C.A., Lawson, C.M., Dawes, S.M., Ridder, G.M. & Gerberick, G.F. 2001, Cytokine induction of a human acute myelogenous leukemia cell line KG-1, to a CD1a+ dendritic cell phenotype. Archives of Dermatological Research, 293, 147–158. Ibrahim, M.A., Chain, B.M. & Katz, D.R. 1995, The injured cell: the role of the dendritic cell system as a sentinel receptor pathway. Immunology Today, 16, 181–186. Inouye ST, Kawamura H 1979, Persistence of circadian rhythmicity in a mammalian hypothalamic “island” containing the suprachiasmatic nucleus. Proc Natl Acad Sci U S A 76:5962–5966. James, S.Y., Williams, M.A., Newland, A.C. & Colston, K.W. 1999, Leukemia cell differentiation: cellular and molecular interactions of retinoids and vitamin D. General Pharmacology, 32, 143–154. Kang, H.K., Park, J.S., Kim, S.K., Choi, B.H., Pham, T.N., Zhu, X.W., Cho, D., Nam, J.H., Kim, Y.J., Rhee, J.H., Chung, I.J., Kim, H.J. & Lee, J.J. 2006, Down-regulation of cellular vascular endothelial growth factor levels induces differentiation of leukemic cells to functional leukemic-dendritic cells in acute myeloid leukemia. Leukemia and Lymphoma, 47, 2224–2233. Kawakami F, Okamura H, Tamada Y, Maebayashi Y, Fukui K, Ibata Y 1997, Loss of day-night differences in VIP mRNA levels in the suprachiasmatic nucleus of aged rats. Neurosci Lett 222:99 –102. Kolker DE, Fukuyama H, Huang DS, Takahashi JS, Horton TH, Turek FW 2003, Aging alters circadian and light-induced expression of clock genes in golden hamsters. J Biol Rhythms 18:159 –169. Nakamura et al, Aging Impacts Circadian Output in Mouse SCN. J. Neurosci., July 13, 2011 • 31(28):10201–10205 Wolpert S, 2011. Study shows new evidence of age-related decline in the brain's master circadian clock [Online] http://newsroom.ucla.edu/portal/ucla/new-evidence-of-age-related-decline-210695.aspx Read More