How does the elderly chromosome behave? Part-1
Elderly chromosomes activate genes in a very different manner when compared to the genes in young age, and this behavior may affect the immune system, inflammatory or even bone breakdown. Recently a lot of work has been done in this regard by the University of Connecticut. The many changes beneath the surface of the skin are the cause of hair turning grey, wrinkles and many age-related diseases. With recent studies, scientists have found out that our chromosomes also wrinkle with age. Much depends on how our immune system changes and renews it. The chromosomes make the proteins required for life.
The DNA is coiled and curled in the center of every cell in the body. Some parts of the DNA are open and loose whereas some are coiled tightly. In the region which is tightly coiled, it is difficult for the cell machinery to access that portion of the DNA and is therefore unable to activate the genes situated in that part of DNA.
A report published in Journal of Experimental Medicine a research team from UConn Health and the Jackson Laboratory for Genomic Medicine (JAX-GM) has shown that our chromosomes age along with us and some portions of the chromosome curl and close up, making them harder to access DNA that is responsible for defending our bodies against disease. They have found that some genes and pathways are very active in younger people that appear to lose their activity with age and therefore are unable to activate the required genes and in turn to make protein. The open and closed portions of DNA also look very different in young and old beings. The genes are pathways to good health. Recently, immunologist Jacques Banchereau and computational biologist Duygu Ucar have worked on the regions of chromosomes and genes that lose their activity with aging. It is their joint efforts which have brought this study possible.
A human study was done by taking out blood from all age groups to check immune system function. They isolated immune cells from the blood and investigated how the immune cells’ activate genes and how they get changed with age. It was found that the regions of chromosomes that are coding for genes which are responsible for the development and differentiation of T-cells that help us in defending against flu, viral infections and some of the cancers get closed in the elderly. These are found to be open to young people. Similarly, the regions of a chromosome which code for genes associated with cell death and inflammation seem to be more open in the elderly.
There is a specific role of disease-causing genes and genetic factors for the cause of dementia. The most common being Alzheimer’s disease. Most age-related neurodegenerative disorders come under proteinopathy where specific proteins abnormally accumulate and get deposited in the brain. The complications can be like amyloidopathies, tauopathies, synucleinopathies, TDP43-opathies, prionopathies, and polyglutaminopathies. Polyglutaminopathy is strictly hereditary.
However, the others are caused by dominant-acting disease gene mutations. They could also be nonhereditary caused by many factors and even advancing age. Physical activity determines Huntington’s disease and other polyglutamine diseases. Alzheimer disease’s (AD) falls in between genes/environment factors. The mutations in specific genes, deposits of α-synuclein in Lewy bodies accompanied with amyloid plaques where they interact with the amyloid/tau pathways in the central nervous system (CNS).
Most of the times the age of 65 years is the dividing threshold. Scientists have identified three disease-causing genes and the Apo E risk factor which has led to a much reliable conclusion of critical pathogenic events in the AD. Symptomatic therapies exist for the AD, but there are no preventive therapies. A link between MS4A2 and AD has suggested the role of pathogenic neuro-inflammation in the pathology of the AD. The MS4A genes are present on chromosome 11 in humans.
Several of the late-onset AD genes (ApoE, CLU, CR1, CD33, ABCA7, and MS4A) associated in some way in the regulation of inflammatory mechanisms. This supports the significant role of the immune system and neuroinflammation in AD pathogenesis. Sialic acid is a binding immunoglobulin which acts as lectins. CD33 belongs to this category which regulates the functions of the cells in innate and adaptive immune systems. Recent studies have shown that dimers or slightly larger oligomers are the keys for toxicity.
To be contd……….