Werner syndrome is one of the best studies progeriod syndromes. It is considered an excellent model for human ageing (Cheng et al, 2007). Patients with Werner syndrome exhibit accelerated ageing and the common phenotypes associated with ageing. In this disease the WRN gene is mutated mainly through chromosomal translocations and this results in the production of a dysfunctional WRN protein (which has multiple roles in DNA metabolism).
McCay et al first provided evidence in 1935 to suggest that caloric restriction slows down the ageing process and that it could potentially increase life span. Research has since expanded and yielded exciting results in many organisms which back up this concept. Bodkin et al (1995) enforced long term caloric restriction on adult male rhesus monkeys. The research group noted that the mortality rate in the control groups was higher than in the dietary restricted group. It can be seen that caloric restriction leads to changes in physiological changes that have the eventual effect of increasing longevity. (Guarente, 2005)
Examinations of model organisms such as mice and other lower organisms has yielded results which suggest that certain genes can contribute to alterations in the rate of ageing (Perls, 2002). The P53 gene is one of these genes. The p53 gene creates a tumour suppressor protein that has many functions. These include its ability to induce cell cycle arrest or activate apoptosis in cells that can’t repair DNA damage or when certain oncogenes are activated. It is commonly referred to as the “guardian of the genome”, due to its ability to prevent genetically unstable cells from entering a cancerous state (Donehower, 2005). In many cases of cancer a mutated p53 gene is present.
When lipids are oxidised by Reactive oxygen species, the resultant products can have a variety of affects on an organism. For example, Malonaldehyde (a lipid oxidation product) is capable of reacting with various molecules (proteins, nucleic acids) and can alter their structural confirmation. This alteration then leads to the immobilization of immune function. Furthermore researchers have found that many sufferers of age related diseases such as liver disease, diabetes and atherosclerosis, have high levels of lipid oxidation products present in cells (Lee, 2004). Frei (1995) also noted that the oxidation of LDLs can lead to the development of cardiovascular disease.
Research has shown that oxidative stress can contribute to human ageing. As we age all of our cells will accumulate oxidation products from lipids sugars, proteins and nucleic acids (Jiang et al, 2006). These oxidation products are known as reactive oxygen species (ROS). These are a group of unstable, highly reactive molecules. They include oxygen ions, free radicals, and peroxides.
Telomeres are structures that cap the ends of chromosomes. They are made up of TTAGGG repeats, these repeats can be up to 20kb long (Britt-Compton et al, 2006). The purpose of telomeres is to act as buffers to protect important segments of DNA from being lost due to the inability of DNA polymerase to replicate all the way to the end of the chromosome. This inability was described by Alexei Olovnikov and James Watson as the “end replication problem” in 1971. Read the rest of this entry »
There are many theories that attempt to provide an explanation as to how we age, because of the huge number of theories I will only to attempt to evaluate the two most prominent genetic theories.
Ageing can be defined as a metabolically active deterioration process which leads to a change in an organism over time. Some of the common characteristics seen with ageing are a decrease in reactions, impaired function, a decrease in reproductive capacity and an overall increase in the chance of mortality. The human life span is determined partially by the rate at which ageing occurs. Over the past decade research into ageing, has yielded results which can help unlock factors that underpin human ageing. Model organisms and premature ageing diseases such as progeria and Werner syndrome have also provided clues as to how the process of ageing occurs (Ruse et al, 2001). There are numerous theories that explain the process of ageing and much research has been done on the topic.
