Mechanisms of aging and cellular senescence

Mechanisms of Aging

Mechanism of Aging

Aging is a syndrome that occurs as a result of changes that are progressive, deleterious, universal and therefore, irreversible. This aging damage occurs to the cells, molecules that forms the cells, and to the entire organ. The aging process is most commonly associated with old age diseases such as osteoporosis, arthritis, cancer, heart disease and Alzheimer's disease among others; this is because such diseases are associated with degenerative effects experienced by the cells. Scientist have over the years substituted the word "aging" with "senescence" since aging means that when time elapses so does deterioration takes place which is false especially during the early developmental stage Mackenzie, Bussiere and Tinsley ( 21)

Various researches are being conducted to establish the mechanisms of aging, and as part of these research, experiments have been carried out on various living organism so as to shade more light on this concept. These organism include; humans, rodents, flies, worms and hydra. The criteria used to indicate senescence in these living organisms include;

The fruit flies (Drosophila melanogaster ) and the nematode worms (Caenorhabditis elegans ) are the most common invertebrate species used in biological experiments since on reaching maturity both species are composed post-mitotic cells, except for the germ line.

Flies (Drosophila) have been found to have a natural antioxidant enzyme SuperOxide Dismutase (SOD) & CATalase (CAT), but no glutathione peroxidase Comfort

( ADDIN EN.CITE 267; Mackenzie, Bussiere and Tinsley 83)

. This means they are one of the flies in the third category to have both extra genes that support extended lifespan. These transgenic flies have a 73% greater CAT activity, 26% greater SOD activity, and 34% longer lifespan. Unlike the transgenic mice which showed and increased lifespan by about 20% because of its 50 times higher mitochondrial catalase. In flies the gene named age-1 was found to increase its life span by a mean of about 65% and a maximum lifespan of 110% at a temperature of 25°C. As compared to the worms, when they are in their natural habitat (soil), they normally survive at an oxygen concentrations are 1% to 2%, so when the age-1 gene are brought out to a normal atmospheric oxygen concentration of about 21%, they are likely to improve in their longevity.

The flies also have the daf?23 DNA gene, which is in the same family as the daf?2 (DAuer Formation gene) found in worms, responsible for developmental arrest. The daf?2 DNA gene resembles the mammalian gene for the IGF1?1 receptor also known as Insulin-like Growth Factor?1 which is quite similar to insulin receptor Comfort ()

. Dauer gene plays a big role in the flies' larvae stage especially when there is low food availability. As exhibited in the various experiment conducted, dauer has the following characteristics; it is non-reproductive, non-feeding, and resistant to damage from extreme temperature, ionizing radiation, and free-radicals. These properties it exhibits helps it to reduce the aging process Nigam ( 616)

. Experiments have shown that Daf proteins affects fatility and movement of the flies at the same time shifting metabolism towards the breakdown of fats which is similar to mechanism played by insulin in humans.

Another similarity between the genes of worms and that of flies is that they both exhibit gene Sir2 which its activity increases under calorie restriction i.e. reduction of glucose in the cell. Calorie restriction leads to increased NAD+ which activates Sir2 necessary for extending life span.

Rodent cells have a replicative lifespans that is substantially shorter than that of human cells. Experiments done on mice cells have shown that their embryo fibroblasts cease their division after 5-10 PD in culture since mouse embryo fibroblasts are much more sensitive than human fibroblasts to the 20% oxygen in which the cells are cultured, but with reduction of the oxygen to about 3-5%, their replicative lifespan can double Nigam ( 623)

Humans have been found to have a replicative lifespans that range from (10PD to 80PD). For fetal and neonatal, their cells proliferate at a rate of 50-80PD, whereas fibroblast from an adult donor has a replicative lifespan of lower that 40PD. But this replicative lifespan can vary from one donor to the other. In recent experiment on human cells senescence, the fibroblast extracted from various fetal and adult tissue show that they do not differ in any way with the deference in developmental stage, tissue use and the tissue itself Nigam ( 619)

. They all exhibited similar behavior with regard to genetic and environmental control of replicative lifespan. The replicative senescence of the human fibroblasts shows the following characteristics Mackenzie, Bussiere and Tinsley ( 43)