Telomeres are an essential part of human cells that affect how our cells age.
Telomeres are distinctive regions of repetitive nucleotide sequences at each end of a chromosome, which protect the ends of the chromosome from deterioration or from fusion with neighboring chromosomes. During DNA replication, the enzymes in charge of this process, because of the way Okazaki fragments are synthesized, are unable to replicate the very ends of the chromosome, so every cell division the ends of the chromosomes are shortened by a certain number of nucleotides, depending on the species and lifestyle of the individual. Telomeres act as disposable buffers, their presence protects the genes before them from suffering the same faith and being truncated.
The telomere sequence in human cells is TTAGGG; it is usually repeated about 3,000 times and can reach up to 15,000 nucleotides in length
Why is there a need for telomeres?
The process of DNA replication doesn`t start from either end of the DNA strand, but rather from the replication start site which can be located anywhere on the DNA strand. This coupled with the fact that all known DNA polymerases read the template strand in the 3' to 5' direction, guaratees the existance of a leading and lagging strand on the DNA molecule being replicated. The flaw of this telomere-requireing process lies in the synthesis of the lagging strand. While the leading strand only requires the presence of one short RNA primer to start replication, the direction of lagging strand sythesis demands for the presence of many RNA primers attached at short distances from where DNA polymerase can then start replication and create so called Okazaki fragments.
Eventually, the last RNA primer attaches, and DNA polymerase, RNA nuclease, and DNA ligase come along to convert the RNA (of the primers) to DNA and to seal the gaps in between the Okazaki fragments. But, for RNA to be converted, it needs to be surrounded by DNA on both sides, which happens at all sites of the lagging strand except the end where the last RNA primer is attached. Ultimately, that RNA is destroyed by enzymes that degrade any RNA left on the DNA, and a section of the telomere is lost.
If telomeres become too short, they have the potential to unfold from their presumed closed structure. The cell may detect this uncapping as DNA damage and then either stop growing, enter cellular old age (senescence), or begin programmed cell self-destruction (apoptosis) depending on the cell's genetic background. Cells dieing-off
or entering senescence results in organ deteriation.
The effects of lifestyle choices on telomere shortening
The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan.
Accelerated telomere shortening is associated with early onset of many age-associated health problems, including coronary heart disease, heart failure, diabetes, increased cancer risk, and osteoporosis
Stress is associated with release of glucocorticoid hormones by the adrenal gland. These hormones have been shown to reduce the levels of antioxidant proteins and may therefore cause increased oxidative damage to DNA and accelerated telomere shortening. Consistently, the women, exposed to stress in their daily life, had evidence of increased oxidative pressure, reduced telomerase activity, and shorter telomeres in peripheral blood cells, relative to the women in the control group. Importantly, the difference in telomere length in these two groups of women was equivalent to 10 years of life, indicating that the women under stress were at a risk for early onset of age-related health problems.
Smoking, exposure to pollution, a lack of physical activity, obesity, stress, and an unhealthy diet increase oxidative burden and the rate of telomere shortening. To preserve telomeres and reduce cancer risk and pace of aging, we may consider including antioxidants, fiber, soy protein and healthy fats in our diet; and staying active, healthy, and stress-free through regular exercise and meditation.
Comments