Aging is a common phenomenon that is experienced by all human beings. It is a process where people become older. Moreover, aging is a process that takes place in animals and plants. There is biological explanation of the aging process. In aging, what happens is the decline of body cells. Understandably, there is substantial genetic influence on the aging process and scientists have also established the major factors behind it. This paper examines the existing evidence on genetic influence of the age-related cell decline and the major factors behind it.
Cycle of cell growth and replication
Explanation of the genetic influence on age-related cell decline is often based on the understanding of the cycle of cells growth and replication. The process in which cells grow and replicate is cyclic. It has got two main stages. There is the inter-phase process, where the cell grows and replicates DNA to enable cell division. It is important to understand that cell division is the process in which cells normally replicate and multiply in number (Rodríguez-Rodero, Fernández-Morera, Menéndez-Torre, Calvanese, Fernández & Fraga, 2011). The second phase is referred to as mitosis, where the real division of the cell into two daughter cells takes place. Figure 1 below is a summarized representation of the events, which normally happen during the cyclic process of cell growth and replication. This particular understanding is necessary as the premise for explaining the genetic influence on the age-related decline of cells as well as other factors in it.
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In the above figure, the inter-phase events are indicated by blue arrows. On the other hand, mitosis happenings are demonstrated by the use of brown arrows. Importantly, it is notable from the above figure that there is chance for cells exiting the normal phases into another one denoted by GO. This development could happen on temporary or permanent terms. A case of embryo development has got high frequency of complete cycles because cells are normally actively dividing and growing (Iwasaki & Yamasoba, 2015). However, in adult human beings, where the need for growth and development is low, most cells do remain in the GO phase to perform their specialized work in the human body. In this phase, these cells do not replicate. Examples of such cells include the muscle and nerve ones.
The aging process needs regulation of the cell cycle. In human beings, replication of cells is a process that only has to happen where there is growth and development. It, therefore, means that replication of cells is a process that is relevant in the embryo and young people. In adults, replication is only necessary when there is need for replacement of the worn out or dead cells. The cycle, which leads to this replication, is influenced by factors of growth and proto-oncogenes (Wallace, 1992). Regulation of replication in the adult body is done by anti-oncogenes that produce proteins, which inhibit it. Therefore, interaction between the proto-oncogenes and anti-oncogenes is quite important in adulthood (Tosato, Zamboni, Ferrini & Cesari, 2007). It is also important to note the presence of checkpoints that prevent cell cycle from happening whenever an error occurs.
During aging, the ability of cells to replicate through division dwindles. It means that the wearing out and dying cells are not replaced. This development normally leads to the decline in the strength of tissues and dysfunction of organs. There is existing evidence showing that the interaction between genetic and epigenetic factors influences the age-related decline of cells in human beings. Moreover, there are also other factors of essence in this age-related decline of cells, which include hereditary, stochastic and environmental ones.
The commonly noted event in aging at the cellular level, noted by many researchers, is cell senescence. Cell senescence happens as a result of the exposure to intrinsic as well as extrinsic factors favorable to age-relate decline of cells. Notably, cell senescence features the slow accumulation of DNA damage and epigenetic alterations in the structure of the DNA. These developments usually affect the correct gene expression leading to changed cell function. In this case, the first evidence of genetic influence on age-related cell declined is explained. Vitally, the genotype of a person determines the variation in lifespan (Wallace, 1992). The lifespan of a person as determined by his or her genotype is greatly affected by the tendency of molecular errors accumulation. This accumulation of molecular errors compromises the function of adult stem cell.
Telomeres and the damage of the DNA
One major factor that has influence on the age-related decline of cells is the high increase in incidence of cancer and other chronic diseases. Moreover, progressive tissue degeneration and atrophy originating from the decrease in function of the somatic stem cell is of huge influence on age-related decline of cells. Normally, human cells are in constant exposure to quite harmful conditions in life. This factor causes progressive cell damage that is the basis for aging of the human body.
The most cited and best example of DNA damage as the major cause of age-related cell decline are the progeroid syndromes. They are caused by deficiency in methods needed to occasion DNA repair. Importantly, mutations that take place in some genes usually create huge stress resistance and low rate of damage accumulation hence enhancing long life (Harari & Kupiec, 2017). To show evidence for this statement, researchers cite the mutation within the gene that normally encodes oxidative stress response protein P66shc. This particular protein is the source of prolonged life and protection from different aging diseases in mice (Finch & Tanzi, 1997). It is vital to note that a lot of the existing evidence on the influence of genetic processes on aging is in research works that use mice as the study subject. The same protein also enhances resistance by mice to apoptosis after the oxidative stress.
Telomeres refer to the DNA-protein complexes, which make caps at the ends of linear DNA strands. Their function is stabilization of the strands and prevention of chromosome instability. In the current evidence, there is a correlation established between telomere shortening and the somatic stem cell decline in the course of aging. In this evidence, it is explained that the enzyme telomerase normally adds particular DNA sequence repeats to the ends of chromosomes. These ends are lost through cell division (Johnson, Dong, Vijg & Suh, 2015). This development t restores the telomere length and delays cell senescence, apoptosis and death. However, as age increases, the repetitive DNA at the ends of chromosomes normally becomes short progressively. This phenomenon has been observed in the fibroblasts, lymphocytes and the hematopoietic stem cells. With aging, the telomeres grow seriously short as a result of the repeated mitotic divisions in the absence of enough telomerase enzyme activity. This situation makes cells to be susceptible to apoptosis, mutation and death.
Research works have established crucial connection between telomere shortening and age-related diseases within human beings. This connection is credible evidence that the erosion of telomere and chromosome instability is cause of age-related decline in human beings. Evidence has also been established in the mice, where those that age prematurely have been found to be telomerase-deficient with quite short telomeres (Jose, Bendickova, Kepak, Krenova & Fric, 2017). The adult stem function is normally destroyed by the shortening of telomere. Additionally, researchers have established that the mice that show delayed aging and strong resistance to cancer have string telomerase over-expression with long telomeres. Therefore, there is proof showing the length of telomeres and presence of telomerase enzyme activity as major factors that influence age-related decline of cells in human beings.
Genetic factors influencing aging
In the existing evidence for genetic influence on aging, many factors are implicated by researchers. For instance, studies indicate the huge impact of hereditary factors in genotypes and lifespan variation. It is also important to note that the somatic stem cell function is essential in aging. Therefore, any genetic factor that causes damage to the somatic stem cell function has influence on the aging process in human beings. Mutations in the genomic and mitochondrial DNA result from the low efficiency of repair and do cause dysfunction of the somatic stem cells.
Illustration of the significant influence of the genetic factors in age-related decline of cells is premised on the genes that keep the structure of organisms as well as maintain their proper functioning. The demonstration of the genetic influence on age-related decline of cells is also based on the alleles, which boost the reproductive capacity initially in human life, but do have adverse impacts on later life when they escape natural selective pressure. Another example of genetic influence is explained by the constitutional mutations that are normally phenotypically relevant until late life. During this late life, they escape the natural selection pressure hence cannot be removed from the population.
There are two main classes of lifespan-extension mutants proved to exist in the Caenorhabditis elegans. The first class is that of genes, which have activity in the mitochondrial electron transport chain. An example of genes in this class is the clk-1 . Its mutation normally lowers oxidative phosphorylation capacity moderately and lengthens life in worms. The mutations of this first class have been used by researchers to establish evidence for the link between energy metabolism and longevity. Furthermore, there is the second class of mutants, which has relation to the hormone nature of insulin. An example is the age-1 mutant that extends lifespan in worms, mice and flies. Mice live longer because of improved glucose homeostasis resulting from moderately lowered oxidative phosphorylation. Evidence that lifespan extension can be achieved through an impaired electron transport function was adduced by researchers through studying the mutation of isp-1 , which normally encodes an iron sulfur protein within the mitochondrial complex III. In essence, these findings by researchers through empirical studies of worms, mice and flies serve as credible evidence that reduced mitochondrial function may enhance aging and age-related decline of cells.
It is important to note that evidence of genetic influence on the age-related decline of cells has been adduced using studies on sirtuins. Sirtuins are protein deacetylases. Their function is modulation of pathways mainly implicated in the process of aging. There are specific sirtuins that regulate the amount of glucose in the body and fat metabolism within mammals. This regulation is achieved through enhancement of the mitochondrial biogenesis in the liver and muscles. The enhancement is done through the transcriptional coactivator peroxisome proliferator-activator receptor- γ coactivator 1α (PGC-1α). Sirtuins also do govern cell survival. Cell survival is governed by lowering the p53 tumor suppressor activity (Antebi, 2007). Studies on the yeast plant have proved the work of sirtuins. It has been established that a plant-derived polyphenol known as resveratrol, normally increases the deacetylase activity of certain sirtuins hence elongating lifespan in yeast by 70%. Equally, these results were noted in the short-lived fish species, Nothobranchius furzeri , whose lifespan increased by 60% after being treated with resveratrol. The treatment of fish also led to the maintenance of motor and cognitive capacities. Consistently, the same evidence was established in the middle-aged mice treated by resveratrol and put on high calorie diet. It had longer lifespan. Essentially, these observations strongly indicate that there genetic influence on age-related decline of cells.
Genetic factors and aging
The existing scientific understanding of aging suggests that it is both deterministic and stochastic. It is vital to note that the human senescence is a complex process, which entails both genetic and environmental factors. These genetic and environmental factors normally impact the physiological pathways. Genotype has come out as a major factor determining the lifespan of species. In some cases, diseases like progeroid syndromes have been used to study the influence of genetics on aging process. It is important to note that progeroid syndromes are age-related monogenic hereditary disorders (Finch & Ruvkun, 2001). Therefore, there are genetic factors, which modulate the process of aging. Studies have been done on the populations of centenarians to establish this phenomenon. It is also quite vital to observe that studies on genome-wide case-control association have established several genetic variants connected to age-related cell decline and diseases.
There is sufficient and credible evidence in literature currently, showing the significant genetic influence on age-related cell decline and other factors affecting it. Most of the evidences available are those done on animal species like in mice, worms and the centenarian populations. These subjects have been studied and credible evidence found to link genetic processes to age-related cell decline. Notably, aging is a quite complex process that is all about cell senescence. The existence of variability in terms longevity of lifespan for individuals belonging to the same species clearly shows the influence of genetics on aging. It suggests that aging is influenced by processes, which cause accumulation of errors damaging the repair systems hence compromising the somatic stem cell function.
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