What Causes The Cells To Age Biology Essay

Published:

This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.

Aging is regarded as an endogenous, progressive, irreversible and deleterious process which results the functional capacity of cells and tissues to decline gradually. (Buffenstein, et al., 2008). Although hair graying and gradual loss of skin colour represent the most common phenotype of human aging, one classical hypothesis that may explain this phenotype is known as "free radical theory of aging" proposed by Denham Harman. (Osawa, 2009). He postulated that the fundamental cause of aging is due to the harmful actions of reactive oxygen species (ROS) which are endogenously formed during normal metabolic process that damaged the cells. (Buffenstein, et al., 2008).

The loss of hair and skin colour is due to the reduction of melanocytes. Melanocytes are specialised cells that are present in the basal layer of the epidermis. They are responsible for the generation of pigmented skin, hair and eye and protect the skin from genotoxic stress of ultraviolet radiation. Melanocytes synthesize melanin pigment within melanosomes are transferred to keratinocytes and accumulate to produce pigmented skin and hair. However, free radicals produced via melanin biosynthesis reactions induce oxidation stress and subsequent cytotoxic elimination of melanocytes, leading to gradual loss of skin and hair colour. (Osawa, 2009).

ROS are produced as inevitable by- products during aerobic metabolism at the electron transport chain (ETC) in the mitochondria. The function of mitochondria is to provide cellular ATP under aerobic condition. Complex I and Complex III of the ETC are the main sites of ROS production. (Greer, Pine, Busbee, 2005). More than 95% of oxygen is fully reduced to water and less than 5% of the oxygen is reduced to ROS during oxidative phosphorylation in the mitochondria. (Reiter, 1997).

ROS is regulated at a low concentration and they help to maintain homeostasis in the normal healthy tissue and regulate mitogen- activated protein kinase pathways. ROS are also second messengers that activate NF- kappa β which controls DNA transcription via tumour necrosis factors and interleukin- 1. However, if ROS level is uncontrolled, they can cause extensive damage on macromolecules. (Buffenstein, et al., 2008).

The three types of ROS are superoxide anion radical, hydrogen peroxide (H2O2) and hyroxyl radical. A free radical is a molecule that possess unpaired electrons which is highly reactive and destructive. (Reiter, 1997). The hydroxyl radical is produced from H2O2 and superoxide anion either by exposure to ultraviolet light or by interaction with transition metal ions such as iron which initiate macromolecule oxidation. (Greer, Pine, Busbee, 2005). Superoxide anion radical is formed due to the electron leakage from the intermediate electron carrier to oxygen. Due to their unpaired electron, superoxide anion radical and hyroxyl radical are known as free radicals. H2O2 and its radical derivatives and hydroxyl radical are the most destructive on the mitochondrial membranes. (Reiter, 1997).

Firstly, high level of ROS will cause disturbance in the cellular pro- oxidant and antioxidant balance which induces oxidative stress. The generation of pro- oxidants are in form of ROS, including superoxide and hydroxyl radicals. (Greer, Pine, Busbee, 2005). Damaged pro- oxidant shift may be the consequences of either an antioxidant defense deficiency or enhanced pro- oxidant environment due to overabundance of external adverse stimuli. Henceforth, these may imbalance the pro- oxidant and antioxidant ratio, favoring oxidative stress which damage tissue, DNA and membrane. (Iriti and Faoro, 2008). Aging is usually associated with increasing level of oxidation as ROS level increased due to the mitochondria function declines and decreased in endogenous antioxidant defenses. (Allen, 1998).

Secondly, if ROS level is uncontrolled and they are not completely neutralised by antioxidants, high levels of ROS will inflict irreversible oxidative damage on biological macromolecules within cell. For instance, ROS can cause proteins to lose their sulfydral groups or undergoes carbonylation and inactivate enzymes or subject them to proteolysis. In addition, ROS can peroxidate the polysaturated fatty acids of membrane, terminating their function. Moreover, it causes oxidative damage on DNA such as alteration of base pairs, strand breaks and DNA- protein crosslink. (Luckinbill and Foley, 2000). Free radicals react with nucleic acid will develop mutation, influences cell cycle and apoptosis. (Anson and Bohr, 2000)..

An example of DNA oxidation product is 8- oxo-7- hydro-2'- deoxyguanosine (8-oxo-dG). 8-oxo-dG is a mutagenic DNA lesion which mispair with adenine during DNA replication and transcription so that DNA polymerase will fail to recognise the mismatch. Hence, the template strand results in a G- A mismatch and it is unrepaired. Damaged mitochodrial DNA (mtDNA) is caused by deletion and oxidatively induced lesion 8-oxo-dG. mtDNA deletions were found to accumulate with age while increased level of 8-oxo-dG is seen with increase in age. As mtDNA is closely associated with mitochondrial ETC, thus, when these mtDNA mutation accumulate, it will alter the function of ETC and increase in ROS production. (Anson and Bohr, 2000).

Lastly, antioxidant system is induced in the presence of ROS in order to defend against ROS production and eliminate them. The antioxidant system is comprised of antioxidant enzymes such as catalase, copper- zinc superoxide dismutase (Cu/ Zn SOD), manganese superoxide dismutase (Mn SOD) and glutathione peroxidase and non- enzymatic antioxidants like vitamins, glutathione and uric acid. Intracellular antioxidants are either synthesised or transported into cell and scavenge the oxidant radicals during oxidative phosphorylation. (Luckinbill and Foley, 2000). SOD is responsible for dismutation of superoxide to H2O2 and catalase catalyse removal of H2O2. The non- enzymatic antioxidants protect the cells from toxic oxidation reaction. Overall, this prevents damage to cells and tissues, especially the mitochodria membrane. However, some ROS do escape the scavenging system and inflict oxidative damage to macromolecules. (Allen, 1998).

In conclusion, aging is caused by gradual accumulation of oxidative damaged macromolecules throughout a lifetime. These ROS may increase in damaged or aged mitochondria and continue to accumulate beyond physiological levels if they are not repaired. This will eventually lead to physiological deterioration and phenotypic changes in human such as aging and age- related disease. (Buffenstein, et al., 2008).

Writing Services

Essay Writing
Service

Find out how the very best essay writing service can help you accomplish more and achieve higher marks today.

Assignment Writing Service

From complicated assignments to tricky tasks, our experts can tackle virtually any question thrown at them.

Dissertation Writing Service

A dissertation (also known as a thesis or research project) is probably the most important piece of work for any student! From full dissertations to individual chapters, we’re on hand to support you.

Coursework Writing Service

Our expert qualified writers can help you get your coursework right first time, every time.

Dissertation Proposal Service

The first step to completing a dissertation is to create a proposal that talks about what you wish to do. Our experts can design suitable methodologies - perfect to help you get started with a dissertation.

Report Writing
Service

Reports for any audience. Perfectly structured, professionally written, and tailored to suit your exact requirements.

Essay Skeleton Answer Service

If you’re just looking for some help to get started on an essay, our outline service provides you with a perfect essay plan.

Marking & Proofreading Service

Not sure if your work is hitting the mark? Struggling to get feedback from your lecturer? Our premium marking service was created just for you - get the feedback you deserve now.

Exam Revision
Service

Exams can be one of the most stressful experiences you’ll ever have! Revision is key, and we’re here to help. With custom created revision notes and exam answers, you’ll never feel underprepared again.