Biological Theories/Models of Ageing

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Biological Theories/Models of Ageing

Biological theories of ageing focus on the physiological changes that occur in individuals as they age. Biological ageing is usually considered to begin after the third decade – these decrements are almost always ‘obscure’ until the person is placed under a certain volume of physiological stress (environmental, disease, exercise or metabolic stresses)  unable to respond as effectively as when younger person  becomes progressively more difficult to compensate for these stresses. It is this inability to respond to stress, regenerate following illness and overall degeneration in function that eventually results in death.

This ageing process is extremely complicated and exact mechanism is not known, with the distinction between aging and disease being blurry. The ageing process is complicated by changes that occur due to the presences of disease.

Timiras (1994) makes the following distinctions between ageing and disease:
• ageing is a universal process, shared by all living organisms, whereas disease is a selective process, varying with species, tissue, organ, cell, and molecule
• ageing is intrinsic, dependent on genetic factors, whereas disease is intrinsic and extrinsic, dependent on both genetic and environmental factors
• ageing is always progressive, whereas disease may be discontinuous and may progress, regress, or be arrested entirely
• ageing is always deleterious and likely to reduce functional competence, whereas disease is occasionally deleterious, often causing damage that is reversible
• ageing is irreversible, whereas disease may be treatable and often have a known cause

Several hundred theories exist in an attempt to explain the ageing process, but none of them are adequate to explain all aspects and none have gained universal acceptance. Each theory can explain at least some of the biological changes that occur with aging. Some theories have been more persuasive than other at different times.

Molecular Theories

Protein error theory/error catastrophe theory:
Error theory  continual replication of cells  accumulation of protein errors or altered proteins due to a gradual decline in precision of DNA transcription and RNA translation. As proteins play central role in structure and function  alterations in normal physiological functions  cells (and body) unable to respond to stresses or function at optimal levels.

Somatic mutation theory/stochastic model:
Accumulation of errors/damage in DNA due to exposure to radiation or chemicals over a lifetime  interferes with cellular function. The structure of the genetic code is changed  change in amino acid sequence of proteins and enzymes. This theory is consistent with the increased incidence of cancers with age.

Ageing program theory/finite cell division theory/gene regulation theory/Hayflick limit theory:
Cells may contain an ‘ageing’ or ‘senescence’ gene that function as a biological timekeeper  the cell is programmed for only a certain number of cell divisions – called the Hayflick Phenomenon showed that fibroblasts undergo approximately 50 doublings before replication ceases). This assumes that life expectancy is pre-programmed, as the deterioration in cells was not dependant on environmental influences.

System Level Theories

Overuse theory/wear and tear theory:
The body just ‘wears out’ due to mechanical stress – this equates the body with the ‘wear and tear’ of a machine. Ageing is considered inevitable as cell and body structures gradually wear out. While cells and body tissues have repair mechanisms (machines don’t), so damage to the cell is assumed to occur when this capacity is overcome. Under this theory cells with a higher metabolic rate might wear out earlier (rate of living theory).

Neuroedocrine theory:
As the function of the neuroendocrine system controls most of bodies functions (especially the hypothalamus/pituitary system) decline with age  drop in physiological process of most of body’s physiological functions. It is postulated that a biological clock acts through the hormones. Melatonin is believed to play a role. Testosterone replacement has been shown to reverse or halt some of the declines associated with ageing in those who are hypogonadal – but benefit/risk of use is not known. However, not all of the changes seen in ageing can be explained by a decline in hormone function.

Immunological theory:
This theory assumes that the immune system is the biological clock or pacemaker of the ageing process.
Two aspects to this theory:
1) Immune system less able to regulate body’s immunity  subclinical infections  ageing
2) With age, loose ability to distinguish self from non-self  increasing number of autoimmune reactions  reduction in efficiency of many organs and physiological functions  more infections, disease and cancers.

Cellular Theories

Free radical theory:
Free radicals are natural by-products of metabolism – they are atoms or molecules that contain an unpaired electron  highly reactive  randomly react with other structures  damage protein (especially cell membranes), enzymes and DNA  cells become less able to function under stress  unable to efficiently function and replicate genetic material  global decline of body to cope with stresses. Mitochondria are a major site for the generation of the reactive oxygen radicals (due to reaction that generates ATP) and are a major site of damage. It is speculated that damage to the mitochondrial DNA could be an important cause of ageing, as this would affect the energy generation by the cell from the damage to ATP synthesis. It may be possible to mediate some of the effects of ageing by the use of antioxidants.

Cross-linkage theory:
Cross-links form to stabilise macromolecules in cells – it is assumed that this process is enhanced with ageing  stronger chemical bonds formed  increasingly brittle tissues and interferes with DNA and RNA replication and normal metabolism  accumulation of waste products. Collagen is the most abundant protein in the body – it becomes increasingly cross linked with age  collagen becomes less soluble and more rigid. Free radicals, glycation (glycosylation theory) and UV light all increase the cross-linking of collagen.

Waste product accumulation theory:
Progressive accumulation of ineffective biological materials in cell  interferes with normal functioning  damage accumulate with time. Lipofuscin (‘age pigment’) is the most studied waste product that accumulates in cells (formed by cross linking of lipids and protein) – it appears not to be toxic, but its accumulation takes up space in cell  cell functions less efficiently.

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