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2.1: Theories of Aging

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    In the past, maximum life span (the maximum biological limit of life in an ideal environment) was not thought to be subject to change with the process of aging considered non-adaptive, and subject to genetic traits. In the early 1900’s, a series of flawed experiments by researcher Alexis Carrel demonstrated that in an optimal environment, cells of higher organisms (chickens) were able to divide continually, leading people to believe our cells to potentially possess immortal properties. In the 1960’s Leonard Hayflick disproved this theory by identifying a maximal number of divisions a human cell could undergo in culture (known as the Hayflick limit), which set our maximal life span at around 115 years. Life span is the key to the intrinsic biological causes of aging, as these factors ensure an individual’s survival to a certain point until biological ageing eventually causes death.

    There are many theories about the mechanisms of age related changes. No one theory is sufficiently able to explain the process of aging, and they often contradict one another. All valid theories of aging must meet three broad criteria:

    1. The aging changes that the theory addresses must occur commonly in all members of a humans.
    2. The process must be progressive with time. That is, the changes that result from the proposed process must become more obvious as the person grows older.
    3. The process must produce changes that cause organ dysfunctions and that ultimately cause a particular body organ or system to fail.

    Modern biological theories of aging in humans currently fall into two main categories: programmed and damage or error theories. The programmed theories imply that aging follows a biological timetable (regulated by changes in gene expression that affect the systems responsible for maintenance, repair and defense responses), and the damage or error theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of ageing[1].

    These two categories of theory[2] are also referred to as non-programmed aging theories based on evolutionary concepts (where aging is considered the result of an organism’s inability to better combat natural deteriorative processes), and programmed ageing theories (which consider aging to ultimately be the result of a biological mechanism or program that purposely causes or allows deterioration and death in order to obtain a direct evolutionary benefit achieved by limiting lifespan beyond a species-specific optimum lifespan (Figure 1).

    The programmed theory:

    1. Aging by Program, where biological clocks act through hormones to control the pace of aging.
    2. Gene Theory, which considers aging to be the result of a sequential switching on and off of certain genes, with senescence being defined as the time when age-associated deficits are manifested.
    3. Autoimmune Theory, which states that the immune system is programmed to decline over time, leading to an increased vulnerability to infectious disease and thus ageing and death.

    The damage or error theory:

    1. Wear and tear theory, where vital parts in our cells and tissues wear out resulting in ageing.
    2. Rate of living theory, that supports the theory that the greater an organism’s rate of oxygen basal, metabolism, the shorter its life span
    3. Cross-linkage theory, according to which an accumulation of cross-linked proteins damages cells and tissues, slowing down bodily processes and thus result in ageing.
    4. Free radicals theory, which proposes that superoxide and other free radicals cause damage to the macromolecular components of the cell, giving rise to accumulated damage causing cells, and eventually organs, to stop functioning.

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