was the result of cumulative insults to the body ® the Ôwear and tearÕ hypothesis. Today, theories of ageing fall into three main categories: genetic cellular mechanisms; non-genetic cellular mechanisms; and physiological mechanisms.
Genetic cellular mechanisms Theories based on genetic cellular mechanisms are predicated on the idea that the lifespan of an organism is genetically determined. There is much evidence to support this point of view; for example, the offspring of long-lived parents tend to have a longer than average lifespan as well. Pre-programmed longevity would also explain why human cells grown in culture will only divide a certain number of times (the Hayflick limit), and why cells derived from older donors have a lower limit compared with cells from younger individuals. One variant of this theory supposes
that damage to DNA over the course of a lifespan is responsible for ageing. The body has endogenous DNA repair mechanisms, so it is not entirely clear how this DNA damage could accumulate. Certainly, the rate of mutation in normal DNA is too low to account for the phenomenon, although a breakdown in
the repair mechanism itself, or errors in the DNA replication process, might account for it.
Non-genetic cellular mechanisms Non-genetic cellular models echo the theories of Bacon. They hold that ageing is the result of progressive cell damage caused by environmental factors, such as exposure to ultraviolet light, or the accumulation of harmful substances in the body, rather than being innate. There are a number of variants of this hypothesis: that ageing is the result of abnormal cross-linking of macromolecules such as nucleic acids and proteins, for example. It is known that the development of wrinkles in old age is associated with increased cross-linking of collagen molecules in the skin. Also, it may be that these changes occur at a time when the immune system is less able to deal with abnormal proteins. Another variant of this theory holds
that the accumulation of free radicals in the body directly damages DNA ® the use of antioxidants to fend off the signs of ageing is directly related to this hypothesis.
Physiological mechanisms Physiological explanations of ageing are all based on the idea of a gradual
PETER CHARLISH Principal Analyst, Informa Business Information
email:
peter.charlish@informa. com
Spanish researchers have shown that gene therapy to increase levels
of the enzyme telomerase allows older mice to live not only longer, but also healthier lives.
prime-journal.com | July/August 2012 ❚ 59
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