Why do we Age?

Early theories on this subject (Medawar, 1952, Haldane, 1941) tried to understand how something as negative as ageing could have been positively selected for in evolution, especially since most animals in the wild do not live to old age. Only captive animals that are protected from predation, starvation or physical trauma, live to and die from old age. To give an explanation for this problem, Medawar hypothesised that there is a declining force of natural selection with age. Harmful genetic events that are expressed prior to sexual maturity of an individual will be strongly selected against, whereas the expression of such changes at later stages will not be subject to such negative selection. Later, the term antagonistic pleiotropy was contributed to the topic of evolutionary ageing (Williams, 1957). Antagonistic pleiotropy refines the ideas set by Medawar by suggesting that late-acting deleterious genes may be favoured by selection and be actively accumulated in individuals if they have beneficial effects early in life. Such beneficial effects may include the enhancement of an individual’s ability to survive until the reproductive period and/or to carry out reproductive activities in a successful manner.

Another explanation for the conflict between reproduction and longevity came much later with the Disposable Soma theory (Kirkwood, 1977). Unlike the antagonistic pleiotropy theory, the Disposable Soma theory does not explicitly implicate genes as being involved in the ageing process. It instead focuses on the distribution of precious metabolic resources for either increasing reproductive capacity or somatic cell maintenance (DNA repair, protein turnover and antioxidant defences etc). Therefore, organisms have evolved in such a way that the amount of energy invested in maintaining the somatic tissue is sufficient to keep the individual alive long enough to reproduce, but less than what is required to keep it alive indefinitely.

Definition of normal Ageing

Ageing, the process of growing old, is defined as the gradual biological impairment of normal function, probably as a result of changes made to cells (mitotic cells, such as fibroblasts and post-mitotic cells, such as neurons) and structural components (such as bone and muscle). These changes would consequently have a direct impact on the functional ability of organs (such as the heart, kidney and lungs), biological systems (such as the nervous, digestive and reproductive system) and ultimately the organism as a whole.

The following is a description setting out five criteria’s for ageing, as proposed by Strehler (1962).

Cumulative: Effects of ageing increase with time.
Universal: All members of a species display signs of ageing.
Progressive: Ageing is a series of gradual changes.
Intrinsic: Changes would take place even in a “perfect” environment.
Deleterious: Changes which occur compromise normal biological functions.

Like ageing, disease is also defined as an impairment of normal function within a living organism. Since the ageing process leads to biological impairment, it would not therefore be a surprise if some of these age-associated changes manifest themselves as disease. Evidence providing a link between ageing mechanisms and age-related disease development/progression is gradually increasing (discussed at a later date).

Problem of Ageing

Increasing life expectancy is a positive development, but is not without its own problems. The prevention or elimination of causes of death in early life has resulted in a population consisting of an increasing proportion of elderly people. The United Nations populations division estimated that the number of persons aged 60 years and older in 1999 was nearly 600 million worldwide and was projected to reach about 2 billion by 2050 (UN,1999). This means that by the year 2050, the population of older people will be larger than the population of children for the first time in history. In the UK alone it has been estimated that the number of people over the age of 65 is expected to rise by 81 percent over the next five decades (Government Actuary’s Department; www.gad.gov.uk).

The ageing process is associated with an increasing rate of morbidity, the period of time spent sick before recovery or death. Thus, since the elderly population is increasing, more and more people are going to require care. Therefore, to keep pace with demographic change, the number of places taken in residential care homes, nursing homes and hospitals would have to rise. More money is going to be required to keep up with the needs of a changing population, especially in healthcare. It has been estimated that total UK spending on long-term care would rise from £12.9 billion in 2000 to around £53.9 billion by 2051 (London School of Economics; www.lse.ac.uk).

Improvements in general health or advances in treatment of disabling illnesses could lead to a reduction in the proportion of older people needing residential and nursing home care. In order to develop new treatments and management strategies to help deal with the consequences of an elderly population, a clear in-depth understanding of the molecular mechanisms which contribute to the human ageing process and the development of age-related diseases is thus required.

Introduction

During the latter half of the 20th century the average life expectancy throughout the developed world began to increase rapidly. The term “life expectancy” is often confused with “lifespan”, which measures a subtly different parameter. Life expectancy represents the likelihood of surviving to a given age and is often an indicator of the overall health of a country. Increases in life expectancy in developed countries are mainly due to improvements in medicine, public health and nutrition. The primary cause of death in such countries is age-related diseases such as, cardiovascular disease, strokes, infection as result of impaired immune function and numerous cancers. Conversely, life expectancy can fall due to problems such as famine, war, disease and poor health. For example, in regions of Africa and Asia where AIDS is a predominant cause of death, life expectancy is dramatically decreased compared to developed countries and is expected to decrease further if medical intervention is not effective (Logie, 1999). The average life expectancy of a person living in a developed country is about 75 years compared with that of 43 years in some regions of Africa. Lifespan on the other hand is the maximum survival potential as defined by the longest surviving member of a population. For humans, it has been estimated to be between 115 and 120 years. Increases in life expectancy have not resulted in any significant increase in the maximum human lifespan.