Classical Evolutionary Theory of Ageing

 

 

 

 

A challenge to define.

   Ageing is a concept that, on the surface at least, seems easy to understand. We think we know what ageing implicitly means however defining it conclusively has proven challenging. Even published reviews have asked simply “what is ageing?” and never managed to plainly define it (Lithgow, 2006). Ageing research is contemporary and multidisciplinary but it is also rife with debate over both theory and even the spelling of “ageing” itself (Martin, 2006). Senescence can be defined as progressive deterioration leading to permanent loss of function over time (Helfand and Inouye, 2002; Helfand and Rogina, 2003) and is sometimes used synonymously with ageing. Ageing also refers to the loss of function as well as the decreasing fertility and increasing mortality with age (Kirkwood and Austad, 2000). Rate of ageing can mean the declining contributions to fitness with time (Williams, et al. 2006). 

 

It should be noted that ageing, senescence and lifespan are interpreted differently (or more problematically interchanged with each other) and this leads to considerable confusion in the literature and arguments over semantics. Biological markers of ageing vary in appropriateness for testing theory and thus resulting experimentation has mainly concentrated on changes in lifespan (Jazwinski, 1998). It is important to note that longevity (age at death) is not necessarily indicative of ageing rate so caution must be exercised with this practice (Lithgow, 2006).  Other potential demographic markers which have been used to describe senescence are survivorship per cohort over time, initial mortality at a certain age, the rate of increase of age-specific mortality, age specific physiological or behavioral changes and finally temporal data concerning reproduction and behavior (Bronikowski and Promislow, 2005).  Biological markers that identify physiological ageing would be extremely valuable for differentiating between rates of ageing such as temporal gene expression and overall longevity (Helfand and Rogina, 2003).

 

 

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Figure 2: (a) Vincent Van Gogh(1853 - 1890 ) painting entitled “An Old Woman From Arles” (b) A painting of the oldest recorded person in history, Jeanne Calment who met Van Gogh in her hometown of Arles, France. She lived until the age of 122 and died in 1997.

 

 

 

Figure 3: A graph representing the gradual decline in survival in wild populations with age and the noticeable difference to individuals who live in protected environments. This result challenges theories on programmed death and suggested that external environmental factors were important (Kirkwood and Austad, 2000).

 

 

 

 

 

Figure 4: It has been proposed that more complex defence such as quills, bird wings, or turtle shells led to increased longevity in those lineages (Partridge and Gems, 2006).

 

 

 

 

 

 If no ageing genes should occur then do long-lived mutants violate the theory of ageing evolution?

  Evolutionary theory at one time predicted that large changes in lifespan could not be caused by single genes but rather the accumulation of many deleterious mutations over time. Recent studies have discovered genes which dramatically affect lifespan when mutated. They are typically involved in the regulation of other pathways but none can cause immortality.   Since the mid-1980’s there have been studies on long-lived mutants of mostly Drosophila and C. elegans and some will be described in detail in this website.

 

                                                  Can we say that ageing evolves?

There is not a straight forward answer and depends mostly on your definition of ageing. Complications arise because ageing is inexorably connected to other biological processes, namely survival, which clearly undergo evolution and can thus suggest that ageing has evolved though perhaps not directly.

 

  Ageing was considered by some to be a paradox because although some genes lead to reduction in reproduction and can undergo evolutionary change, ageing is obviously a maladaptive process (Partridge and Gems, 2006; amongst others). Most now agree that ageing is itself not a program (Lithgow, 2006). The product of ageing is reduced fertility and death which would be selected strongly against in nature if any so-called “ageing genes” arose. This viewpoint suggests that ageing cannot evolve.

 

Prior to the advent of sophisticated genetic research tools, it was hypothesised that ageing was adaptive for the species. August Weismann first suggested that ageing occurred because there was natural selection to remove old versions from a population and free up resources for the young (Partridge and Gems, 2002; Gavrilov and Gavrilova, 2002). He suggested that organismal death was caused by a genetically programmed limit in the amount of somatic cellular divisions. All group selection arguments have come under considerable scrutiny apart from rare exceptions. Natural selection occurs within a single individual and as such is not able to maximize the fitness of the entire species with a process that decreases fitness in the individual itself. Weismann actually changed his opinion on the matter and stated that instead of being deleterious, old variants are merely neutral. Testing the theory of programmed death has resulted in further conformation of its inaccuracies. Unlike predictions, there are radical differences between the longevities of wild versus protected individuals. This is true for both laboratory animals and modern humans who are now able to live to a longer age than ever possible in the wild (see Figures 2&3). This finding is thought to be caused by more benign environments which decrease the fitness cost of having repair mechanisms that can extend life (Gavrilov and Gavrilova, 2002).

 

Longevity and survival must have some genetic component to explain, for example, why monozygotic twins have more similar life spans than dizygotic twins (Kirkwood, 2002). There are also great divergences between the maximum lifespan for various species and even within species. It is often sited that organisms with evolved complex behavioural or structural means of escaping predation, such as flight, tend to have a longer lifespan than their vulnerable ancestors (see Figure 4). However, the accuracy of this type of claim has come into recent speculation and most now agree that life-history traits such as flight affect lifespan in more complex manners (Williams et al, 2006).  A current area of research concerns this change in ageing rate and the accompanying changes in other biological processes (Partridge and Gems, 2006).

 

In a recent paper documenting the so-called truths of ageing, Lithgow stated that:

 1. Genetic programs regulate survival from the cell cycle level to complex hormonal          

pathways.

2. Ageing is not caused by a direct program but is instead the cumulative effect of programs

which control survival, fitness and growth.

3. Life-history evolution has led to the evolution of different life spans (Lithgow, 2006).

 

So although it is relatively clear that survival mechanisms are adaptive and selected in nature based on particular environments, the advent of ageing itself is not programmed because it does not make evolutionary sense (Lithgow, 2006; Partridge and Gems, 2002; amongst others).

 

 

           

 

Why does ageing occur?

   After coming to the conclusion that natural selection cannot select for ageing (the decline in fitness with time) than this is the logical next question. Thankfully this has a somewhat less disputed answer based on two main concepts:

 

1. Since cohort size declines over time due to illness, predation and accidents, in the wild there are few old individuals. This coupled with the fact that reproduction typically decreases with age, means that natural selection does not have as much power to select against deleterious mutations late in life as it could early on. Evolution can only act over multiple generations and mutations that occur post-reproduction are thus irrelevant to natural selection. In wild populations, it is rare for animals to survive to the period of senescence that we associate with humans, domesticated and laboratory animals.  This further suggests that natural selection would not be able to act on genes expressed at old age (Kirkwood, 2002).                            

 

2. The somatic repair mechanisms involved in extending longevity counteract mechanisms increasing fitness early in life (Kirkwood, 2002).  The metabolic resources necessary for survival up to reproduction are more important evolutionarily speaking than genes encoding maintenance and deterioration repair.                                                                                                  

    

   The implications of the first concept of selection decreasing with age formed the basis for the mutation accumulation and the pleiotropy theories of ageing. The second concept is the foundation for the disposable soma theory of ageing.

  

   Even if one argues that because genes are effectively hidden from evolution late in life they therefore cannot undergo natural selection, ageing phenotypes arise from the evolutionary interaction between survival and genes which ultimately affect how and when ageing occurs. It is for this reason that the concept of ageing evolving is still relevant though care should be taken in interpreting any results.  There will always be confusion in terminology and perhaps interpretation because of the multiple layers of complexity that all have a role in determining ageing in different organisms.