Redox Metabolism and Longevity Relationships in Animals and Plants

Vol 62

Christine Foyer, Richard Faragher, Paul Thornalley

• Publisher: Taylor & Francis
• Year: 2009
• Print ISBN:
  9780415419543
• eBook ISBN:
  9781135238926
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

Redox Metabolism and Longevity Relationships in Animals and Plants focuses on the recent issues that have emerged in ageing research in both the animal and plant kingdoms. This volume reviews current concepts concerning cellular redox homeostatis and ageing in animals and plants, relationships to programmed cell death, the production of oxidants and dicarbonyls, the ways that different organisms perceive and respond to oxidative, nitration and glycation challenges, and how this might be intricately connected to ageing and lifespan.

1
What can we learn from the cross-species biology of ageing?

Richard G.A. Faragher

1 Introduction: What is ageing and why should we care?

In 1967, the Society for Experimental Biology played host to a symposium on the biology of ageing which included studies of the comparative biology of ageing in plants, insects, protozoa and mammals (Woolhouse et al., 1967). Scientists lacking an all-consuming interest in the field were less than impressed. One participant in particular was heard to remark that ‘a professional biochemical team could have all this sorted out in a fortnight’ (Woolhouse et al., 1967). Four decades on, this chapter is written with much the same intent as that original SEB volume. It is a newscast-like account of the longest fortnight in scientific history (or perhaps 10 days since many areas in ageing research remain opaque) written for the student who is embarking on a career as a gerontologist or the specialist who has, perhaps by chance, blundered into the minefield of confused terminology and muddled debate that until recently characterized ageing research.

The thing which is most striking as a contemporary gerontologist looking back at the literature from the beginnings of the field is the complete absence of any organizing theoretical principles which would allow investigators to gain understanding (rather than simply experimental results) from the systems they chose to study. There seems to have been little consensus on what the ageing process actually was and this rendered discussion of any subsequent questions turbid to say the least. Some years before, Strehler (Strehler and Mildvan, 1960) had set out four principle criteria that defined the ageing process (or at least distinguished it from maturation and development) but there is little evidence from the 1967 SEB symposium that these were enthusiastically embraced by his contemporaries. Strehler defined ageing as a process which was:

• Universal (i.e. all members of a population of organisms will show it, a distinction from infectious disease);

• Progressive (the process was continual and incremental rather than sudden as in the case of ‘programmed’ organismal death);

• Intrinsic (distinguishing ageing from death due to outside events);

• Degenerative (this captures the idea that ageing is associated with both increasing chances of mortality but also an increasing level of morbidity).

Applying these criteria helps distinguish ageing from other pathological processes at work within organisms. However, they do not lay sufficient stress on one key aspect of the physiology of ageing, the increased frailty of old organisms compared to their young counterparts. Put simply, aged organisms often fail to survive physiological stresses which young organisms are able to weather effectively. For example, the budding yeast Saccharomyces cerevisiae reproduces asexually but shows an ageing process marked by the eventual cessation of reproductive capacity in older mother cells (Powell et al., 2003). If young and old cultures of yeast are exposed to an ageing that induces physiological stress (such as UV radiation), old yeast cells are markedly more prone to die (Kale and Jazwinski, 1996). In the nematode Caenorhabditis elegans, multiple mutations or interventions that lengthen the life of the animal also impart a stress resistance phenotype compared to wild-type controls (Gill et al., 2003). Many other examples of similar phenomena across the biosphere could be listed.

Understanding and dealing with human frailty, along with human morbidity, are both the major challenges facing modern gerontology and its primary justification as more than a disinterested search for the truth concerning our condition. Morbidity, the time spent sick before either death or recovery occurs, is prolonged, painful, expensive and undesirable for all concerned (it has been calculated that a 1% reduction in morbidity will result in savings of billions of pounds per year in long-term care costs by the middle third of this century). In contrast, death as a result of frailty can be both abrupt and apparently cheap (as in the case of death by infection in elderly humans following hip fracture); however, the fact that it falls on members of the population who are healthy, active and socially engaged means that it also has significant financial, as well as emotional, costs.

To venture upon a mechanistic analogy, ageing is the study of the biology of worn parts and the consequences thereof. But, before discussing the mechanisms of wear in more detail, it is necessary to consider briefly a question which has troubled many thinkers in human history: ‘why does ageing happen at all?’

2 Why does ageing happen?

Ageing is not universal across all species, or even among all metazoans, but it is extremely common and thus presumably provides some form of selective advantage to organisms that show it compared to those that do not. The theories I am about to present concerning ageing have been formulated with regard primarily to species that show a germ-line to soma distinction (the soma is the bits of you that are reading this chapter). Although a soma could, in principle, be either ageing or non-ageing the germ-line must, by definition, be immortal in order to allow the organism to contribute any offspring at all to future generations (an observation that appears to have been first made by the 19th-century evolutionary biologist August Weismann). These theories thus have only a tangential bearing on organisms that can reproduce clonally for extended periods (e.g. some plants). Nonetheless, at least some asexual metazoans do display an individual ageing process (Martínez and Levinton, 1992) and clonal lineages of these organisms can suffer a reduction of average fitness through time by the accumulation of slightly deleterious mutation which cannot be repaired without sexual recombination (a mechanism known as Muller’s Ratchet). Muller’s Ratchet should, in theory, drive purely asexual replicators to extinction unless the population is extremely large. However, many metazoan species that replicate clonally retain the ability to initiate sexual reproduction at specific time points (often generating germ-line from undifferentiated stem cells). Such organisms can thus be seen as opting in and out of the germline/soma distinction and when they are ‘in’ the evolutionary forces described below most definitely bite. The best current example of this is probably the cnidarian Hydra, which has been shown to be non-ageing in its asexual form (Martinez, 1998) but after sexual reproduction the population shows an exponential increase in mortality rate associated with functional deficits in cellularity, contractile movement and food capture in individual organisms (Yoshida et al., 2006).

Modern explanations for ‘why ageing happens’ are all based on the evolutionary truism that the force of natural selection declines with age. This means that, even in a population of immortal organisms, there are always far fewer chronologically old ones than young ones around (because the longer a given organism has been around the more likely it is to have been eaten, met with an accident, etc.). Thus, even though the reproductive ability of ‘old’ and ‘new’ non-ageing organisms is the same, the ‘old’ organisms contribute fewer offspring to the next generation than the ‘new’ organisms simply because there are fewer of them. Thus, any mutation that favours early life fecundity will be selected for even if it results in deleterious effects later on in the lifetime (a type of gene action termed antagonistic pleiotropy; Williams, 1957). This view of ageing argues against the operation of a ‘programme’ controlling the ageing of individuals (i.e. the existence of a genetic pathway or process that causes the organism to age but does nothing else). Rather, it suggests that ageing will result from an accumulation of unrepaired faults, which are generated at different rates in different tissues.

Antagonistic pleiotropy and related theories which conceptualize ageing as the by-product of selection for early-life fecundity (such as the ‘disposable soma’ theory of Thomas Kirkwood, which considers the problem in terms of resource allocation between somatic repair and reproduction) have proved highly satisfactory in explaining why ageing happens (Kirkwood, 2005). According to antagonistic pleiotropy, optimal lifespan is determined by selection pressure for maximum reproductive success. This is itself determined by the level of environmental risk (e.g. the chance of predation) to which members of the population are exposed as a consequence of the ecological niche which they occupy. The huge range of lifespans seen among organisms on this planet can thus be conceived of as points lying on a continuum between two opposing evolutionary strategies. Organisms at very high levels of risk tend to display ‘prodigal’ (or r selected) life history strategies marked by single reproductive events which generate many small and rapidly maturing young which then disperse without parental care. In contrast, species following ‘prudent’ (or K-selected) strategies tend to reproduce steadily and produce a few large young that receive intensive parental care and mature slowly. Clearly, prudence is only an option for a species whose members have a chance of making it to the end of the week in one piece. These models allow an or...

Table of contents

• EXPERIMENTAL BIOLOGY REVIEWS
• Contents
• Contributors
• Abbreviations
• Preface
• 1 What can we learn from the cross-species biology of ageing?
• 2 Rebirth and death: Nitric oxide and reactive oxygen species in seeds
• 3 Ageing and oxidants in the nematode Caenorhabditis elegans
• 4 The perception of reactive oxygen species in plants: The road to signal transduction
• 5 Mechanisms and genes controlling programmed cell death and Darwinian fitness in plants
• 6 Ageing research in the post-genome era: New technologies for an old problem
• 7 Telomeres, ageing and oxidation
• 8 A-type lamins, disease and ageing: A stress-induced relationship?
• 9 Role of the glyoxalase pathway in delaying plant senescence under stress conditions
• 10 Catalase regulation during leaf senescence of Arabidopsis
• 11 Atmospheric CO2 signalling, cellular redox state and plant growth and development
• 12 Protein damage in the ageing process: Advances in quantitation and the importance of enzymatic defences
• Index