Do telomere dynamics link lifestyle and lifespan?

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Identifying and understanding the processes that underlie the observed variation in lifespan within and among species remains one of the central areas of biological research. Questions directed at how, at what rate and why organisms grow old and die link disciplines such as evolutionary ecology to those of cell biology and gerontology. One process now thought to have a key role in ageing is the pattern of erosion of the protective ends of chromosomes, the telomeres. Here, we discuss what is currently known about the factors influencing telomere regulation, and how this relates to fundamental questions about the relationship between lifestyle and lifespan.

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Life-history tradeoffs and telomeres

The concept of tradeoffs is central to our understanding of the evolution of life histories. Because resources, and the time it takes to acquire them, are limiting, high expenditure on one life-history trait has negative consequences for other traits requiring the same resources. Explanations of differences within and among species in life-history strategies are generally framed in terms of differences in the optimal resource investment in growth, reproduction and self-maintenance. Hence, we

What are telomeres and what do they do?

Telomeres form the ends of eukaryotic chromosomes (Box 1) and are currently thought to have a variety of functions. They provide the cell with a mechanism for distinguishing between real chromosome ends and those arising from chromosome breaks that need to be repaired. They also protect the encoding parts of the chromosomes from the loss of nucleotides that occurs because chromosome ends are not replicated completely during cell division (Box 2). Telomeres also appear to have a role in the

Consequences of telomere loss

Telomere loss puts a finite limit on the reproductive life of cells. Each time a cell divides, the telomeric DNA on its chromosomes gets shorter (Box 2), unless it is restored; once some crucial length is reached, the telomere becomes dysfunctional and the protective capping of chromosome ends provided by telomeres (Box 1) no longer operates. Telomeres can also become dysfunctional owing to direct DNA damage or changes in the telomere-associated proteins [9]. Dysfunctional telomeres make the

Telomeres and immortality

Telomeres can be restored by telomerase or its equivalent (Box 3). So, why then do all cells not maintain telomere length and, therefore, their replicative potential? Multicellular animals contain in their soma variable amounts of post-mitotic cells, which do not divide, and mitotically active cells that do. In relatively simple organisms, such as Caenorhabditis elegans and Drosophila melanogaster, nondividing cells predominate in the adult body. In more complex groups, such as vertebrates,

Telomeres and age

Telomere shortening used to be thought of as occurring at a constant rate, hence the suggestion that telomeres represented a ‘mitotic clock’, the reading of which would give information about the replicative past and future of a cell [15]. It was therefore hoped that telomere length could be used as an indicator of the age of an organism [21]. In several organisms, including humans, there is some correlation between age and average telomere length in at least some tissues (e.g. Figure 1, Figure

Telomeres and lifespan

The big question in the context of life-history tradeoffs is how these changes at the cellular level influence organism performance. Telomere loss and maintenance both have costs and benefits that need to be balanced (Figure 3), and we need to understand the extent to which managing the pattern and pace of telomere loss and restoration is likely to be important in determining lifespan. The replicative potential of cells in culture is positively related to the longevity of the species from

Telomeres and lifestyle

The rate of telomere loss is sensitive to cell division rates and to environmental circumstances in the cell, particularly the level of oxidative stress (Box 2), and this potentially provides an important link between lifestyle and senescence. Telomeres are not simple cell division or time counters. The absence of tight relationships between age and telomere length within species is due at least partly to the fact that telomeres give a handle on biological (rather than chronological) age at the

What next?

Measures of relative telomere lengths could offer organismal biologists a molecular marker of individual history and current state, and a useful measure of the effects of various investment patterns on potential lifespan. More information is needed on what causes telomere changes in different tissues and how this affects organism survival prospects. Although our understanding of processes at the cellular level is moving forward fast, from an evolutionary and life-history perspective, there is a

Acknowledgements

We thank Neil Metcalfe, Lubna Nasir and Carol Vleck for helpful discussions and comments, and NERC, NSF and NIH for grant support.

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