ABSTRACT:

Telomeres are repetitive sequences of DNA forming the ends of chromosomes in eukaryotic organisms and are the focus of human aging studies. Cells accumulate wear and tear from day to day use, so they replicate, but their DNA can accumulate damage over time and be multiplied with each cell replication with harmful effects on the organism. Telomeres are thought to limit the lifespan of cells by ‘counting’ the number of cell replication events and triggering cell senescence or death when the maximum number of safe cell replications has been reached. Over time, these senescent cells accumulate and produce the physical signs of aging. However, tests of this hypothesis in non-model organisms do not support predictions suggesting the predominant theory of telomeres and aging is incomplete.

In chapter 1, I propose an alternative hypothesis of telomere function and its relationship to stress and aging called, “The Telomere Hypothesis of Stress and Aging” (THSA) which incorporates an additional, previously underappreciated telomere function—their role in modulating expression of stress response genes. Genomic DNA is compacted into chromatin—a complex folding architecture which alters the activity of particular genes. Environmental stress triggers telomere shortening, cell metabolism slows, chromatin unfolds, and stress response genes are upregulated. Following chromatin remodeling some telomeres are re-lengthened and cell metabolism increases. Thus, the THSA predicts dynamic telomere length and cell metabolic rate that are related to levels of environmental stress exposure. In addition to formalizing the Telomere Hypothesis of Stress and Aging (THSA),

If birds have higher levels of ALT than observed in mammals they should also have a greater capacity to re-lengthen telomeres in general. Thus, according to predictions of the THSA, on a gram for gram basis, birds are expected to lose telomeres more slowly with age than mammals. Whether or not this is true was previously unknown. I examine this question in Chapter 2; by comparing the rates of telomere loss with age between birds and mammal species. When comparing rates of telomere loss with age between birds and mammals, results were as predicted—for a given body size, birds lost telomeres with age at slower rates than mammals. Thus, results support the THSA—if birds possess higher rates of ALT this may account for their ability to achieve longer lifespans for the body size and metabolic rate. Longer-lived species of birds and mammals lost telomeres with age at slower rates than short lived ones. This is consistent with both the predominant paradigm and the THSA, except the THSA predicts a portion of telomere shortening with age is due to increasing up-regulation of stress response genes with age.