UC Irvine

The search for a diet or supplement that improves healthspan in humans has been daunting. This dissertation applies theory on the evolution of aging to understand what diets are best for extending healthspan. Chapter 1 reviews strategies for healthspan extension using diet and supplementation from the standpoint of evolutionary biology. Then it introduces a new evolutionary strategy for dietary enhancement of healthspan. Our intuitive understanding of adaptation by natural selection is dominated by the power of selection at early ages in large populations. Yet, as the forces of natural selection fall with adult age, we expect adaptation to be attenuated with age. Explicit simulations of age-dependent adaptation suggest that populations adapt to a novel environment quickly at early ages, but only slowly and incompletely at later adult ages. Chapter 2 tests for age-dependent adaptation in laboratory populations of Drosophila melanogaster. The results show clear age-specificity of adaptation in two examples of evolution in response to dietary transition. In the first example, populations perform better on an ancestral, long-abandoned, fruit diet compared to an evolutionarily recent fruit diet, only at later ages. In the second example, the gain and loss of urea adaptation is strongest at early ages and weakest at later ages. Chapter 3 evaluates the effects of combining both diet and botanical supplementation on Drosophila healthspan. One botanical extract, derived from Rosa damascena, decreases survivorship when added to an ancestral diet, but increases lifespan when added to an evolutionarily recent diet. Another botanical, derived from Rhodiola rosea, extends life-span by approximately 20% with a 20% decrease in average fecundity. In addition, there is evidence of an antagonistic effect when these botanicals are combined, supporting the “Poisoned Chalice” hypothesis that novel combinations of substances may produce adverse physiological responses. Chapter 4 studies the effects of evolutionary history on phenotypic convergence in D. melanogaster populations selected for desiccation resistance and larval urea tolerance. We find that extreme selection can have long-lasting impacts on phenotypic differentiation, particularly for longevity, even after a few hundred generations of relaxed selection.