Invertebrates in the Study of Aging

Here I'll point out a review of some of the species researchers use in the study of aging, coupled with a call to expand that list to fill in known gaps and shortcomings. Despite the large differences between lower animals and humans, aging is a near universal phenomenon. It originated in its presently dominant form very early in the evolution of life, and thus many relevant cellular mechanisms are the same or at least very similar even in widely divergent species. Since lower animals used in aging research are short-lived, it is far less costly to conduct exploratory life span experiments and alterations of metabolism. Nonetheless, there are sizable challenges inherent in trying to learn about human aging via the investigation of insects and worms, and here it is proposed the some of these problems can be overcome by adding additional points of comparison, such as hydra, sea urchins, sea squirts, and the like:

Although the nematode, the fruit fly models, and yeast have led to major advances in aging research, the gaps that exist in these models make a compelling case for additional, potentially invertebrate, model systems to identify longevity genes, whose roles have yet to be studied, and to investigate the role of additional cellular pathways in aging.

Both the nematode and the fruit fly models have critical shortcomings including the following: (a) both nematode and fruit fly belong to Ecdysozoa, a superphylum, which has undergone extensive gene loss since their divergence from their common ancestor with humans and thus a large fraction of human orthologs are missing; (b) larvae from these two species can enter a non-aging stage in response to stress, which suggests that modulation of lifespan observed in corresponding adult organisms may be mediated by stress response mechanisms that have no equivalent in humans; (c) except for the Drosophila gut, the somatic adult tissues of these two organisms have limited regenerative capabilities with scarce to null cell proliferation; finally, (d) nematodes and fruit flies poorly mimic the processes involving stem cell renewal and tissue repair mechanisms that maintain tissue homeostasis in mammals. Thus, new invertebrate models with proliferating cells in the adult, as well as in those with extensive regenerative capacity, have the potential to be informative on the perils of life-long cell division and mechanisms of tissue regeneration and homeostasis.

Given this background, researchers have begun to make new inroads in the study of aging and longevity in several new model systems. We provide here a brief outline of the advantages of several of the newest invertebrate model systems for the study of aging. Although we continue to witness remarkable progress in aging research using invertebrate models, major limitations and challenges remain in the use of these new models for research in aging biology. These limitations include: (a) technologies to mass culture cells from these models are still lacking; (b) progress has been slow in fine tuning genetic and molecular tools and methodologies, including RNAi and transgenic approaches, for use in these models; (c) very few age-related phenotypes that are functions of specific cellular and molecular pathways in these systems have been identified; and, (d) information on cellular, molecular, and physiological mechanisms in tissue aging and homeostasis, including the role of stem cells and senescence, is still very meager in these new model systems.



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