A Critical Evaluation of Nonmammalian Models for Aging Research

The newly developed analytical techniques for reconstructing evolutionary divergence patterns from molecular sequence data, combined with the virtual avalanche of new DNA sequences from a multitude of organisms, has altered traditional views of large-scale phylogenetic relationships within multicellular animals. A clear pattern in comparing life-extending genetic alterations in worms, flies, and mice is that mutations in worms and flies typically have a greater effect on longevity. Another feature of fly and worm biology that is common in molting animals is that adult somatic cells are virtually all postmitotic. Proliferative homeostasis is the maintenance of tissue or organ functional integrity by a precise balance between cell loss and cell replacement. Loss of this homeostasis can lead to critical tissue atrophy or, more commonly, the development of tumors. Worms display the very unusual property of eutely-that is, they determinate somatic cell number in any life stage. This phenomenon is unusual even within nematodes. Thus, all adult worm hermaphrodites have 959 somatic nuclei, of which 302 are neurons and 95 are striated muscle cells. During development, 131 cells die. The lineage of each cell in the adult body is nearly invariant.