[
Aging Cell,
2002]
The papers by Van Voorhies in Free Radical Biology & Medicine (33, 587-596, 2002) and in this journal claim that the major longevity-extending mutations in C. elegans essentially act by reducing metabolic rate as predicted by the rate-of-living theory, and do not alter any metabolically independent mechanism specific to aging. In contrast, we found no evidence of a reduction in metabolic rate in these mutants using different experimental approaches. Now, Van Voorhies challenges the accuracy of our experimental results.
[
Aging Cell,
2002]
The reviews by Braechman et al. and Van Voorhies in this issue of Aging Cell concur on the potential importance of metabolic rate and function to longevity in C. elegans. These reviews differ though, on their assessment of whether long-lived C. elegans mutants have a reduced metabolic rate compared to wild-type worms. At the centre of this disagreement are two main issues: the importance of measurement conditions when conducting metabolic assays on C. elegans, and which techniques are appropriate for measuring the metabolic rate of an organism and subsequent analysis of such data. These issues are interconnected; if the conditions under which an organism's metabolic rate are measured have a large impact on the resulting data, conclusions drawn from data collected from animals under different conditions may be invalid irrespective of the validity of the measurement methods. Conversely, measurement techniques which produce spurious data cannot be used to draw accurate conclusions about the metabolic rate of an organism, regardless of the conditions under which the organism was maintained.
[
Nat Genet,
1992]
Human pre-B cell acute lymphoblastic leukaemias are associated with a chimaeric gene that is generated from a t(1;19) chromosomal translocation. This fusion joins the regulatory regions of the lymphoid transcription factor gene, E2A, to the C-terminal region, including the homeodomain, of PBX1 (previously called prl). Tow additional human genes (PBX2 and PBX3) with 77-84% identity to PBX1 have been isolated based on sequence similarity. These genes, however, are too closely related to distinguish between recent divergence and conserved essential motifs, if any, outside the homeodomain. Such conserved domains might be revealed by comparing mammalian sequences with those of more evolutionarily distant organisms, such as the expressed sequence tags (ESTs) generated recently in Caenorhabditis elegans.