50 results found
Davies SK, Bundy JG, Leroi AM, 2015, Metabolic Youth in Middle Age: Predicting Aging in Caenorhabditis elegans Using Metabolomics, Journal of Proteome Research, Vol: 14, Pages: 4603-4609, ISSN: 1535-3907
Many mutations and allelic variants are known that influence the rate at which animals age. But when in life do such variants diverge from normal patterns of ageing? And is this divergence visible in their physiologies? To investigate these questions we have used 1H NMR spectroscopy to study how the metabolome of the nematode Caenorhabditis elegans changes as it grows older. We identify a series of metabolic changes that, collectively, predict the age of wild-type worms. We then show that long-lived mutant daf-2(m41) worms are metabolically youthful compared to wild-type worms - but that this relative youth only appears in middle age. Finally, we show that metabolic age predicts the timing and magnitude of differences in age-specific mortality between these strains. Thus the future mortality of these two genotypes can be predicted long before most of the worms die.
Aging is a complex process, which involves changes in different cellular functions that all can be integrated on the metabolite level. This means that different gene regulation pathways that affect aging might lead to similar changes in metabolism and result in a metabolic signature of senescence. In this chapter, we describe how to establish a metabolic signature of senescence by analyzing the metabolome of various longevity mutants of the model organism Caenorhabditis elegans using gas chromatography-mass spectrometry (GC-MS). Since longevity-associated genes exist for other model organisms and humans, this analysis could be universally applied to body fluids or whole tissue samples for studing the relationship between senescence and metabolism.
MacCallum RM, Mauch M, Burt A, et al., 2012, Evolution of music by public choice, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 12081-12086, ISSN: 0027-8424
Davies SK, Leroi AM, Bundy JG, 2012, Fluorodeoxyuridine affects the identification of metabolic responses to daf-2 status in Caenorhabditis elegans, MECHANISMS OF AGEING AND DEVELOPMENT, Vol: 133, Pages: 46-49, ISSN: 0047-6374
Casadevall i Solvas X, Geier FM, Leroi AM, et al., 2011, High-throughput age synchronisation of Caenorhabditis elegans, Chemical Communications, Vol: 47, Pages: 9801-9803
We present a passive microfluidic strategy for sorting adult C. elegans nematodes on the basis of age and size. The separation mechanism takes advantage of phenotypic differences between ‘adult’ and ‘juvenile’ organisms and their behaviour in microfluidic architectures. In brief, the microfluidic device allows worms to sort themselves in a passive manner.
Geier FM, Want EJ, Leroi AM, et al., 2011, Cross-Platform Comparison of Caenorhabditis elegans Tissue Extraction Strategies for Comprehensive Metabolome Coverage, ANALYTICAL CHEMISTRY, Vol: 83, Pages: 3730-3736, ISSN: 0003-2700
Rebbeck CA, Leroi AM, Burt A, 2011, Mitochondrial Capture by a Transmissible Cancer, SCIENCE, Vol: 331, Pages: 303-303, ISSN: 0036-8075
Fuchs S, Bundy JG, Davies SK, et al., 2010, A metabolic signature of long life in Caenorhabditis elegans, BMC BIOLOGY, Vol: 8, ISSN: 1741-7007
Thomas R, Rebbeck C, Leroi AM, et al., 2009, Extensive conservation of genomic imbalances in canine transmissible venereal tumors (CTVT) detected by microarray-based CGH analysis, CHROMOSOME RESEARCH, Vol: 17, Pages: 927-934, ISSN: 0967-3849
Swire J, Fuchs S, Bundy JG, et al., 2009, The cellular geometry of growth drives the amino acid economy of Caenorhabditis elegans, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 276, Pages: 2747-2754, ISSN: 0962-8452
Leroi AM, 2008, Creationism and its critics in antiquity, NATURE, Vol: 452, Pages: 153-153, ISSN: 0028-0836
Tain LS, Lozano E, Saez AG, et al., 2008, Dietary regulation of hypodermal polyploidization in C-elegans, BMC DEVELOPMENTAL BIOLOGY, Vol: 8, ISSN: 1471-213X
Leroi AM, 2007, Armand Leroi - Q&A, Current Biology, Vol: 17, Pages: R619-R620, ISSN: 0960-9822
Leroi AM, 2006, The future of neo-eugenics., EMBO Reports, Vol: 7, Pages: 1184-1187, ISSN: 1469-221X
Lozano E, Sáez AG, Flemming AJ, et al., 2006, Regulation of growth by ploidy in Caenorhabditis elegans., Current Biology, Vol: 16, Pages: 493-498, ISSN: 0960-9822
Some animals, such as the larvae of Drosophila melanogaster, the larvae of the Appendicularian chordate Oikopleura, and the adults of the nematode Caenorhabditis elegans, are unusual in that they grow largely by increases in cell size. The giant cells of such species are highly polyploid, having undergone repeated rounds of endoreduplication. Since germline polyploid strains tend to have large cells, it is often assumed that endoreduplication drives cell growth, but this remains controversial. We have previously shown that adult growth in C. elegans is associated with the endoreduplication of nuclei in the epidermal syncitium, hyp 7. We show here that this relationship is causal. Manipulation of somatic ploidy both upwards and downwards increases and decreases, respectively, adult body size. We also establish a quantitative relationship between ploidy and body size. Finally, we find that TGF-beta (DBL-1) and cyclin E (CYE-1) regulate body size via endoreduplication. To our knowledge, this is the first experimental evidence establishing a cause-and-effect relationship between somatic polyploidization and body size in a metazoan.
Leroi AM, Swire J, 2006, The recovery of the past, WORLD OF MUSIC, Vol: 48, Pages: 43-54, ISSN: 0043-8774
Leroi AM, 2005, On human diversity, The Scientist, Vol: 19, Pages: 16-17, ISSN: 0890-3670
The past 50 years have seen the scientific community shun any discussion of the causes of normal physical variety in humans. This is primarily because scientists have attempted to remove the concept of race from scientific study. Despite the mass of knowledge regarding the diversity of blood types, allozymes, mitochondrial DNA, the Y chromosome and single nucleotide polymorphisms (SNPs),we know little about what causes of normal physical variety. We know very little about why the Dinka of the Sudan are so tall and African pygmies so small,why the Yakut of Siberia have such high basal metabolic rates, why the Sea Gypsies of Indonesia can see so well underwater, why the Yoruba of Nigeria have so many dizygotic twins, or even why the colors of our skin, eyes, and hair vary across the globe.
Leroi AM, 2005, A family tree in every gene, JOURNAL OF GENETICS, Vol: 84, Pages: 3-6, ISSN: 0022-1333
Leroi AM, Bartke A, De Benedictis G, et al., 2005, What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?, MECHANISMS OF AGEING AND DEVELOPMENT, Vol: 126, Pages: 421-429, ISSN: 0047-6374
Leroi AM, 2004, Biased embryos and evolution, NATURE, Vol: 430, Pages: 294-294, ISSN: 0028-0836
Braun V, Azevedo RBR, Gumbel M, et al., 2003, ALES: cell lineage analysis and mapping of developmental events, BIOINFORMATICS, Vol: 19, Pages: 851-858, ISSN: 1367-4803
Leroi AM, Koufopanou V, Burt A, 2003, Cancer selection, NATURE REVIEWS CANCER, Vol: 3, Pages: 226-231, ISSN: 1474-175X
Leroi AM, 2003, Mutants: on the form, variety and errors of the the Human body, New York, Publisher: Viking Penguin
Azevedo RBR, Keightley PD, Lauren-Maatta C, et al., 2002, Spontaneous mutational variation for body size in Caenorhabditis elegans, GENETICS, Vol: 162, Pages: 755-765, ISSN: 0016-6731
Morita K, Flemming AJ, Sugihara Y, et al., 2002, A Caenorhabditis elegans TGF-beta, DBL-1, controls the expression of LON-1, a PR-related protein, that regulates polyploidization and body length, EMBO JOURNAL, Vol: 21, Pages: 1063-1073, ISSN: 0261-4189
Patel MN, Knight CG, Karageorgi C, et al., 2002, Evolution of germ-line signals that regulate growth and aging in nematodes, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 99, Pages: 769-774, ISSN: 0027-8424
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