There are three basic levels of control of aging: 1) the proximate causes leading to senesence in particular cell lines or tissues, 2) the regulatory processes that integrate the cell and tissue specific patterns into an individual's life history, and 3) the evolutionary forces that select upon life history traits to determine the aging pattern characteristic of the species. In the past we have studied the control of aging at all three levels with the abnormal abdomen (aa) syndrome in Drosophila mercatorum. Recently, we have extended this integrated, multi-level approach study the aging phenotypes associated with insertion-induced bobbed (bb) flies in the closely related species, D. hydei. Aa and bb show many similarities; both are associated with homologous inserts that go into the coding region of the 28S ribosomal genes, both seem to induce a fuctional ribosomal deficiency in polytene tissue, both lead to phenotypes that appear to be due to lower activities of juvenile hormone esterase, and both are adaptive under desiccating conditions in nature because of their effects upon adult sexual maturation and longevity. Despite these many parallels, the aging effects associated with aa are controlled at the molecular level through somatic overreplication (or its failure) of noninserted 28S genes during formation of the fat body, the polytene tissue that produces the juvenile hormone esterase. In contrast, preliminary data indicate that bb in hydei is controlled by adjusting the number of inserted to noninserted 28S genes in the germ-line. By performing our studies on both species, we can not only learn how aging is controlled at several different levels of biological organization, but we also hope to ultimately answer the question as to why two such closely related species have utilized such different molecular routes to achieve similar development, physiological and ecological ends with respect to their aging patterns.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Arts and Sciences
Saint Louis
United States
Zip Code
Saa, Paula; Castilla, Joaquin; Soto, Claudio (2006) Ultra-efficient replication of infectious prions by automated protein misfolding cyclic amplification. J Biol Chem 281:35245-52
Saa, Paula; Castilla, Joaquin; Soto, Claudio (2006) Presymptomatic detection of prions in blood. Science 313:92-4
Castilla, Joaquin; Saa, Paula; Morales, Rodrigo et al. (2006) Protein misfolding cyclic amplification for diagnosis and prion propagation studies. Methods Enzymol 412:3-21
Bieler, Sylvain; Estrada, Lisbell; Lagos, Rosalba et al. (2005) Amyloid formation modulates the biological activity of a bacterial protein. J Biol Chem 280:26880-5
Castilla, Joaquin; Saa, Paula; Soto, Claudio (2005) Detection of prions in blood. Nat Med 11:982-5
Lawler, S H; Sussman, R W; Taylor, L L (1995) Mitochondrial DNA of the Mauritian macaques (Macaca fascicularis): an example of the founder effect. Am J Phys Anthropol 96:133-41
Hollocher, H; Templeton, A R (1994) The molecular through ecological genetics of abnormal abdomen in Drosophila mercatorum. VI. The non-neutrality of the Y chromosome rDNA polymorphism. Genetics 136:1373-84
Templeton, A R; Hollocher, H; Johnston, J S (1993) The molecular through ecological genetics of abnormal abdomen in Drosophila mercatorum. V. Female phenotypic expression on natural genetic backgrounds and in natural environments. Genetics 134:475-85
Hollocher, H; Templeton, A R; DeSalle, R et al. (1992) The molecular through ecological genetics of abnormal abdomen. IV. Components of genetic variation in a natural population of Drosophila mercatorum. Genetics 130:355-66
Templeton, A R; Hollocher, H; Lawler, S et al. (1989) Natural selection and ribosomal DNA in Drosophila. Genome 31:296-303

Showing the most recent 10 out of 18 publications