Rotifers are a potentially valuable new model to investigate the mechanisms of aging, as well as homeostasis and tissue regeneration, the effects of reproductive mode (asexual versus sexual) on longevity, and the cellular and molecular processes of senescence. Moreover, as basal metazoans, rotifers may share more genes with humans than Ecdyzoan animal models like C. elegans and D. melanogaster. In the proposed work we identify new genes associated with rotifer aging and search for their homologs in humans. Monogonont rotifers have specific features that make them an attractive models for aging studies, including: 1) a history of aging related research extending back nearly a century;2) asexual propagation of clonal cultures, so that experiments can take place in the same genetic background, without the potential inbreeding depression imposed on isogenic lines;3) sexual and asexual reproduction in the same genetic background;4) haploid males, allowing direct expression of alleles and simplifying crosses in the absence of complex marker chromosomes;5) production of highly stable diapausing eggs;5) many closely related strains and species that differ in life history traits;and 6) A well developed tool box of genetic resources including partially sequenced genomes and transcriptomes, and a working RNAi protocol. In the proposed work, we determine the effects on aging and longevity of dietary restriction, oxidative stress, and elevated temperature in five closely related strains of the Brachionus plicatilis species complex. The effect of sexual and asexual reproduction on aging also is investigated and correlated with cumulative oxidative damage to proteins, lipids, and DNA. We also identify genes involved in aging and longevity by examining the transcription profiles of rotifers of different ages under different dietary, reproductive, and stress conditions, and confirm the activity of specific genes by RNAi and qtPCR. The role of diapause in aging also is investigated by examining the mechanisms by which diapause in Brachionus alters tissue homeostasis, suspends metabolism during dormancy, and stimulates tissue repair following dormancy. The degree of aging observed in rotifers that have been kept in a dormant state for up to 25 years also is examined.

Public Health Relevance

Rotifers are a valuable new invertebrate model to investigate the mechanisms of aging, including homeostasis and tissue regeneration, the effects of reproductive mode (asexual versus sexual) and diapause on longevity, and the cellular and molecular processes of senescence. Because of their phylogenetic relationship to humans and other animals, they can be useful in the identification of genes that regulate aging. Identifying evolutionarily conserved genes in Ecdysozoan and spiralian phyla that regulate organismal aging could provide attractive targets for pharmacological intervention in mammalian aging. Molecular understanding of how dietary restriction extends lifespan will have direct implications for new approaches to treat metabolic diseases like diabetes and obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG037960-04
Application #
8529420
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (M1))
Program Officer
Murthy, Mahadev
Project Start
2010-09-01
Project End
2015-05-31
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$279,150
Indirect Cost
$42,529
Name
Georgia Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
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Gribble, Kristin E; Jarvis, George; Bock, Martha et al. (2014) Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring. Aging Cell 13:623-30
Snell, Terry W; Johnston, Rachel K; Rabeneck, Brett et al. (2014) Joint inhibition of TOR and JNK pathways interacts to extend the lifespan of Brachionus manjavacas (Rotifera). Exp Gerontol 52:55-69
Gribble, Kristin E; Kaido, Oksana; Jarvis, George et al. (2014) Patterns of intraspecific variability in the response to caloric restriction. Exp Gerontol 51:28-37
Snell, Terry W (2014) Rotifers as models for the biology of aging. International review of hydrobiology 99:84-95
Smith, Hilary A; Snell, Terry W (2014) Differential evolution of asexual and sexual females in a benign culture environment. International review of hydrobiology 99:117-124
Gribble, Kristin E; Welch, David B Mark (2013) Life-span extension by caloric restriction is determined by type and level of food reduction and by reproductive mode in Brachionus manjavacas (Rotifera). J Gerontol A Biol Sci Med Sci 68:349-58
Snare, David J; Fields, Allison M; Snell, Terry W et al. (2013) Lifespan extension of rotifers by treatment with red algal extracts. Exp Gerontol 48:1420-7
Snell, Terry W; Fields, Allison M; Johnston, Rachel K (2012) Antioxidants can extend lifespan of Brachionus manjavacas (Rotifera), but only in a few combinations. Biogerontology 13:261-75