Abstract

The long-term goal of our studies is to understand the molecular and genetic elements that underlie the process of aging and determine longevity.
The aim of this proposal is to examine how mutations in a single gene, Indy, lead to a dramatic increase in life span in Drosophila melanogaster. We present data on the isolation and initial characterization of three independent P-element insertional mutations in the same gene, Indy, which cause a large increase in life span, and show that excision of the insert leads to reversion to a normal life span. The distribution of expression of the Indy gene, primarily in the fat body and oenocytes, and predicted sequence of the Indy protein, suggest that Indy may be playing a role in intermediary metabolism. The molecular and genetic analyses indicate that a partial reduction in the activity of this gene is responsible for an extension in life span, while a more severe reduction is detrimental to long life. The molecular, genetic, and physiological studies in this proposal will help provide an understanding of how an alteration in this single gene can lead to such a profound effect on increasing longevity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG016667-03
Application #
6372317
Study Section
Special Emphasis Panel (ZAG1-PKN-2 (J1))
Program Officer
Mccormick, Anna M
Project Start
1999-04-01
Project End
2004-03-31
Budget Start
2001-05-01
Budget End
2002-03-31
Support Year
3
Fiscal Year
2001
Total Cost
$327,817
Indirect Cost

  Institution

Name
University of Connecticut
Department
Dentistry
Type
Schools of Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Wood, Jason G; Schwer, Bjoern; Wickremesinghe, Priyan C et al. (2018) Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster. Proc Natl Acad Sci U S A 115:1564-1569
von Loeffelholz, Christian; Lieske, Stefanie; Neuschäfer-Rube, Frank et al. (2017) The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism. Hepatology 66:616-630
Jones, Brian C; Wood, Jason G; Chang, Chengyi et al. (2016) A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan. Nat Commun 7:13856
Wood, Jason G; Jones, Brian C; Jiang, Nan et al. (2016) Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila. Proc Natl Acad Sci U S A 113:11277-11282
Ding, Feifei; Gil, M Pilar; Franklin, Michael et al. (2014) Transcriptional response to dietary restriction in Drosophila melanogaster. J Insect Physiol 69:101-6
Zhu, Chen-Tseh; Chang, Chengyi; Reenan, Robert A et al. (2014) Indy gene variation in natural populations confers fitness advantage and life span extension through transposon insertion. Aging (Albany NY) 6:58-69
Whitaker, Rachel; Gil, M Pilar; Ding, Feifei et al. (2014) Dietary switch reveals fast coordinated gene expression changes in Drosophila melanogaster. Aging (Albany NY) 6:355-68
Whitaker, Rachel; Faulkner, Shakeela; Miyokawa, Reika et al. (2013) Increased expression of Drosophila Sir2 extends life span in a dose-dependent manner. Aging (Albany NY) 5:682-91
Savva, Yiannis A; Jepson, James E C; Chang, Yao-Jen et al. (2013) RNA editing regulates transposon-mediated heterochromatic gene silencing. Nat Commun 4:2745
Rogina, Blanka; Helfand, Stephen L (2013) Indy mutations and Drosophila longevity. Front Genet 4:47

Showing the most recent 10 out of 35 publications