Tissue-specific Transcriptome Profiling of Reveals Roles for GATA Transcription Factors in Longevity by Dietary Restriction

Overview

Journal NPJ Aging Mech Dis

Specialty Geriatrics

Date 2018 Apr 21

PMID 29675265

Citations 23

Authors

Adam J Dobson

Xiaoli He

Eric Blanc

Ekin Bolukbasi

Yodit Feseha

Mingyao Yang

Matthew D W Piper

Affiliations

Soon will be listed here.

Abstract

Dietary restriction (DR) extends animal lifespan, but imposes fitness costs. This phenomenon depends on dietary essential amino acids (EAAs) and TOR signalling, which exert systemic effects. However, the roles of specific tissues and cell-autonomous transcriptional regulators in diverse aspects of the DR phenotype are unknown. Manipulating relevant transcription factors (TFs) specifically in lifespan-limiting tissues may separate the lifespan benefits of DR from the early-life fitness costs. Here, we systematically analyse transcription across organs of subjected to DR or low TOR and predict regulatory TFs. We predict and validate roles for the evolutionarily conserved GATA family of TFs, and identify conservation of this signal in mice. Importantly, restricting knockdown of the GATA TF to specific fly tissues recapitulated the benefits but not the costs of DR. Together, our data indicate that the GATA TFs mediate effects of dietary amino acids on lifespan, and that by manipulating them in specific tissues it is possible to reap the fitness benefits of EAAs, decoupled from a cost to longevity.

Citing Articles

Undernutrition-induced stunting-like phenotype in .

Putri T, Wahyudin E, Pratama M, Fatiah D, Hardiyanti W, Chaeratunnisa R Narra J. 2025; 4(3):e999.

PMID: 39816060 PMC: 11731816. DOI: 10.52225/narra.v4i3.999.

Rapamycin's lifespan effect is modulated by mito-nuclear epistasis in Drosophila.

Ibrahim R, Bahilo Martinez M, Dobson A Aging Cell. 2024; 23(12):e14328.

PMID: 39225061 PMC: 11634709. DOI: 10.1111/acel.14328.

Sex, tissue, and mitochondrial interactions modify the transcriptional response to rapamycin in Drosophila.

Raynes Y, Santiago J, Lemieux F, Darwin L, Rand D BMC Genomics. 2024; 25(1):766.

PMID: 39107687 PMC: 11304892. DOI: 10.1186/s12864-024-10647-x.

Translational regulation enhances distinction of cell types in the nervous system.

Ichinose T, Kondo S, Kanno M, Shichino Y, Mito M, Iwasaki S Elife. 2024; 12.

PMID: 39010741 PMC: 11251722. DOI: 10.7554/eLife.90713.

Queen bee gut microbiota extends honeybee lifespan by inhibiting insulin signaling.

Wang H, Chen W, Lei L, Zhang W, Liu Z, Wang Y Appl Environ Microbiol. 2024; 90(4):e0179923.

PMID: 38470148 PMC: 11022582. DOI: 10.1128/aem.01799-23.

References

Tiebe M, Lutz M, De La Garza A, Buechling T, Boutros M, Teleman A . REPTOR and REPTOR-BP Regulate Organismal Metabolism and Transcription Downstream of TORC1. Dev Cell. 2015; 33(3):272-84. PMC: 4430829. DOI: 10.1016/j.devcel.2015.03.013. View

Vilchez D, Simic M, Dillin A . Proteostasis and aging of stem cells. Trends Cell Biol. 2013; 24(3):161-70. DOI: 10.1016/j.tcb.2013.09.002. View

Herrmann C, Van de Sande B, Potier D, Aerts S . i-cisTarget: an integrative genomics method for the prediction of regulatory features and cis-regulatory modules. Nucleic Acids Res. 2012; 40(15):e114. PMC: 3424583. DOI: 10.1093/nar/gks543. View

Grandison R, Piper M, Partridge L . Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature. 2009; 462(7276):1061-4. PMC: 2798000. DOI: 10.1038/nature08619. View

Okumura T, Takeda K, Kuchiki M, Akaishi M, Taniguchi K, Adachi-Yamada T . GATAe regulates intestinal stem cell maintenance and differentiation in Drosophila adult midgut. Dev Biol. 2016; 410(1):24-35. DOI: 10.1016/j.ydbio.2015.12.017. View

Attardo G, Higgs S, Klingler K, Vanlandingham D, Raikhel A . RNA interference-mediated knockdown of a GATA factor reveals a link to anautogeny in the mosquito Aedes aegypti. Proc Natl Acad Sci U S A. 2003; 100(23):13374-9. PMC: 263821. DOI: 10.1073/pnas.2235649100. View

Lex A, Gehlenborg N, Strobelt H, Vuillemot R, Pfister H . UpSet: Visualization of Intersecting Sets. IEEE Trans Vis Comput Graph. 2015; 20(12):1983-92. PMC: 4720993. DOI: 10.1109/TVCG.2014.2346248. View

Dutta D, Dobson A, Houtz P, Glasser C, Revah J, Korzelius J . Regional Cell-Specific Transcriptome Mapping Reveals Regulatory Complexity in the Adult Drosophila Midgut. Cell Rep. 2015; 12(2):346-58. DOI: 10.1016/j.celrep.2015.06.009. View

Solon-Biet S, Walters K, Simanainen U, McMahon A, Ruohonen K, Ballard J . Macronutrient balance, reproductive function, and lifespan in aging mice. Proc Natl Acad Sci U S A. 2015; 112(11):3481-6. PMC: 4371964. DOI: 10.1073/pnas.1422041112. View

10.

Zhang P, Judy M, Lee S, Kenyon C . Direct and indirect gene regulation by a life-extending FOXO protein in C. elegans: roles for GATA factors and lipid gene regulators. Cell Metab. 2013; 17(1):85-100. PMC: 3969420. DOI: 10.1016/j.cmet.2012.12.013. View

11.

Park J, Attardo G, Hansen I, Raikhel A . GATA factor translation is the final downstream step in the amino acid/target-of-rapamycin-mediated vitellogenin gene expression in the anautogenous mosquito Aedes aegypti. J Biol Chem. 2006; 281(16):11167-76. DOI: 10.1074/jbc.M601517200. View

12.

Mair W, Sgro C, Johnson A, Chapman T, Partridge L . Lifespan extension by dietary restriction in female Drosophila melanogaster is not caused by a reduction in vitellogenesis or ovarian activity. Exp Gerontol. 2004; 39(7):1011-9. DOI: 10.1016/j.exger.2004.03.018. View

13.

Solon-Biet S, McMahon A, Ballard J, Ruohonen K, Wu L, Cogger V . The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014; 19(3):418-30. PMC: 5087279. DOI: 10.1016/j.cmet.2014.02.009. View

14.

Bulow M, Aebersold R, Pankratz M, Junger M . The Drosophila FoxA ortholog Fork head regulates growth and gene expression downstream of Target of rapamycin. PLoS One. 2011; 5(12):e15171. PMC: 3013099. DOI: 10.1371/journal.pone.0015171. View

15.

Niccoli T, Partridge L . Ageing as a risk factor for disease. Curr Biol. 2012; 22(17):R741-52. DOI: 10.1016/j.cub.2012.07.024. View

16.

Lentjes M, Niessen H, Akiyama Y, de Bruine A, Melotte V, van Engeland M . The emerging role of GATA transcription factors in development and disease. Expert Rev Mol Med. 2016; 18:e3. PMC: 4836206. DOI: 10.1017/erm.2016.2. View

17.

Lossky M, Wensink P . Regulation of Drosophila yolk protein genes by an ovary-specific GATA factor. Mol Cell Biol. 1995; 15(12):6943-52. PMC: 230949. DOI: 10.1128/MCB.15.12.6943. View

18.

Taylor R, Dillin A . XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell. 2013; 153(7):1435-47. PMC: 4771415. DOI: 10.1016/j.cell.2013.05.042. View

19.

Le Couteur D, Solon-Biet S, Cogger V, Mitchell S, Senior A, de Cabo R . The impact of low-protein high-carbohydrate diets on aging and lifespan. Cell Mol Life Sci. 2016; 73(6):1237-52. PMC: 11108352. DOI: 10.1007/s00018-015-2120-y. View

20.

Robida-Stubbs S, Glover-Cutter K, Lamming D, Mizunuma M, Narasimhan S, Neumann-Haefelin E . TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab. 2012; 15(5):713-24. PMC: 3348514. DOI: 10.1016/j.cmet.2012.04.007. View