KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Chemicals, Peptides, and Recombinant Proteins
Rapamycin	LC Laboratories	Cat#R-5000
Protandim	LifeVantage Corporation	https://www.lifevantage.com/
17-alpha-estradiol	Steraloids Inc.	Cat#E0870-000
Acarbose	Spectrum Chemical Mfg. Corp.	Cat#A3965
Ascorbyl-palmitate	MedChemExpress	Cat#HY-B0987
KU-0063794	MedChemExpress	Cat#HY-50710
AZD8055	MedChemExpress	Cat#HY-10422
Rilmenidine	AK Scientific, Inc.	Cat#H733
Critical Commercial Assays
PureLink RNA Mini Kit	Thermo Fisher Scientific	Cat#12183020
Deposited Data
Raw and mapped RNAseq data	This paper	GEO: GSE131901
Raw and preprocessed metabolome data (batch 1)	This paper	Data S1
Additional metabolome data (batch 2)	Ma et al., 2015	N/A
App for visualization of associations between gene expression response and longevity: GENtervention	This paper	http://gladyshevlab.org/GENtervention/
Database of genes regulating lifespan: GenAge	De Magalhães and Toussaint, 2004	http://genomics.senescence.info/genes/
Public data on gene expression in response to lifespan-extending interventions	Amador-Noguez et al., 2004; Selman et al., 2009; Amador-Noguez et al., 2005; Selman et al., 2006; Tsuchiya et al., 2004; Pearson et al., 2008; Dhahbi et al., 2005; Streeper et al., 2012; Boylston et al., 2006; Zhou et al., 2012; Zhang et al., 2012; Martin-Montalvo et al., 2013; Fok et al., 2014b; Mercken et al., 2014a; Fok et al., 2014a; Collino et al., 2013; Sun et al., 2013; Hofmann et al., 2015; Rusli et al., 2015; Edwards et al., 2007; Mitchell et al., 2016; Rowland et al., 2005; Soo et al., 2015; Barger et al., 2017; Barger et al., 2008	ArrayExpress: E-MEXP-153, E-MEXP-2320, E-MEXP-347, E-MEXP-748. GEO: GSE1093, GSE11291, GSE11845, GSE2431, GSE26267, GSE3129, GSE3150, GSE36838, GSE39313, GSE40936, GSE40977, GSE46895, GSE48331, GSE48333, GSE49000, GSE50789, GSE51108, GSE55272, GSE60596, GSE61233, GSE6323, GSE70857, GSE75574, GSE81959 and GSE988
Public data on gene expression in response to interventions for association test	Ramadoss et al., 2010; Alonso et al., 2017; Baze et al., 2010b; Osburn et al., 2008; Mercken et al., 2014b; Kautz et al., 2008; Rhoads et al., 2018; Kanfi et al., 2012	GEO: GSE21060, GSE77082, GSE15891, GSE11287, GSE49000, GSE10421 and GSE104234
Experimental Models: Organisms/Strains
Mouse: C57BL/6J	The Jackson Laboratory	JAX 000664
Mouse: UM-HET3	Laboratory of Richard Miller (Miller et al., 2007)	N/A
Mouse: GHRKO ([C57BL/6J × BALB/cByJ]/F2)	Laboratory of Richard Miller (Coschigano et al., 2003)	N/A
Mouse: Snell dwarf mice ([DW/J × C3H/HEJ]/F2)	Laboratory of Richard Miller (Flurkey et al., 2001)	N/A
Software and Algorithms
Mapping reads: STAR 2.5.2b	Dobin et al., 2013	https://github.com/alexdobin/STAR/releases
Counting reads: featureCounts 1.5	Liao et al., 2014	http://subread.sourceforge.net/
Adaptor removing: Trimmomatic	Bolger et al., 2014	http://www.usadellab.org/cms/index.php?page=trimmomatic
Functional enrichment: GSEA	Subramanian et al., 2005	http://software.broadinstitute.org/gsea/index.jsp
App development: shiny	Chang et al., 2016	https://shiny.rstudio.com/
Programming environment: RStudio	https://www.rstudio.com/	N/A
Enrichment by transcriptional factors: TRANSFAC	Matys, 2006	http://genexplain.com/transfac/
Network visualization: Cytoscape	Shannon et al., 2003	https://cytoscape.org/
Functional annotation: DAVID	Huang et al., 2009a, 2009b	https://david.ncifcrf.gov/
Differential gene expression analysis of RNAseq: edgeR	Robinson et al., 2009	https://bioconductor.org/packages/release/bioc/html/edgeR.html
Differential gene expression analysis of microarrays: limma	Ritchie et al., 2015	https://bioconductor.org/packages/release/bioc/html/limma.html
Mixed-effect model: metafor	Viechtbauer, 2010	http://CRAN.R-project.org/package=metafor
RNAseq normalization: RLE	Anders and Huber, 2010	https://bioconductor.org/packages/release/bioc/html/edgeR.html
Prediction of compounds with similar gene expression response: CMap	Lamb et al., 2006; Subramanian et al., 2017	https://clue.io