Table 2.

Compounds under testing in the NIA-ITP with no data reported to date.

Compound	Classification/ Properties	Primary and secondary effects	Reference
1,3-Butanediol	Precursor of the ketone body β-hydroxybutyrate (β-HB)	• Ketogenic diets increase levels of β-HB and have been shown to improve healthspan, memory, and longevity in mice	Newman et al., 2017; Roberts et al., 2017
17-DMAG	Derivative of the benzoquinone ansamycin antibiotic geldanamycin	• Inhibitor of the ATPase function of HSP90 with anti-inflammatory properties in autoimmune and neurodegenerative diseases, as well as obesity and metabolic diseases. • Prolongevity effects via reduction of acetyl-CoA levels with concomitant stimulation of autophagy.	Calamini and Morimoto, 2012; Tukaj and Węgrzyn (2016); Verma et al., 2016; Ambade et al., 2014; Madeo et al., 2014
2-(2-hydroxyphenyl)-benzoxazole (HBX)	Metal chelator and anti-aggregation properties	• Increases lifespan in C. elegans. • Increases lifespan in ALS mouse model.	Alavez et al., 2011; Evans et al., 2016
β-guanidinopropionic acid (β-GPA)	Analogue of creatine that competitively inhibits creatine kinase and depletes intracellular phosphocreatine and ATP levels	• Activates AMPK and promotes mitochondrial biogenesis in skeletal muscle in rats. • Extends lifespan in flies via AMPK.	Oudman et al., 2013; Reznick et al., 2007; Yang et al., 2015
Bile acids	Steroid acids	• Dietary absorption of lipids and the fat-soluble vitamins A, D, E and K. • Activation of nuclear hormone receptors, mainly the farnesoid X receptor (FXR), controlling hepatic lipid and glucose metabolism. • Activation of G protein-coupled receptor TGR5, acting on the immune system response, energy expenditure, glucose homeostasis, and insulin sensitivity. • Extends yeast chronological lifespan in a TOR-independent manner (lithocholic acid). • Modulates lifespan in C. elegans through nuclear receptor signaling (dafrachronic acid).	Russell, 2009; Trauner et al., 2010; Pols et al., 2011; Rizzo et al., 2010; Watanabe et al., 2012; Goldberg et al., 2010; Beach et al., 2013, 2015; Gerisch et al., 2007; Magner et al., 2013; Amador-Noguez et al., 2007
Canagliflozin	Sodium-glucose co-transporter-2 (SGLT2) inhibitor convoluted tubule of the kidney, thereby facilitating the excretion of glucose in the urine. • Caloric restriction mimetic.	• Blocks the reabsorption of glucose in the proximal	Kalra, 2014; Kalra et al., 2016
Candesartan cilexetil	Prodrug form of candesartan, an angiotensin II receptor antagonist	• Increases the lifespan of spontaneously hypertensive rats.	Baiardi et al., 2004
Captopril	Angiotensin-converting enzyme (ACE) inhibitor	• Extends lifespan in nematodes via a mechanism that is distinct from calorie restriction.	Kumar et al., 2016
Geranylgeranylacetone (GGA)	Inducer of the 70-kDa heat shock protein (HSP70)	• Prevents hearing loss and hair cell death in a mouse model of age-related hearing loss. Positive effects on cognition and Aβ pathology in the APP23 mouse model of Alzheimer’s disease.	Hirakawa et al., 1996; Hoshino et al., 2013
Glycine	Methionine restriction mimetic	• Increases lifespan in flies and in rats.	Sugiyama et al., 1987; Orentreich et al., 1993; ;Obata and Miura, 2015
Inulin	Bifidogenic and fiber-like compound	• Regulates GLP-1 and ghrelin levels for the control of food intake and appetite, stimulates the immune system, improves mineral absorption and bone mineralization, influences blood and liver lipid metabolism. • Reduces the risk of chronic gastrointestinal track and colon cancer. • Increases lifespan in rats. • Increase muscle strength in humans. • Anti-inflammatory effects via gut microbiota.	Milani et al., 2016; Tuohy, 2007; Shoaib et al., 2016; Rozan et al., 2008; Buigues et al., 2016
L-Leucine	Branched chain amino acid (BCAAs)	• Extends lifespan in yeast, nematodes, and mice. • Stimulates protein synthesis in skeletal muscle via mTOR pathway. • Increases functional performance and lean tissue mass in elderly humans.	Alvers et al., 2009; D’Antona et al., 2010; Mansfeld et al., 2015; Norton and Layman, 2006; Ispoglou et al., 2016
Minocycline	Semi-synthetic, second-generation tetracycline analogue	•Antioxidant properties, anti-inflammatory/immunomodulatory effects, and neuroprotection mainly by inhibition of microglia activation and attenuation of apoptosis. • Inhibits the formation of kynurenine from tryptophan, mechanism implicated in age-related metabolic disorders as well as psychiatric disorders • Improves healthspan and lifespan in Drosophila.	Garrido-Mesa et al., 2013; Oxenkrug et al., 2012; Oxenkrug, 2013; Mora et al., 2013
MitoQ	Antioxidant ubiquinone conjugated to a lipophilic cation with anti-apoptotic effects	• Delays the onset of paralysis and increase lifespan in C. elegans model of AD.; • Increases lifespan in flies. • Increases lifespan in ALS mouse model.	Kelso et al., 2001; Ng et al., 2014; Magwere et al., 2006; Miquel et al., 2014
MIF098	Interferes with the ability of macrophage migration inhibitory factor (MIF) cytokine to bind to its receptor, CD74	• Inhibition of MIF extends lifespan in mice. • Anti-inflammatory effects.	Harper et al., 2010; Weiser et al., 2015; Hare et al., 2010
Nicotinamide riboside	NAD+ precursor	• Extends lifespan by increasing NAD + synthesis in yeast.	Belenky et al., 2007
PB125	Phytochemical compound consisting of carnosol, carnosic acid, shogaol, gingerol, luteolin, and withaferin A	• Activates NRF2 pathway in mice and cells.	Hybertson and McCord, 2017 (patent)
SG1002 (sodium polysulthionate)	Prodrug of the endogenous signaling gasotransmitter hydrogen sulfide (H2S)	• Increases lifespan in a Sir2-dependent manner in C. elegans. • Prevent oxidative stress and activates sirtuins affecting nutrient-sensing pathways.	Polhemus et al., 2015; Miller and Roth, 2007; Ng et al., 2018
Sulindac	Nonsteroidal anti-inflammatory drug (NSAID) that inhibits both cyclooxygenase I and II	• Inhibit tumorigenesis, and might prevent sporadic colorectal adenomas in patients with a history of resected adenomas. • Attenuates age-related deficits in learning and memory in aged Fischer 344 rats. • Might extend lifespan in yeast, nematodes and flies (similar to ibuprofen).	Meyskens et al., 2008; Gurpinar et al., 2014; Mesches et al., 2004; He et al., 2014
Syringaresinol	Phytochemical compound found in Panax ginseng berries	• Activate Sirt1 gene expression in human umbilical vein endothelial cells and delay senescence in a FOXO3-dependent manner. • Modulates gut integrity, microbiota diversity, and delays age-associated immunosenescence. • Induces vasorelaxation in endothelial cells by increasing nitric oxide production.	Cho et al., 2013, 2016; Chung et al., 2012
TM5441	Senolytic drug via plasminogen activator inhibitor-1 (PAI-1)	• Increases lifespan in the Klotho-deficient mice. • Protection against high-fat diet-induced obesity and insulin resistance.	Boe et al., 2013; Jeong et al., 2016; Piao et al., 2016; Eren et al., 2014;
Ursolic acid	Pentacyclic triterpenoid	• Increases lifespan in C. elegans. • Increases skeletal muscle mass in human and mouse • Reduces adiposity (mouse). • Stimulates IGF-1/ AKT signaling.	Vayndorf et al., 2013; Kunkel et al., 2011, 2012