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
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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
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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
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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
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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
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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
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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
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Glycine |
Methionine restriction mimetic |
• Increases lifespan in flies and in rats. |
Sugiyama et al., 1987; Orentreich et al., 1993; ;Obata and Miura, 2015
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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
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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
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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
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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
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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
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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
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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
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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
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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
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