ITP1 compounds

Interventions Testing Program: Effects of various treatments on lifespan and related phenotypes in genetically heterogeneous mice (UM-HET3)   (2004-2023)

Miller RA, Strong R, Harrison DE, Rosenthal NA


Studied compounds:

(R/S)-1,3-butanediol: a ketogenic dietary supplement reported to increase survival and attenuate pathological as well as other age-associated traits and to ameliorate aging phenotypes of the brain and heart. [Wikipedia article]

17-a-estradiol: an isomer of 17-b-estradiol that has reduced affinity for the estrogen nuclear receptor; 17-a-estradiol was tested to determine if it would recapitulate the protective effects of 17-b-estradiol and increase lifespan. [Wikipedia article]

17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride: inhibits heat shock protein 90 (HSP90).

2-(2-Hydroxyphenyl)benzoxazole: a compound which acts as a multi-site proton acceptor as well as a proton donor, in addition to forming a strong intramolecular hydrogen bond.

3-(3-hydroxybenzyl)-5-methylbenzo[d]oxazol-2(3H)-one (MIF098): is a proinflammatory cytokine (macrophage migration inhibition factor (MIF)) antagonist proposed to decrease chronic inflammation and disease.

4-OH-a-phenyl-N-tert-butyl nitrone: is the 4-hydroxy derivative and principal metabolite of a-phenyl-N-tert-butyl nitrone (PBN), a commonly used free radical spin trap; PBN has reported pharmacologic activities in stroke and cancer.

Acarbose: an anti-diabetes drug that inhibits α-glucosidase, slowing carbohydrate breakdown. It was anticipated that it might act as a caloric restriction mimetic. [Wikipedia article]

Aspirin: a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, fever, or inflammation. [Wikipedia article]

b-guanidinopropionic acid: lowers both blood glucose and blood insulin.

Caffeic acid phenethyl ester: a compound reported to possess anti-oxidant, anti-inflammatory, and immunomodulatory capabilities, as well as specific toxicity to transformed and tumor cells. [Wikipedia article]

Canagliflozin: an FDA-approved diabetes drug that acts primarily by inhibition of the sodium glucose transporter 2 (SGLT2); can greatly reduce the risk of progression to kidney failure as well as the risk of cardiovascular events. [Wikipedia article]

Captopril: an FDA-approved angiotensin converting enzyme (ACE) inhibitor used for treatment of hypertension; reported to increase lifespan in C. elegans. [Wikipedia article]

Candesartan cilexetil: an angiotensin-receptor blocker which lowers blood pressure and improves cardiovascular function and insulin sensitivity in obese, hypertensive individuals. [Wikipedia article]

Curcumin: is the principal curcuminoid of turmeric, sold as an herbal supplement. [Wikipedia article]

Enalapril: a drug reported to improve hypertension, obesity, diabetes and congestive heart failure in aged humans and rodent models. [Wikipedia article]

Fish oil: a source of omega-3 fatty acids, which have anti-inflammatory properties and are thought to be protective for cardiovascular disease in some human studies. [Wikipedia article]

Geranylgeranyl acetone: induces heat shock protein (HSP70) in mammalian tissues; long-lived species, compared with related short-lived species within the same order, have elevated HSP levels.

Glycine: an amino acid; dietary glycine can block methionine toxicity; excess glycine might depress methionine levels and thus mimic some of the benefits of a low methionine diet which has been reported to extend median and maximum lifespan in rats. [Wikipedia article]

Green tea extract: includes polyphenols extracted from green tea; has anti-oxidant properties where some constituents scavenge reactive oxygen species. [Wikipedia article]

INT-767 FXR/TGR5 agonist: a bile acid analog which is a dual agonist of farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5 which has been shown to affect energy metabolism, glucose homeostasis, bile composition/secretion, and inflammation.

Inulin: a source of dietary fiber produced by many types of plants. [Wikipedia article]

L-Leucine: a branched chain amino acid reported to increase chronological lifespan in yeast and lengthen life in C. elegans and mice. [Wikipedia article]

Medium-chain triglyceride oil: a mixture of triglycerides composed of fatty acids with a chain length of 6-10 carbons; reported use for weight control. [Wikipedia article]

Metformin: an anti-diabetes drug that increases response to insulin in tissues. [Wikipedia article]

Metformin plus Rapamycin: the combination of metformin and rapamycin tested the hypothesis that addition of metformin would ameliorate some of the negative effects of rapamycin on glucose metabolism.

Methylene blue: an agent that increases in vitro fibroblast lifespan and increases activity of mitochondria complex IV; reported to protect against oxidative damage. [Wikipedia article]

Minocycline: antibiotic in the same class as tetracycline and doxycycline.

MitoQ: small anti-oxidant molecule (also known as Coenzyme Q10) that accumulates in mitochondria in cultured cells and in vivo.

Nicotinamide riboside: precursor to nicotinamide adenine dinucleotide reported to improve liver function, protect against diabetic neuropathy, protect against high-fat diet induced obesity, promote oxidative metabolism. [Wikipedia article]

Nitroflurbiprofen: is a nitric oxide-releasing flurbiprofen derivative and a nonsteroidal anti-inflammatory agent.

Nordihydroguaiaretic acid (NDGA): a potent antioxidant, anti-inflammatory molecule, NDGA was originally isolated from the creosote bush but is now chemically synthesized. [Wikipedia article]

Oxaloacetic acid: an intermediary in oxidative metabolism such as gluconeogenesis, urea cycle, glyoxylate cycle, amino acid synthesis, fatty acid synthesis and citric acid cycle. [Wikipedia article]

PB125: a formulation consisting of rosemary extract, ashwagandha extract, and luteolin reported to produce activation of nuclear factor erythroid 2-related factor 2 (Nrf2).

Protandim: a mixture of five botanical extracts designed to activate the Nrf2 (Nuclear factor erythroid 2-related factor 2) transcription factor, which mediates responses to oxidative and other forms of stress. [Wikipedia article]

Rapamycin: represses the mTOR complex, a key nutrient sensing pathway impacting protein synthesis. [Wikipedia article]

Resveratrol: a natural phenol and phytoalexin produced by several plants in response to injury; examples are skin of grapes, blueberries, raspberries, mulberries. [Wikipedia article]

Simvastatin: a lipid-lowering medication. [Wikipedia article]

Sulindac: an FDA-approved Non-Steroidal Anti-Inflammatory Drug (NSAID) with reported ability to initiate a preconditioning response that protects against oxidative damage; shown to protect against cardiac and brain ischemia-reperfusion damage and retinal epithelial cell degeneration. [Wikipedia article]

Syringaresinol: a component of the ginseng berry reported to extend lifespan of C. elegans and Drosophila; appears to act through FOXO3/sirtuin dependent mechanisms in C. elegans and inhibition of IGF-1 signaling in mammals. [Wikipedia article]

TM5441: an inhibitor of PAI-1, the primary inhibitor of tissue and urokinase plasminogen activators.

Ursodeoxycholic acid (UDCA): Bile acids, including UDCA, are products of cholesterol catabolism that activate xenobiotic detoxification pathways and are involved in regulatation of lipid, glucose and energy metabolism. [Wikipedia article]

Ursolic acid: present in many plants; reported to decrease d-galactose-induced neurotoxicity in mice; inhibit cognitive impairment induced by a high-fat diet; increase skeletal muscle mass and function while improving glucose tolerance and reducing obesity. [Wikipedia article]