| Investigators |
Richard A Miller University of Michigan, Ann Arbor, MI Randy Strong University of Texas Health Science Center, San Antonio, TX Ron Korstanje The Jackson Laboratory, Bar Harbor, ME David E Harrison The Jackson Laboratory, Bar Harbor, ME Nadia A Rosenthal The Jackson Laboratory, Bar Harbor, ME |
| Contact | Richard A Miller millerr@umich.edu
|
| Affiliated Center | National Institute on Aging Interventions Testing Program (ITP) |
| Acknowledgements | Funding provided by NIH AG022303, AG022307, AG022308, AG066346 |
| Phenotype archive study | |
| MPD identifiers | ITP1 MPD:508 |
| 5 updates/corrections. Initial release date: 08/2024. | |
|
Click above to copy-paste the entire citation for this MPD web page. |
| Compound name and |
Year cohort |
Dose in food | Age at initiation | Compound's effect on lifespan* |
Other phenotypes | Ref# |
|---|---|---|---|---|---|---|
| 16-a-hydroxyestriol |
C2020 | 5 ppm | 12 mo | males p = 0.0004 |
[19] | |
| 17-a-estradiol |
C2009 | 4.8 ppm | 10 mo | males p = 0.0025 |
[8] | |
| 17-a-estradiol |
C2011 | 14 ppm | 10 mo | males p < 0.0001 |
• body weight • uterus weight (OVX) |
[10] |
| 17-a-estradiol |
C2016 | 14.4 ppm | 16 or 20 mo | 16 mo males p < 0.0001 20 mo males p = 0.0064 |
• body weight |
[16] |
| 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride |
C2015 | 30 ppm | 6 mo | [14] | ||
| 2-(2-Hydroxyphenyl)benzoxazole |
C2012 | 1 ppm | 15 mo | [12] | ||
| 2,4-dinitrophenol |
C2020 | 3 ppm | 6 mo | [19] | ||
| 3-(3-hydroxybenzyl)-5-methylbenzo[d]oxazol-2(3H)-one |
C2016 | 240 ppm | 8 mo |
• body weight |
[16] | |
| 4-OH-a-phenyl-N-tert-butyl nitrone |
C2004 | 315 ppm | 4 mo | [2] | ||
| 4-phenylbutyrate |
C2019 | 1000 ppm | 9 mo | [18] | ||
| acarbose |
C2009 | 1000 ppm | 4 mo | males p < 0.0001 females p = 0.0048 |
[8] | |
| acarbose |
C2012 | 1000 ppm | 16 mo | males p < 0.0001 |
[10] | |
| acarbose |
C2013 | 400, 1000, 2500 ppm | 4 or 8 mo | 400 ppm females p = 0.033 400 ppm males p < 0.0001 1000 ppm females p = 0.0027 1000 ppm males p < 0.0001 2500 ppm females p = 0.0061 2500 ppm males p < 0.0001 |
• body composition • body weight • fat pads • grip strength • grip duration • pathology • postprandial glucose • rotarod |
[12] |
| a-Ketoglutarate |
C2020 | 20,000 ppm | 18 mo | [19] | ||
| aspirin |
C2004 | 20 ppm | 4 mo | males p = 0.0106 |
[2] | |
| aspirin |
C2014 | 60, 200 ppm | 11 mo | [13] | ||
| astaxanthin |
C2019 | 4000 ppm | 12 mo | males p = 0.003 |
[18] | |
| b-guanidinopropionic acid |
C2015 | 3300 ppm | 6 mo | [14] | ||
| caffeic acid phenethyl ester |
C2005 | 30 and 300 ppm | 4 mo | [4] | ||
| canagliflozin |
C2016 | 180 ppm | 7 mo | males p < 0.0001 |
• body weight |
[14] |
| canagliflozin |
C2020 | 180 ppm | 6 or 16 mo | males 6 mo p = 0.0209 males 16 mo p = 0.023 |
[19] | |
| candesartan cilexetil |
C2016 | 30 ppm | 7 mo |
• body weight |
[16] | |
| captopril |
C2017 | 180 ppm | 5 mo | females p = 0.002 males p = 0.001 |
[17] | |
| curcumin |
C2007 | 2000 ppm | 4 mo | [6] | ||
| dimethyl fumarate |
C2019 | 120 ppm | 9 or 16 mo | [18] | ||
| enalapril |
C2005 | 120 ppm | 4 mo | [4] | ||
| fisetin |
C2018 | 600 ppm | 20 mo (3 days on/11 days off) and 20 mo (continuous) | [18] | ||
| fish oil |
C2010 | 15,000 and 50,000 ppm | 9 mo |
• body weight |
[10] | |
| geranylgeranyl acetone |
C2016 | 600 ppm | 9 mo |
• body weight |
[16] | |
| glycine |
C2014 | 80,000 ppm | 9 mo | females p = 0.0167 males p = 0.0024 |
[13] | |
| green tea extract |
C2007 | 2000 ppm | 4 mo | [6] | ||
| Hydralazine |
C2020 | 30 ppm | 6 or 16 mo | [19] | ||
| INT-767 FXR/TGR5 agonist |
C2012 | 180 ppm | 10 mo | [12] | ||
| inulin |
C2014 | 600 ppm | 11 mo | [13] | ||
| L-leucine |
C2017 | 40,000 ppm | 5 mo | [17] | ||
| meclizine |
C2019 | 800 ppm | 12 mo | males p = 0.027 |
[18] | |
| medium-chain triglyceride oil |
C2007 | 60,000 ppm | 4 mo | [6] | ||
| metformin |
C2011 | 1000 ppm | 9 mo |
• body weight |
[10] | |
| metformin and rapamycin |
C2011 | Met:1000 ppm and Rapa:14 ppm | 9 mo | both sexes p < 0.0001 |
• body weight |
[10] |
| methylene blue |
C2009 | 28 ppm | 4 mo | [8] | ||
| minocycline |
C2015 | 300 ppm | 6 mo | [14] | ||
| MitoQ |
C2015 | 100 ppm | 7 mo | [14] | ||
| mycophenolic acid |
C2019 | 6.7 ppm | 9 mo | [18] | ||
| Nebivolol |
C2020 | 60 ppm | 6 mo | [19] | ||
| nicotinamide riboside |
C2016 | 1000 ppm | 8 mo |
• body weight |
[16] | |
| nitroflurbiprofen |
C2004 | 200 ppm | 4 mo | [2] | ||
| nordihydroguaiaretic acid |
C2004 | 2500 ppm | 9 mo | males p = 0.0006 |
[2] | |
| nordihydroguaiaretic acid |
C2010 | 800, 2500, 5000 ppm | 6 mo | 800 ppm males p = 0.0228 2500 ppm males p = 0.0147 5000 ppm males p = 0.0028 |
• body weight • grip strength • grip duration • rotarod |
[10] |
| oxaloacetic acid |
C2007 | 2200 ppm | 4 mo | [6] | ||
| PB125 |
C2017 | see publication | 5 mo | [17] | ||
| Protandim |
C2011 | 600 ppm then 1200 ppm | 10 mo then 17 mo | males p = 0.0095 |
• body weight |
[10] |
| rapamycin |
C2005 | 14 ppm | 20 mo | both sexes p < 0.0001 |
[4] | |
| rapamycin |
C2006 | 14 ppm | 9 mo | both sexes p < 0.0001 |
[5] | |
| rapamycin |
C2009 | 4.7, 14, and 42 ppm | 9 mo | 4.7 ppm females p < 0.0001 14 ppm females p < 0.0001 14 ppm males p = 0.0034 42 ppm both sexes p < 0.0001 |
[7] | |
| rapamycin |
C2015 | 42 ppm | 20 mo (stop at 23) | males p = 0.0243 |
[15] | |
| rapamycin |
C2015 | 42 ppm | 20 mo (but every other month) | females = 0.0001 males p = 0.0019 |
[15] | |
| rapamycin |
C2015 | 42 ppm | 20 mo | females p < 0.0001 males p = 0.0007 |
[15] | |
| rapamycin and acarbose |
C2017 | Rapa: 14.7 ppm and ACA: 1000 ppm | 9 or 16 mo | 9 mo females p < 0.0001 9 mo males p < 0.0001 16 mo females p < 0.0001 16 mo males p < 0.0001 |
[17] | |
| resveratrol |
C2006 | 300 and 1200 ppm | 12 mo | [5] | ||
| resveratrol |
C2007 | 300 ppm | 4 mo | [6] | ||
| (R/S)-1,3-butanediol |
C2017 | 100,000 ppm | 6 mo | females p = 0.0395 |
[17] | |
| SG1002 |
C2018 | 240 ppm | 18 mo | [18] | ||
| SG1002 |
C2019 | 240 ppm | 6 mo | [18] | ||
| simvastatin |
C2006 | 12 and 120 ppm | 10 mo | [5] | ||
| Sodium thiosulfate |
C2020 | 10,000 ppm | 6 mo | [19] | ||
| sulindac |
C2017 | 5 ppm | 5 mo | [17] | ||
| syringaresinol |
C2017 | 300 ppm | 5 mo | [17] | ||
| TM5441 |
C2014 | 60 ppm | 11 mo | [13] | ||
| ursodeoxycholic acid |
C2011 | 5000 ppm | 5 mo |
• body weight |
[10] | |
| ursolic acid |
C2013 | 2000 ppm | 10 mo | [12] |
* Log-rank test p-value on treated vs. control, shown when p ≤ 0.05 for each sex separately. Statistical definitions
1. Miller RA, Harrison DE, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA, Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Strong R. An Aging Interventions Testing Program: study design and interim report.
Aging Cell. 2007 Aug;6(4):565-75. Epub 2007 Jun 18.
2. Strong R, Miller RA, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA, Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Harrison DE. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.
Aging Cell. 2008 Oct;7(5):641-50. doi: 10.1111/j.1474-9726.2008.00414.x.
3. Nadon NL, Strong R, Miller RA, Nelson J, Javors M, Sharp ZD, Peralba JM, Harrison DE. Design of aging intervention studies: the NIA interventions testing program.
Age (Dordr). 2008 Dec;30(4):187-99. doi: 10.1007/s11357-008-9048-Epub 2008 Apr 18.
4. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
Nature. 2009 Jul 16;460(7253):392-5. doi: 10.1038/nature0822Epub 2009 Jul 8.
5. Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, Strong R. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice.
J Gerontol A Biol Sci Med Sci. 2011 Feb;66(2):191-20doi: 10.1093/gerona/glq178. Epub 2010 Oct 25.
6. Strong R, Miller RA, Astle CM, Baur JA, de Cabo R, Fernandez E, Guo W, Javors M, Kirkland JL, Nelson JF, Sinclair DA, Teter B, Williams D, Zaveri N, Nadon NL, Harrison DE. Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice.
J Gerontol A Biol Sci Med Sci. 2013 Jan;68(1):6-16. doi: 10.1093/gerona/gls070. Epub 2012 Mar 26.
7. Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, Hejtmancik JF, Nadon N, Strong R, Wood LK, Woodward MA, Miller RA. Rapamycin slows aging in mice.
Aging Cell. 2012 Aug;11(4):675-82. doi: 10.1111/j.1474-9726.2012.00832.x. Epub 2012 Jun 4.
8. Harrison DE, Strong R, Allison DB, Ames BN, Astle CM, Atamna H, Fernandez E, Flurkey K, Javors MA, Nadon NL, Nelson JF, Pletcher S, Simpkins JW, Smith D, Wilkinson JE, Miller RA. Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males.
Aging Cell. 2014 Apr;13(2):273-82. doi: 10.1111/acel.12170. Epub 2013 Nov 19.
9. Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors MA, Li X, Nadon NL, Nelson JF, Pletcher S, Salmon AB, Sharp ZD, Van Roekel S, Winkleman L, Strong R. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction.
Aging Cell. 2014 Jun;13(3):468-77. doi: 10.1111/acel.12194. Epub 2014 Feb 9.
10. Strong R, Miller RA, Antebi A, Astle CM, Bogue M, Denzel MS, Fernandez E, Flurkey K, Hamilton KL, Lamming DW, Javors MA, de Magalhães JP, Martinez PA, McCord JM, Miller BF, Müller M, Nelson JF, et al. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer.
Aging Cell. 2016 Oct;15(5):872-84. doi: 10.1111/acel.12496. Epub 2016 Jun 16.
11. Nadon NL, Strong R, Miller RA, Harrison DE. NIA Interventions Testing Program: Investigating Putative Aging Intervention Agents in a Genetically Heterogeneous Mouse Model.
EBioMedicine. 2017 Jul;21:3-4. doi: 10.1016/j.ebiom.2016.11.038. Epub 2016 Dec 2.
12. Harrison DE, Strong R, Alavez S, Astle CM, DiGiovanni J, Fernandez E, Flurkey K, Garratt M, Gelfond JAL, Javors MA, Levi M, Lithgow GJ, Macchiarini F, Nelson JF, Sukoff Rizzo SJ, Slaga TJ, Stearns T, Wilkinson JE, Miller RA. Acarbose improves health and lifespan in aging HET3 mice.
Aging Cell. 2019 Apr;18(2):e12898. doi: 10.1111/acel.12898. Epub 2019 Jan 27.
13. Miller RA, Harrison DE, Astle CM, Bogue MA, Brind J, Fernandez E, Flurkey K, Javors M, Ladiges W, Leeuwenburgh C, Macchiarini F, Nelson J, Ryazanov AG, Snyder J, Stearns TM, Vaughan DE, Strong R. Glycine supplementation extends lifespan of male and female mice.
Aging Cell. 2019 Jun;18(3):e12953. doi: 10.1111/acel.12953. Epub 2019 Mar 27.
14. Miller RA, Harrison DE, Allison DB, Bogue M, Debarba L, Diaz V, Fernandez E, Galecki A, Garvey WT, Jayarathne H, Kumar N, Javors MA, Ladiges WC, Macchiarini F, Nelson J, Reifsnyder P, Rosenthal NA, Sadagurski M, Salmon AB, Smith DL Jr, Snyder JM, Lombard DB, Strong R. Canagliflozin extends life span in genetically heterogeneous male but not female mice.
JCI Insight. pii: 140019. doi: 10.1172/jci.insight.140019.
15. Strong R, Miller RA, Bogue M, Fernandez E, Javors MA, Libert S, Marinez PA, Murphy MP, Musi N, Nelson JF, Petrascheck M, Reifsnyder P, Richardson A, Salmon AB, Macchiarini F, Harrison DE. Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects.
Aging Cell. 2020 Nov;19(11):e13269. doi: 10.1111/acel.13269. Epub 2020 Nov 4.
16. Harrison DE, Strong R, Reifsnyder P, Kumar N, Fernandez E, Flurkey K, Javors MA, Lopez-Cruzan M, Macchiarini F, Nelson JF, Bitto A, Sindler AL, Cortopassi G, Kavanagh K, Leng L, Bucala R, Rosenthal N, Salmon A, Stearns TM, Bogue M, Miller RA. 17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex.
Aging Cell. 2021 May;20(5):e13328. doi: 10.1111/acel.13328. Epub 2021 Mar 31.
17. Strong R, Miller RA, Cheng CJ, Nelson JF, Gelfond J, Allani SK, Diaz V, Dorigatti AO, Dorigatti J, Fernandez E, Galecki A, Ginsburg B, Hamilton KL, Javors MA, Kornfeld K, Kaeberlein M, Kumar S, Lombard DB, Lopez-Cruzan M, Miller BF, Rabinovitch P, Reifsnyder P, Rosenthal NA, Bogue MA, Salmon AB, Suh Y, Verdin E, Weissbach H, Newman J, Maccchiarini F, Harrison DE. Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice.
Aging Cell. doi: 10.1111/acel.13724.
18. Harrison DE, Strong R, Reifsnyder P, Rosenthal N, Korstanje R, Fernandez E, Flurkey K, Ginsburg BC, Murrell MD, Javors MA, Lopez-Cruzan M, Nelson JF, Willcox BJ, Allsopp R, Watumull DM, Watumull DG, Cortopassi G, Kirkland JL, Tchkonia T, Choi YG, Yousefzadeh MJ, Robbins PD, Mitchell JR, Acar M, Sarnoski EA, Bene MR, Salmon A, Kumar N, Miller RA. Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used.
Geroscience. 2024 Feb;46(1):795-816. doi: 10.1007/s11357-023-01011-0. Epub 2023 Dec 2.
19. Miller RA, Harrison DE, Cortopassi GA, Dehghan I, Fernandez E, Garratt M, Geisler JG, Ginsburg BC, Han ML, Kaczorowski CC, Kumar N, Leiser SF, Lopez-Cruzan M, Milne G, Mitchell JR, Nelson JF, Reifsnyder PC, Salmon AB, Korstanje R, Rosenthal N, Strong R. Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin.
Geroscience. 2024 Oct;46(5):4657-4670. doi: 10.1007/s11357-024-01176-2. Epub 2024 May 16.