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The dog aging project: translational geroscience in companion animals

Mammalian Genome volume 27, pages 279–288 (2016)Cite this article

Abstract

Studies of the basic biology of aging have identified several genetic and pharmacological interventions that appear to modulate the rate of aging in laboratory model organisms, but a barrier to further progress has been the challenge of moving beyond these laboratory discoveries to impact health and quality of life for people. The domestic dog, Canis familiaris, offers a unique opportunity for surmounting this barrier in the near future. In particular, companion dogs share our environment and play an important role in improving the quality of life for millions of people. Here, we present a rationale for increasing the role of companion dogs as an animal model for both basic and clinical geroscience and describe complementary approaches and ongoing projects aimed at achieving this goal.

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References

  • Anisimov VN (2013) Metformin: do we finally have an anti-aging drug? Cell Cycle 12:3483–3489

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Anisimov VN, Egormin PA, Piskunova TS, Popovich IG, Tyndyk ML, Yurova MN, Zabezhinski MA, Anikin IV, Karkach AS, Romanyukha AA (2010) Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle 9:188–197

    CAS  Article  PubMed  Google Scholar 

  • Anisimov VN, Berstein LM, Popovich IG, Zabezhinski MA, Egormin PA, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Kovalenko IG, Poroshina TE (2011a) If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging (Albany NY) 3:148–157

    CAS  Article  Google Scholar 

  • Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Rosenfeld SV, Blagosklonny MV (2011b) Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle 10:4230–4236

    CAS  Article  PubMed  Google Scholar 

  • Augustine JJ, Bodziak KA, Hricik DE (2007) Use of sirolimus in solid organ transplantation. Drugs 67:369–391

    CAS  Article  PubMed  Google Scholar 

  • Bannister CA, Holden SE, Jenkins-Jones S, Morgan CL, Halcox JP, Schernthaner G, Mukherjee J, Currie CJ (2014) Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab 16:1165–1173

    CAS  Article  PubMed  Google Scholar 

  • Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342

    CAS  Article  PubMed  Google Scholar 

  • Bonnett BN, Egenvall A, Hedhammar A, Olson P (2005) Mortality in over 350,000 insured Swedish dogs from 1995–2000: I. Breed-, gender-, age- and cause-specific rates. Acta Vet Scand 46:105–120

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Burch JB, Augustine AD, Frieden LA, Hadley E, Howcroft TK, Johnson R, Khalsa PS, Kohanski RA, Li XL, Macchiarini F, Niederehe G, Oh YS, Pawlyk AC, Rodriguez H, Rowland JH, Shen GL, Sierra F, Wise BC (2014) Advances in geroscience: impact on healthspan and chronic disease. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S1–S3

    Article  PubMed  PubMed Central  Google Scholar 

  • Check Hayden E (2014) Pet dogs set to test anti-ageing drug. Nature 514:546

    CAS  Article  PubMed  Google Scholar 

  • Check Hayden E (2015) Anti-ageing pill pushed as bona fide drug. Nature 522:265–266

    CAS  Article  PubMed  Google Scholar 

  • Chen C, Liu Y, Zheng P (2009) mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2:ra75

    PubMed  PubMed Central  Google Scholar 

  • Creevy KE, Austad SN, Hoffman JM, O’Neill DG, Promislow DE (2016) The companion dog as a model for the longevity dividend. Cold Spring Harb Perspect Med 6:a026633

    Article  PubMed  Google Scholar 

  • Dai DF, Karunadharma PP, Chiao YA, Basisty N, Crispin D, Hsieh EJ, Chen T, Gu H, Djukovic D, Raftery D, Beyer RP, MacCoss MJ, Rabinovitch PS (2014) Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart. Aging Cell 13:529–539

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • de Oliveira MA, Martins EMF, Wang Q, Sonis S, Demetri G, George S, Butrynski J, Treister NS (2011) Clinical presentation and management of mTOR inhibitor-associated stomatitis. Oral Oncol 47:998–1003

    Article  PubMed  Google Scholar 

  • DiNicolantonio JJ, Bhutani J, O’Keefe JH (2015) Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes. Open Heart 2:e000327

    Article  PubMed  PubMed Central  Google Scholar 

  • Egenvall A, Bonnett BN, Hedhammar A, Olson P (2005) Mortality in over 350,000 insured Swedish dogs from 1995–2000: II. Breed-specific age and survival patterns and relative risk for causes of death. Acta Vet Scand 46:121–136

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Ferrucci L (2008) The Baltimore longitudinal study of aging (BLSA): a 50-year-long journey and plans for the future. J Gerontol A Biol Sci Med Sci 63:1416–1419

    Article  PubMed  Google Scholar 

  • Fleming JM, Creevy KE, Promislow DE (2011) Mortality in north american dogs from 1984 to 2004: an investigation into age-, size-, and breed-related causes of death. J Vet Intern Med 25:187–198

    CAS  Article  PubMed  Google Scholar 

  • Flynn JM, O’Leary MN, Zambataro CA, Academia EC, Presley MP, Garrett BJ, Zykovich A, Mooney SD, Strong R, Rosen CJ, Kapahi P, Nelson MD, Kennedy BK, Melov S (2013) Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell 12:851–862

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Fontana L, Meyer TE, Klein S, Holloszy JO (2004) Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A 101:6659–6663

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B (2014) Metformin: from mechanisms of action to therapies. Cell Metab 20:953–966

    CAS  Article  PubMed  Google Scholar 

  • Freeman LM (2012) Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats. Journal of veterinary internal medicine/American College of Veterinary Internal Medicine 26:3–17

    CAS  Article  PubMed  Google Scholar 

  • Gilmore KM, Greer KA (2015) Why is the dog an ideal model for aging research? Exp Gerontol 71:14–20

    Article  PubMed  Google Scholar 

  • Goldman DP, Cutler D, Rowe JW, Michaud PC, Sullivan J, Peneva D, Olshansky SJ (2013) Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Aff 32:1698–1705

    Article  Google Scholar 

  • Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA (2013) Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155:1624–1638

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Gordon I, Paoloni M, Mazcko C, Khanna C (2009) The Comparative Oncology Trials Consortium: using spontaneously occurring cancers in dogs to inform the cancer drug development pathway. PLoS Med 6:e1000161

    Article  PubMed  PubMed Central  Google Scholar 

  • Greeley EH, Spitznagel E, Lawler DF, Kealy RD, Segre M (2006) Modulation of canine immunosenescence by life-long caloric restriction. Vet Immunol Immunopathol 111:287–299

    CAS  Article  PubMed  Google Scholar 

  • Greer KA, Canterberry SC, Murphy KE (2007) Statistical analysis regarding the effects of height and weight on life span of the domestic dog. Res Vet Sci 82:208–214

    Article  PubMed  Google Scholar 

  • Guy MK, Page RL, Jensen WA, Olson PN, Haworth JD, Searfoss EE, Brown DE (2015) The Golden Retriever Lifetime Study: establishing an observational cohort study with translational relevance for human health. Philos Trans R Soc Lond B Biol Sci 370:20140230

    Article  PubMed  PubMed Central  Google Scholar 

  • Halloran J, Hussong SA, Burbank R, Podlutskaya N, Fischer KE, Sloane LB, Austad SN, Strong R, Richardson A, Hart MJ, Galvan V (2012) Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience 223:102–113

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • 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 (2014) Acarbose, 17-alpha-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell 13:273–282

    CAS  Article  PubMed  Google Scholar 

  • He K, Shi JC, Mao XM (2014) Safety and efficacy of acarbose in the treatment of diabetes in Chinese patients. Ther Clin Risk Manag 10:505–511

    CAS  PubMed  PubMed Central  Google Scholar 

  • Holloszy JO, Fontana L (2007) Caloric restriction in humans. Exp Gerontol 42:709–712

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493:338–345

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Johnson SC, Sangesland M, Kaeberlein M, Rabinovitch PS (2015) Modulating mTOR in aging and health. Interdisciplinary topics in gerontology 40:107–127

    Article  PubMed  Google Scholar 

  • Kaeberlein M (2013) Longevity and aging. F1000prime reports 5(5)

  • Kaeberlein M (2013b) mTOR inhibition: from aging to autism and beyond. Scientifica (Cairo) 2013:849186

    Google Scholar 

  • Kaeberlein M (2014) Rapamycin and ageing: when, for how long, and how much? J Genet Genomics 41:459–463

    Article  PubMed  PubMed Central  Google Scholar 

  • Kaeberlein M (2015) The Biology of Aging: Citizen Scientists and their pets as a bridge between research on model organisms and human subjects. Vet Pathol 53:291–298

    Article  PubMed  Google Scholar 

  • Kaeberlein M, Rabinovitch PS, Martin GM (2015) Healthy aging: the ultimate preventative medicine. Science 350:1191–1193

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Kealy RD, Lawler DE, Ballam JM, Mantz SL, Biery DN, Greeley EH, Lust G, Segre M, Smith GK, Stowe HD (2002) Effects of diet restriction on life span and age-related changes in dogs. J Am Vet Med Assoc 220:1315–1320

    Article  PubMed  Google Scholar 

  • Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE, Rando TA, Richardson A, Schadt EE, Wyss-Coray T, Sierra F (2014) Geroscience: linking aging to chronic disease. Cell 159:709–713

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Kraus C, Pavard S, Promislow DE (2013) The size-life span trade-off decomposed: why large dogs die young. Am Nat 181:492–505

    Article  PubMed  Google Scholar 

  • Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA (2012) Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335:1638–1643

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Larson G, Karlsson EK, Perri A, Webster MT, Ho SY, Peters J, Stahl PW, Piper PJ, Lingaas F, Fredholm M, Comstock KE, Modiano JF, Schelling C, Agoulnik AI, Leegwater PA, Dobney K, Vigne JD, Vila C, Andersson L, Lindblad-Toh K (2012) Rethinking dog domestication by integrating genetics, archeology, and biogeography. Proc Natl Acad Sci U S A 109:8878–8883

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Larson JC, Allstadt SD, Fan TM, Khanna C, Lunghofer PJ, Hansen RJ, Gustafson DL, Legendre AM, Galyon GD, LeBlanc AK, Martin-Jimenez T (2016) Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs. Am J Vet Res 77:65–71

    Article  PubMed  Google Scholar 

  • Lawler DF, Ballam JM, Meadows R, Larson BT, Li Q, Stowe HD, Kealy RD (2007) Influence of lifetime food restriction on physiological variables in Labrador retriever dogs. Exp Gerontol 42:204–214

    CAS  Article  PubMed  Google Scholar 

  • Lin AL, Zheng W, Halloran JJ, Burbank RR, Hussong SA, Hart MJ, Javors M, Shih YY, Muir E, Solano Fonseca R, Strong R, Richardson AG, Lechleiter JD, Fox PT, Galvan V (2013) Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer’s disease. J Cereb Blood Flow Metab 33:1412–1421

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Majumder S, Caccamo A, Medina DX, Benavides AD, Javors MA, Kraig E, Strong R, Richardson A, Oddo S (2012) Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1beta and enhancing NMDA signaling. Aging Cell 11:326–335

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Mannick JB, Del Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, Lonetto MA, Maecker HT, Kovarik J, Carson S, Glass DJ, Klickstein LB (2014) mTOR inhibition improves immune function in the elderly. Sci Transl Med 6:268ra179

    Article  PubMed  Google Scholar 

  • Marsden CD, Ortega-Del Vecchyo D, O’Brien DP, Taylor JF, Ramirez O, Vila C, Marques-Bonet T, Schnabel RD, Wayne RK, Lohmueller KE (2016) Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs. Proc Natl Acad Sci U S A 113:152–157

    CAS  Article  PubMed  Google Scholar 

  • Martin GM, LaMarco K, Strauss E, Kelner KL (2003) Research on aging: the end of the beginning. Science 299:1339–1341

    CAS  Article  PubMed  Google Scholar 

  • Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin MJ, Schwab M, Pollak M, Zhang Y, Yu Y, Becker KG, Bohr VA, Ingram DK, Sinclair DA, Wolf NS, Spindler SR, Bernier M, de Cabo R (2013) Metformin improves healthspan and lifespan in mice. Nat commun 4:2192

    Article  PubMed  PubMed Central  Google Scholar 

  • Masoro EJ (2005) Overview of caloric restriction and ageing. Mech Ageing Dev 126:913–922

    CAS  Article  PubMed  Google Scholar 

  • Mercken EM, Mitchell SJ, Martin-Montalvo A, Minor RK, Almeida M, Gomes AP, Scheibye-Knudsen M, Palacios HH, Licata JJ, Zhang Y, Becker KG, Khraiwesh H, Gonzalez-Reyes JA, Villalba JM, Baur JA, Elliott P, Westphal C, Vlasuk GP, Ellis JL, Sinclair DA, Bernier M, de Cabo R (2014) SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell 13:787–796

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • 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 (2011) Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 66:191–201

    Article  PubMed  Google Scholar 

  • Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G, Minor RK, Vlasuk GP, Ellis JL, Sinclair DA, Dawson J, Allison DB, Zhang Y, Becker KG, Bernier M, de Cabo R (2014) The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet. Cell Rep 6:836–843

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Mulvey L, Sinclair A, Selman C (2014) Lifespan modulation in mice and the confounding effects of genetic background. J Genet Genomics 41:497–503

    Article  PubMed  PubMed Central  Google Scholar 

  • Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schroder S, Adler T, Afonso LC, Aguilar-Pimentel JA, Becker L, Garrett L, Hans W, Hettich MM, Holtmeier R, Holter SM, Moreth K, Prehn C, Puk O, Racz I, Rathkolb B, Rozman J, Naton B, Ordemann R, Adamski J, Beckers J, Bekeredjian R, Busch DH, Ehninger G, Graw J, Hofler H, Klingenspor M, Klopstock T, Ollert M, Stypmann J, Wolf E, Wurst W, Zimmer A, Fuchs H, Gailus-Durner V, Hrabe de Angelis M, Ehninger D (2013) Rapamycin extends murine lifespan but has limited effects on aging. J Clin Investig 123:3272–3291

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Nelson RW (2000) Oral medications for treating diabetes mellitus in dogs and cats. J Small Anim Pract 41:486–490

    CAS  Article  PubMed  Google Scholar 

  • Nelson RW, Reusch CE (2014) Animal models of disease: classification and etiology of diabetes in dogs and cats. J Endocrinol 222:T1–T9

    CAS  Article  PubMed  Google Scholar 

  • Paoloni M, Khanna C (2008) Translation of new cancer treatments from pet dogs to humans. Nat Rev Cancer 8:147–156

    CAS  Article  PubMed  Google Scholar 

  • Paoloni MC, Mazcko C, Fox E, Fan T, Lana S, Kisseberth W, Vail DM, Nuckolls K, Osborne T, Yalkowsy S, Gustafson D, Yu Y, Cao L, Khanna C (2010) Rapamycin pharmacokinetic and pharmacodynamic relationships in osteosarcoma: a comparative oncology study in dogs. PLoS One 5:e11013

    Article  PubMed  PubMed Central  Google Scholar 

  • Parks RJ, Fares E, Macdonald JK, Ernst MC, Sinal CJ, Rockwood K, Howlett SE (2012) A procedure for creating a frailty index based on deficit accumulation in aging mice. J Gerontol A Biol Sci Med Sci 67:217–227

    Article  PubMed  Google Scholar 

  • Pitt JN, Kaeberlein M (2015) Why is aging conserved and what can we do about it? PLoS Biol 13:e1002131

  • Popovich IG, Anisimov VN, Zabezhinski MA, Semenchenko AV, Tyndyk ML, Yurova MN, Blagosklonny MV (2014) Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin. Cancer Biol Ther 15:586–592

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Proschowsky HF, Rugbjerg H, Ersboll AK (2003) Mortality of purebred and mixed-breed dogs in Denmark. Prev Vet Med 58:63–74

    Article  PubMed  Google Scholar 

  • Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, Roberts SB, Group CS (2015) A 2-year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity. J Gerontol A Biol Sci Med Sci 70:1097–1104

    Article  PubMed  Google Scholar 

  • Richards SE, Wang Y, Claus SP, Lawler D, Kochhar S, Holmes E, Nicholson JK (2013) Metabolic phenotype modulation by caloric restriction in a lifelong dog study. J Proteome Res 12:3117–3127

    CAS  Article  PubMed  Google Scholar 

  • Richardson A, Fischer KE, Speakman JR, de Cabo R, Mitchell SJ, Peterson CA, Rabinovitch P, Chiao YA, Taffet G, Miller RA, Renteria RC, Bower J, Ingram DK, Ladiges WC, Ikeno Y, Sierra F, Austad SN (2016) Measures of healthspan as indices of aging in mice-a recommendation. J Gerontol A Biol Sci Med Sci 71:427–430

    Article  PubMed  Google Scholar 

  • Rochon J, Bales CW, Ravussin E, Redman LM, Holloszy JO, Racette SB, Roberts SB, Das SK, Romashkan S, Galan KM, Hadley EC, Kraus WE, Group CS (2011) Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy. J Gerontol A Biol Sci Med Sci 66:97–108

    Google Scholar 

  • Sasaki H, Asanuma H, Fujita M, Takahama H, Wakeno M, Ito S, Ogai A, Asakura M, Kim J, Minamino T, Takashima S, Sanada S, Sugimachi M, Komamura K, Mochizuki N, Kitakaze M (2009) Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase. Circulation 119:2568–2577

    CAS  Article  PubMed  Google Scholar 

  • Savolainen P, Zhang YP, Luo J, Lundeberg J, Leitner T (2002) Genetic evidence for an East Asian origin of domestic dogs. Science 298:1610–1613

    CAS  Article  PubMed  Google Scholar 

  • Schoenebeck JJ, Ostrander EA (2014) Insights into morphology and disease from the dog genome project. Annu Rev Cell Dev Biol 30:535–560

    CAS  Article  PubMed  Google Scholar 

  • Shannon LM, Boyko RH, Castelhano M, Corey E, Hayward JJ, McLean C, White ME, Abi Said M, Anita BA, Bondjengo NI, Calero J, Galov A, Hedimbi M, Imam B, Khalap R, Lally D, Masta A, Oliveira KC, Perez L, Randall J, Tam NM, Trujillo-Cornejo FJ, Valeriano C, Sutter NB, Todhunter RJ, Bustamante CD, Boyko AR (2015) Genetic structure in village dogs reveals a Central Asian domestication origin. Proc Natl Acad Sci U S A 112:13639–13644

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Syrjanen KJ (1980) Spleen white pulp morphology as an indicator of the immunological state in DBA/2 mice bearing mastocytoma. Exp Pathol (Jena) 18:223–231

    CAS  Google Scholar 

  • Thamm DH, Vail DM (2015) Veterinary oncology clinical trials: design and implementation. Vet J 205:226–232

    Article  PubMed  Google Scholar 

  • Tsao CW, Vasan RS (2015) Cohort Profile: The Framingham Heart Study (FHS): overview of milestones in cardiovascular epidemiology. Int J Epidemiol 44:1800–1813

    Article  PubMed  Google Scholar 

  • Urfer SR, Greer K, Wolf NS (2011) Age-related cataract in dogs: a biomarker for life span and its relation to body size. Age (Dordr) 33:451–460

    Article  Google Scholar 

  • Vite CH, Head E (2014) Aging in the canine and feline brain. Vet Clin North Am Small Anim Pract 44:1113–1129

    Article  PubMed  PubMed Central  Google Scholar 

  • Weindruch R, Walford RL, Fligiel S, Guthrie D (1986) The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr 116:641–654

    CAS  PubMed  Google Scholar 

  • Wess G, Schulze A, Butz V, Simak J, Killich M, Keller LJ, Maeurer J, Hartmann K (2010) Prevalence of dilated cardiomyopathy in Doberman Pinschers in various age groups. J Vet Intern Med 24:533–538

    CAS  Article  PubMed  Google Scholar 

  • Yi H, Brooks ED, Thurberg BL, Fyfe JC, Kishnani PS, Sun B (2014) Correction of glycogen storage disease type III with rapamycin in a canine model. J Mol Med 92:641–650

    CAS  Article  PubMed  Google Scholar 

  • Zhang Y, Bokov A, Gelfond J, Soto V, Ikeno Y, Hubbard G, Diaz V, Sloane L, Maslin K, Treaster S, Rendon S, van Remmen H, Ward W, Javors M, Richardson A, Austad SN, Fischer K (2014) Rapamycin extends life and health in C57BL/6 mice. J Gerontol A Biol Sci Med Sci 69:119–130

    CAS  Article  PubMed  Google Scholar 

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Acknowledgments

This work is supported by a grant from the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging (NIH P30AG013280) to MK and NIH Grant R24AG044284 to DP and KC.

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Authors and Affiliations

  1. Department of Pathology, University of Washington, Seattle, WA, USA

    Matt Kaeberlein & Daniel E. L. Promislow

  2. Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA

    Kate E. Creevy

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  1. Matt Kaeberlein
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  3. Daniel E. L. Promislow
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Correspondence to Matt Kaeberlein.

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Kaeberlein, M., Creevy, K.E. & Promislow, D.E.L. The dog aging project: translational geroscience in companion animals. Mamm Genome 27, 279–288 (2016). https://doi.org/10.1007/s00335-016-9638-7

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Keywords

  • Metformin
  • Rapamycin
  • Healthy Aging
  • Rapamycin Treatment
  • Impaired Glucose Homeostasis