A toolbox for the longitudinal assessment of healthspan in aging mice

被引:87
作者
Bellantuono, I. [1 ,2 ]
de Cabo, R. [3 ]
Ehninger, D. [4 ]
Di Germanio, C. [3 ]
Lawrie, A. [5 ]
Miller, J. [6 ]
Mitchell, S. J. [7 ]
Navas-Enamorado, I. [3 ]
Potter, P. K. [8 ]
Tchkonia, T. [6 ]
Trejo, J. L. [9 ]
Lamming, D. W. [10 ,11 ]
机构
[1] Univ Sheffield, Hlth Lifespan Inst, Dept Oncol & Metab, Sheffield, S Yorkshire, England
[2] Univ Sheffield, MRC Arthrit Res UK Ctr Integrated Res Musculoskel, Sheffield, S Yorkshire, England
[3] NIH, Translat Gerontol Branch, Baltimore, MD USA
[4] German Ctr Neurodegenerat Dis DZNE, Venusberg Campus 1, Bonn, Germany
[5] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England
[6] Mayo Clin, Robert & Arlene KogodCtr Aging, Rochester, MN USA
[7] Harvard TH Chan Sch Publ Hlth, Dept Mol Med, Boston, MA USA
[8] Oxford Brookes Univ, Dept Biol & Life Sci, Fac Hlth & Life Sci, Oxford, Oxon, England
[9] CSIC, Cajal Inst, Dept Translat Neurosci, Madrid, Spain
[10] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA
[11] Univ Wisconsin, Dept Med, Madison, WI 53706 USA
基金
欧盟地平线“2020”;
关键词
EXTENDS LIFE-SPAN; OBJECT RECOGNITION; COGNITIVE IMPAIRMENT; MOUSE MODEL; DECREASED CONSUMPTION; GLUCOSE-HOMEOSTASIS; CALORIC RESTRICTION; CELLULAR SENESCENCE; RAPAMYCIN TREATMENT; DIASTOLIC FUNCTION;
D O I
10.1038/s41596-019-0256-1
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The number of people aged over 65 is expected to double in the next 30 years. For many, living longer will mean spending more years with the burdens of chronic diseases such as Alzheimer's disease, cardiovascular disease, and diabetes. Although researchers have made rapid progress in developing geroprotective interventions that target mechanisms of aging and delay or prevent the onset of multiple concurrent age-related diseases, a lack of standardized techniques to assess healthspan in preclinical murine studies has resulted in reduced reproducibility and slow progress. To overcome this, major centers in Europe and the United States skilled in healthspan analysis came together to agree on a toolbox of techniques that can be used to consistently assess the healthspan of mice. Here, we describe the agreed toolbox, which contains protocols for echocardiography, novel object recognition, grip strength, rotarod, glucose tolerance test (GTT) and insulin tolerance test (ITT), body composition, and energy expenditure. The protocols can be performed longitudinally in the same mouse over a period of 4-6 weeks to test how candidate geroprotectors affect cardiac, cognitive, neuromuscular, and metabolic health. A series of techniques (echocardiography, novel object recognition, grip strength, rotarod, glucose and insulin tolerance tests, body composition, and energy expenditure) are used to assess the health of mice.
引用
收藏
页码:540 / 574
页数:35
相关论文
共 134 条
  • [1] Health benefits of late-onset metformin treatment every other week in mice
    Alfaras I.
    Mitchell S.J.
    Mora H.
    Lugo D.R.
    Warren A.
    Navas-Enamorado I.
    Hoffmann V.
    Hine C.
    Mitchell J.R.
    Le Couteur D.G.
    Cogger V.C.
    Bernier M.
    de Cabo R.
    [J]. npj Aging and Mechanisms of Disease, 3 (1)
  • [2] Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice
    Allard, Joanne S.
    Perez, Evelyn J.
    Fukui, Koji
    Carpenter, Priscilla
    Ingram, Donald K.
    de Cabo, Rafael
    [J]. BEHAVIOURAL BRAIN RESEARCH, 2016, 301 : 1 - 9
  • [3] Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice
    Apelo, Sebastian I. Arriola
    Pumper, Cassidy P.
    Baar, Emma L.
    Cummings, Nicole E.
    Lamming, Dudley W.
    [J]. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2016, 71 (07): : 876 - 881
  • [4] Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system
    Apelo, Sebastian I. Arriola
    Neuman, Joshua C.
    Baar, Emma L.
    Syed, Faizan A.
    Cummings, Nicole E.
    Brar, Harpreet K.
    Pumper, Cassidy P.
    Kimple, Michelle E.
    Lamming, Dudley W.
    [J]. AGING CELL, 2016, 15 (01) : 28 - 38
  • [5] Resveratrol improves health and survival of mice on a high-calorie diet
    Baur, Joseph A.
    Pearson, Kevin J.
    Price, Nathan L.
    Jamieson, Hamish A.
    Lerin, Carles
    Kalra, Avash
    Prabhu, Vinayakumar V.
    Allard, Joanne S.
    Lopez-Lluch, Guillermo
    Lewis, Kaitlyn
    Pistell, Paul J.
    Poosala, Suresh
    Becker, Kevin G.
    Boss, Olivier
    Gwinn, Dana
    Wang, Mingyi
    Ramaswamy, Sharan
    Fishbein, Kenneth W.
    Spencer, Richard G.
    Lakatta, Edward G.
    Le Couteur, David
    Shaw, Reuben J.
    Navas, Placido
    Puigserver, Pere
    Ingram, Donald K.
    de Cabo, Rafael
    Sinclair, David A.
    [J]. NATURE, 2006, 444 (7117) : 337 - 342
  • [6] Find drugs that delay many diseases of old age
    Bellantuono, Ilaria
    [J]. NATURE, 2018, 554 (7692) : 293 - 295
  • [7] Object recognition analysis in mice using nose-point digital video tracking
    Benice, T. S.
    Raber, Jacob
    [J]. JOURNAL OF NEUROSCIENCE METHODS, 2008, 168 (02) : 422 - 430
  • [8] Sex differences in object recognition are modulated by object similarity
    Bettis, Tania
    Jacobs, Lucia F.
    [J]. BEHAVIOURAL BRAIN RESEARCH, 2012, 233 (02) : 288 - 292
  • [9] Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice
    Bitto, Alessandro
    Ito, Takashi K.
    Pineda, Victor V.
    LeTexier, Nicolas J.
    Huang, Heather Z.
    Sutlief, Elissa
    Tung, Herman
    Vizzini, Nicholas
    Chen, Belle
    Smith, Kaleb
    Meza, Daniel
    Yajima, Masanao
    Beyer, Richard P.
    Kerr, Kathleen F.
    Davis, Daniel J.
    Gillespie, Catherine H.
    Snyder, Jessica M.
    Treuting, Piper M.
    Kaeberlein, Matt
    [J]. ELIFE, 2016, 5
  • [10] Accessing Data Resources in the Mouse Phenome Database for Genetic Analysis of Murine Life Span and Health Span
    Bogue, Molly A.
    Peters, Luanne L.
    Paigen, Beverly
    Korstanje, Ron
    Yuan, Rong
    Ackert-Bicknell, Cheryl
    Grubb, Stephen C.
    Churchill, Gary A.
    Chesler, Elissa J.
    [J]. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2016, 71 (02): : 170 - 177