High Intensity Interval Training Improves Physical Performance and Frailty in Aged Mice

Seldeen, Kenneth Ladd; Lasky, Ginger; Leiker, Merced Marie; Pang, Manhui; Personius, Kirkwood Ely; Troen, Bruce Robert

doi:10.1093/gerona/glx120

Cited by 104Frailty in Older AdultsNutrition and Health in AgingCardiovascular and exercise physiology

High Intensity Interval Training Improves Physical Performance and Frailty in Aged Mice

Seldeen, Kenneth Ladd, Lasky, Ginger, Leiker, Merced Marie, Pang, Manhui, Personius, Kirkwood Ely, Troen, Bruce Robert·2018·The Journals of Gerontology Series A

DOI 10.1093/gerona/glx120

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Abstract

Sarcopenia and frailty are highly prevalent in older individuals, increasing the risk of disability and loss of independence. High intensity interval training (HIIT) may provide a robust intervention for both sarcopenia and frailty by achieving both strength and endurance benefits with lower time commitments than other exercise regimens. To better understand the impacts of HIIT during aging, we compared 24-month-old C57BL/6J sedentary mice with those that were administered 10-minute uphill treadmill HIIT sessions three times per week over 16 weeks. Baseline and end point assessments included body composition, physical performance, and frailty based on criteria from the Fried physical frailty scale. HIIT-trained mice demonstrated dramatic improvement in grip strength (HIIT 10.9% vs -3.9% in sedentary mice), treadmill endurance (32.6% vs -2.0%), and gait speed (107.0% vs 39.0%). Muscles from HIIT mice also exhibited greater mass, larger fiber size, and an increase in mitochondrial biomass. Furthermore, HIIT exercise led to a dramatic reduction in frailty scores in five of six mice that were frail or prefrail at baseline, with four ultimately becoming nonfrail. The uphill treadmill HIIT exercise sessions were well tolerated by aged mice and led to performance gains, improvement in underlying muscle physiology, and reduction in frailty.

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High-intensity interval training in mice improved grip strength, treadmill endurance, and gait speed, and increased muscle mass, muscle fiber size, and mitochondrial biomass.
“those undergoing 10-min uphill treadmill, high-intensity interval training (HIIT) sessions over 16 weeks showed significant improvements in grip strength, treadmill endurance, and gait speed, and exhibited increased muscle mass, larger muscle fiber size, and greater mitochondrial biomass [19].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [19]

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Kim, Y. J., Kim, H. J., Lee, W. J., & Seong, J. K. (2020) · Laboratory Animal Research · doi:10.1186/s42826-019-0035-8 · Cited by 64 · see citing works
Animal Models of Exercise From Rodents to Pythons
Hastings, M. H., Herrera, J. J., Guseh, J. S., Atlason, B. A., Houstis, N. E., Kadir, A. A., Li, H., Sheffield, C., Singh, A. P., Roh, J. D., et al. (2022) · Circulation Research · doi:10.1161/circresaha.122.320247 · Cited by 55 · see citing works
Measuring Exercise Capacity and Physical Function in Adult and Older Mice
Graber, T. G., Maroto, R., Fry, C. S., Brightwell, C. R., & Rasmussen, B. B. (2020) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaa205 · Cited by 54 · see citing works
“CFAB is loosely based upon the FIAV, which was designed to detect changes in frailty status, based on the reverse translation of the Fried Frailty Phenotype (5,6,18).”
BackgroundMethod
Geroprotectors: A role in the treatment of frailty
Trendelenburg, A., Scheuren, A. C., Potter, P. K., Müller, R., & Bellantuono, I. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.03.002 · Cited by 50 · see citing works
Exercise and Exercise Mimetics for the Treatment of Musculoskeletal Disorders
Cento, A. S., Leigheb, M., Caretti, G., & Penna, F. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00739-6 · Cited by 49 · see citing works
Effects of high-intensity interval training on mitochondrial supercomplex assembly and biogenesis, mitophagy, and the AMP-activated protein kinase pathway in the soleus muscle of aged female rats
Han, C., Lu, P., & Yan, S.-Z. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111648 · Cited by 44 · see citing works
Muscle-Specific Cellular and Molecular Adaptations to Late-Life Voluntary Concurrent Exercise
Dungan, C. M., Brightwell, C. R., Wen, Y., Zdunek, C. J., Latham, C. M., Thomas, N. T., Zagzoog, A. M., Brightwell, B. D., Nolt, G. L., Keeble, A. R., et al. (2022) · Function · doi:10.1093/function/zqac027 · Cited by 41 · see citing works
Making Mice Mighty: recent advances in translational models of load-induced muscle hypertrophy
Murach, K. A., McCarthy, J. J., Peterson, C. A., & Dungan, C. M. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00319.2020 · Cited by 43 · see citing works
Gut microbiota metabolism of branched‐chain amino acids and their metabolites can improve the physiological function of aging mice
Wang, H., Feng, L., Pei, Z., Zhao, J., Lu, S., & Lu, W. (2024) · Aging Cell · doi:10.1111/acel.14434 · Cited by 38 · see citing works
“The mouse grip strength test was carried out according to the method described by Seldeen et al. (Seldeen et al., 2018 ) using a grip strength meter (Jinan Yiyan Technology Co., LTD).”
Frailty and cytokines in preclinical models: Comparisons with humans
Heinze-Milne, S., Banga, S., & Howlett, S. E. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111706 · Cited by 38 · see citing works
Physiological Systems in Promoting Frailty
Perazza, L. R., Brown‐Borg, H. M., & Thompson, L. V. (2022) · Comprehensive physiology · doi:10.1002/cphy.c210034 · Cited by 64 · see citing works
Identifying Characteristics of Frailty in Female Mice Using a Phenotype Assessment Tool
Kwak, D., Baumann, C. W., & Thompson, L. V. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz092 · Cited by 36 · see citing works
“These two clinical assessment tools were successfully reverse-translated for preclinical animal models with the overreaching goal to tease out the biological features associated with frailty status and diminished physical resilience (13,20).”
BackgroundMethod
Proteomics-based identification of different training adaptations of aged skeletal muscle following long-term high-intensity interval and moderate-intensity continuous training in aged rats
Li, F., Sun, L., Wu, D.-S., Gao, H.-E., & Zhu, M. (2019) · Aging · doi:10.18632/aging.102044 · Cited by 35 · see citing works
“Further details on these tests are reported previously [5, 6].”
Background
Myeloid-Derived Suppressor Cells at the Intersection of Inflammaging and Bone Fragility
Kirkwood, K. L., Zhang, L., Thiyagarajan, R., Seldeen, K. L., & Troen, B. R. (2018) · Immunological Investigations · doi:10.1080/08820139.2018.1552360 · Cited by 36 · see citing works
Vitamin D Insufficiency Reduces Grip Strength, Grip Endurance and Increases Frailty in Aged C57Bl/6J Mice
Seldeen, K. L., Berman, R. N., Pang, M., Lasky, G., Weiss, C., MacDonald, B. A., Thiyagarajan, R., Redae, Y. Z., & Troen, B. R. (2020) · Nutrients · doi:10.3390/nu12103005 · Cited by 33 · see citing works
“This notion of a “training effect” is supported by significant declines in performance being observed in only 2 of our 8 assessments (speed sprint and open field activity monitoring, Figures 3E and 4C,D, respectively), which is generally uncharacteristic for what we and others have reported in mice aging from 24 to 28…”
Frailty and biological age. Which best describes our aging and longevity?
Félix, J., de Toda, I. M., Cerro, E. D., González-Sánchez, M., & la Fuente, M. D. (2024) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2024.101291 · Cited by 35 · see citing works
Mouse models of accelerated aging in musculoskeletal research for assessing frailty, sarcopenia, and osteoporosis – A review
Yilmaz, D., Mathavan, N., Wehrle, E., Kuhn, G. A., & Müller, R. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102118 · Cited by 34 · see citing works
“Another noteworthy example is the use of high-intensity interval training (HIIT) performed for 10 min, three times a week, over 8-16 weeks, which significantly improved physical performance and reduced frailty in aging male mice (Seldeen et al., 2018).”
High intensity interval training improves physical performance in aged female mice: A comparison of mouse frailty assessment tools
Seldeen, K. L., Redae, Y. Z., Thiyagarajan, R., Berman, R. N., Leiker, M. M., & Troen, B. R. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.04.001 · Cited by 32 · see citing works
Rodent models of frailty and their application in preclinical research
Banga, S., Heinze-Milne, S., & Howlett, S. E. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.01.008 · Cited by 31 · see citing works
Physiological Systems in Promoting Frailty
Perazza, L. R., Brown‐Borg, H. M., & Thompson, L. V. (2022) · Comprehensive physiology · doi:10.1002/j.2040-4603.2022.tb00224.x · Cited by 30 · see citing works
High Intensity Interval Training: A Potential Method for Treating Sarcopenia
Liu, Q., Xie, W., Luo, Y., Li, Y., Huang, W., Wu, Y., & Li, Y. (2022) · Clinical Interventions in Aging · doi:10.2147/cia.s366245 · Cited by 29 · see citing works
“and muscle mass in frail aged mice.(73,74) Some studies showed that elder people received HIIT protocol were observed to”
Background
Short-term nicotinamide riboside treatment improves muscle quality and function in mice and increases cellular energetics and differentiating capacity of myogenic progenitors
Seldeen, K. L., Shahini, A., Thiyagarajan, R., Redae, Y. Z., Leiker, M. M., Rajabian, N., Dynka, A., Andreadis, S. T., & Troen, B. R. (2021) · Nutrition · doi:10.1016/j.nut.2021.111189 · Cited by 24 · see citing works
Making More of IT: Enabling Intensive Motor Cognitive Rehabilitation Exercises in Geriatrics Using Information Technology Solutions
McCaskey, M. A., Schättin, A., Martin‐Niedecken, A. L., & de Bruin, E. D. (2018) · BioMed Research International · doi:10.1155/2018/4856146 · Cited by 25 · see citing works
Reversal of age-associated frailty by controlled physical exercise: The pre-clinical and clinical evidences
Arc‐Chagnaud, C., Millán-Domingo, F., Salvador‐Pascual, A., Correas, Á. G., González, G. O., la Rosa, A. D., Carretero, A., Gomez-Cabrera, M. C., & Viña, J. (2019) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2019.08.007 · Cited by 23 · see citing works
Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis
Wang, J., Jia, D., Zhang, Z., & Wang, D. (2025) · Metabolites · doi:10.3390/metabo15010059 · Cited by 23 · see citing works
Phenotypic Frailty Assessment in Mice: Development, Discoveries, and Experimental Considerations
Baumann, C. W., Kwak, D., & Thompson, L. V. (2020) · Physiology · doi:10.1152/physiol.00016.2020 · Cited by 21 · see citing works
Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice
Seldeen, K. L., Pang, M., Leiker, M. M., Bard, J., Rodríguez‐Gonzalez, M., Hernandez, M., Sheridan, Z., Nowak, N. J., & Troen, B. R. (2018) · Aging · doi:10.18632/aging.101471 · Cited by 22 · see citing works
“Mitochondrial activity was assessed as described previously [72].”
Method
Monitoring and Intervention Technologies to Manage Diabetic Older Persons: The CAPACITY Case—A Pilot Study
Pérez‐Rodríguez, R., Guevara-Guevara, T., Moreno-Sánchez, P. A., Villalba‐Mora, E., Valdés-Aragonés, M., Oviedo-Briones, M., Carnicero, J. A. C., & Rodríguez‐Mañas, L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00300 · Cited by 21 · see citing works
Aerobic Exercise Attenuates Frailty in Aging Male and Female C57Bl/6 Mice and Effects Systemic Cytokines Differentially by Sex
Bisset, E. S., Heinze-Milne, S., Grandy, S. A., & Howlett, S. E. (2021) · The Journals of Gerontology Series A · doi:10.1093/gerona/glab297 · Cited by 21 · see citing works
High Intensity Interval Training (HIIT) as a Potential Countermeasure for Phenotypic Characteristics of Sarcopenia: A Scoping Review
Hayes, L. D., Elliott, B., Yasar, Z., Bampouras, T. M., Sculthorpe, N. F., Sanal‐Hayes, N. E. M., & Hurst, C. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.715044 · Cited by 20 · see citing works
“, fat free mass [FFM], lean body mass) in adults diagnosed with sarcopenia, or oldest old humans, despite emerging evidence in the rodent model (Seldeen et al., 2018).”
Background
Aging-related limit of exercise efficacy on motor decline
Arnold, J. C., Cantu, M. A., Kasanga, E. A., Nejtek, V. A., Papa, E. V., Bugnariu, N., & Salvatore, M. F. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188538 · Cited by 16 · see citing works
A Comprehensive Review of Essential Aspects of Molecular Pathophysiological Mechanisms with Emerging Interventions for Sarcopenia in Older People
Prajapati, P., Kumar, A., Chaudary, R., Mangrulkar, S. V., Arya, M., & Kushwaha, S. (2023) · Current Molecular Pharmacology · doi:10.2174/1874467216666230308142137 · Cited by 17 · see citing works
The effect of gradual ovarian failure on dynamic muscle function and the role of high-intensity interval training on mitigating impairments
Hubbard, E. F., Mashouri, P., Pyle, W. G., & Power, G. A. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00318.2023 · Cited by 15 · see citing works
The utility of the rodent synergist ablation model in identifying molecular and cellular mechanisms of skeletal muscle hypertrophy
Burke, B. I., Ismaeel, A., & McCarthy, J. J. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00362.2024 · Cited by 15 · see citing works
Short Session High Intensity Interval Training and Treadmill Assessment in Aged Mice
Seldeen, K. L., Redae, Y. Z., Thiyagarajan, R., Berman, R. N., Leiker, M. M., & Troen, B. R. (2019) · Journal of Visualized Experiments · doi:10.3791/59138 · Cited by 16 · see citing works
Usability, user experience, and acceptance evaluation of CAPACITY: a technological ecosystem for remote follow-up of frailty
Pérez-Rodríguez, R., Villalba-Mora, E., Valdés-Aragonés, M., Ferre, X., Moral, C., Mas-Romero, M., Abizanda-Soler, P., & Rodríguez-Mañas, L. (2021) · Sensors · doi:10.3390/s21196458 · Cited by 13 · see citing works
Exerkines and myokines in aging sarcopenia
Wang, H., He, W., Chen, P., Wang, H., Wang, H., Zhu, L., & Liu, X. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1592491 · Cited by 14 · see citing works
“HIIT also enhances locomotor performance in aged mice, which includes muscle mass and strength, grip strength, and mitochondrial biomass (195).”
Effects of Different Types of Mechanical Loading on Trabecular Bone Microarchitecture in Rats
Ju, Y.-I., & Sone, T. (2021) · Journal of Bone Metabolism · doi:10.11005/jbm.2021.28.4.253 · Cited by 13 · see citing works
Feasibility of simple exercise interventions for men with osteoporosis – A prospective randomized controlled pilot study
Genest, F., Lindström, S., Scherer, S., Schneider, M. H., & Seefried, L. (2021) · Bone Reports · doi:10.1016/j.bonr.2021.101099 · Cited by 12 · see citing works
“Concurrently, growing scientific data propose exercise interventions as effective measures to mitigate or even partially reverse this age associated decay and prevent adverse outcomes (Nawrat-Szoltysik et al., 2018; Wisdom et al., 2015; Cesari et al., 2015; Cadore et al., 2014; Chen et al., 2018; Moore et al., 2018; S…”
Background
A recommended amount of hydrolyzed protein improves physiological function by regulating gut microbiota in aged mice
Wang, X., Lu, S., Fang, Z., Wang, H., Zhu, J., Zhao, J., Zhang, H., Hong, K., Lu, W., & Chen, W. (2022) · Food Research International · doi:10.1016/j.foodres.2022.110970 · Cited by 12 · see citing works
Comprehensive longitudinal non-invasive quantification of healthspan and frailty in a large cohort (n = 546) of geriatric C57BL/6 J mice
Marcozzi, S., Bigossi, G., Giuliani, M. E., Giacconi, R., Cardelli, M., Piacenza, F., Orlando, F., Segala, A., Valerio, A., Nisoli, E., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00737-1 · Cited by 12 · see citing works
“…weakness, poor endurance/exhaustion, slowness, and low activity); the identification of a specific cutoff point for each criterion [6–8, 28, 39] allows to categorize an animal as frail if at least three criteria are below the established cutoff point, pre-frail if one or two frailty…”
BackgroundMethod
Frailty in rodents: Models, underlying mechanisms, and management
Liu, P., Li, Y., & Ma, L. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101659 · Cited by 12 · see citing works
Exercise, Exerkines, and Sarcopenia
Chung, H. S., & Choi, K. M. (2026) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0972 · Cited by 12 · see citing works
“High-intensity interval training (HIIT) augments mitochondrial biomass and muscle mass, improves grip strength, and increases treadmill endurance and gait speed in aged mice [59].”
Preclinical Studies on the Effects of Frailty in the Aging Heart
Rose, R. A., & Howlett, S. E. (2024) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2024.03.003 · Cited by 10 · see citing works
Exploring the Potential of Treating Sarcopenia through Dietary Interventions
Srivastava, S., Pandey, V. K., Singh, A. K., & Dar, A. H. (2024) · Journal of Food Biochemistry · doi:10.1155/2024/3018760 · Cited by 10 · see citing works
CC002/Unc females are mouse models of exercise-induced paradoxical fat response
McMullan, R., Ferris, M. T., Bell, T. A., Menachery, V. D., Baric, R. S., Hua, K., Pomp, D., Smith‐Ryan, A. E., & de Villena, F. P. (2018) · Physiological Reports · doi:10.14814/phy2.13716 · Cited by 10 · see citing works
Cardioprotective effects of high‐intensity interval training are mediated through microRNA regulation of mitochondrial and oxidative stress pathways
Jeremic, N. S., Weber, G. J., Theilen, N. T., & Tyagi, S. C. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29409 · Cited by 10 · see citing works
“Furthermore, studies reveal HIIT increases muscle cross‐ sectional area (Blue, Smith‐Ryan, Trexler, & Hirsch, 2017), reduce frailty, and leads to dramatic physical performance gains (Seldeen et al., 2017).”
Background
High-Intensity Interval Training Combined with Glycine Supplementation Drives Ferroptosis Resistance to Counteract Skeletal Muscle Atrophy in Aging Mice
Ni, P., JIA, M.-M., He, J., YU, Z., & Li, F. (2025) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003722 · Cited by 9 · see citing works
Klotho regulates the myogenic response of muscle to mechanical loading and exercise
Ochi, E., Barrington, A., Wehling‐Henricks, M., Avila, M. H., Kuro‐o, M., & Tidball, J. G. (2023) · Experimental Physiology · doi:10.1113/ep091263 · Cited by 9 · see citing works
“We selected TA muscle for analysis because previous investigations showed that HIIT increases TA muscle growth (Goh et al., 2019; Seldeen et al., 2018) and showed that Klotho affects TA muscle growth following injury or in diseased muscle (Wehling-Henricks et al., 2016; Welc et al., 2020).”
Method
Signs of Alzheimer’s Disease: Tied to Aging
Chen, J., Zhu, Z., & Xu, Y. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26114974 · Cited by 8 · see citing works
“In naturally aging mice, the accumulation of mtDNA mutations in brain tissue is directly associated with reduced complex I/IV activity, which can further disrupt energy metabolism and activate apoptotic pathways [140].”
Endurance exercise preserves physical function in adult and older male C57BL/6 mice: high intensity interval training (HIIT) versus voluntary wheel running (VWR)
Pajski, M. L., Byrd, C., Nandigama, N., Seguin, E., Seguin, A., Fennell, A., & Graber, T. G. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1356954 · Cited by 8 · see citing works
“In work from our lab and others, both VWR and HIIT protocols have demonstrated attenuated frailty and mitigated functional loss in mice (Graber et al., 2015; Gomez-Cabrera et al., 2017; Seldeen et al., 2018; Graber et al., 2019a; Seldeen et al., 2019; Gioscia-Ryan et al., 2021; Bisset et al., 2022).”
BackgroundInfluential
Exercise Partially Rejuvenates Muscle Stem Cells
Larrick, J. W., & Mendelsohn, A. R. (2020) · Rejuvenation Research · doi:10.1089/rej.2020.2359 · Cited by 8 · see citing works
“19,20 Exercise is used as a treatment for frailty in humans with some success, though exercise programs often include a signiﬁcant resistance component as well as aerobic exercise.”
A Narrative Review Evaluating Diet and Exercise as Complementary Medicine for the Management of Alzheimer’s Disease
Szabo‐Reed, A. N., & Key, M. N. (2025) · Nutrients · doi:10.3390/nu17111804 · Cited by 8 · see citing works
The effect of comprehensive assessment and multi-disciplinary management for the geriatric and frail patient
Yao, S., Zheng, P., Ji, L., Ma, Z., Wang, L., Qiao, L., Wan, Y., Sun, N. L., Luo, Y., Yang, J., et al. (2020) · Medicine · doi:10.1097/md.0000000000022873 · Cited by 7 · see citing works
Neuroglobin overexpression in cerebellar neurons of Harlequin mice improves mitochondrial homeostasis and reduces ataxic behavior
Cwerman‐Thibault, H., Malko-Baverel, V., Guilloux, G. L., Ratcliffe, E., Mouri, D., Torres-Cuevas, I., Millán, I., Saubaméa, B., Mignon, V., Boespflug‐Tanguy, O., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.05.030 · Cited by 7 · see citing works
“95 Accelerating rotarod We evaluated motor coordination and balance during 3 consecutive days.”
Preclinical models of frailty: Focus on interventions and their translational impact: A review
Mishra, M., & Howlett, S. E. (2020) · Nutrition and Healthy Aging · doi:10.3233/nha-200103 · Cited by 7 · see citing works
“These studies found that as little as ten minutes of high-intensity interval training three times per week for 8–16 weeks enhanced physical performance and attenuated frailty in ageing male mice [68, 69].”
BackgroundMethod
The impact of a selective androgen receptor modulator (RAD140) on frailty and underlying mechanisms in older male and female C57Bl/6 mice
Heinze-Milne, S., Hodgins, M. L., & Howlett, S. E. (2025) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2025.112054 · Cited by 5 · see citing works
“…SARM treatment would improve grip strength and other measures of functional fitness in aged mice beyond the capabilities of established exercise interventions, such as high-intensity interval training (Seldeen et al., 2018) or voluntary aerobic exercise (Graber et al., 2015), could be fruitful.”
Absence of complement factor H reduces physical performance in C57BL6 mice
Seldeen, K. L., Thiyagarajan, R., Redae, Y. Z., Jacob, A., Troen, B. R., Quigg, R. J., & Alexander, J. J. (2020) · Immunobiology · doi:10.1016/j.imbio.2020.152003 · Cited by 5 · see citing works
Ethical consideration and feasibility demonstration of high-intensity interval training without the use of electrical shocks in mice with and without doxorubicin exposition.
Caru, M., Lalonde, F., Legault, É. P., Curnier, D. Y., St-Pierre, D. H., Comtois, A. S., & Tournoux, F. (2019) · PubMed Central · Cited by 5 · see citing works
Interactive Effects of Enalapril Administration and Novel HIIT Wheel-Bed Training in Aged Rats
Yang, Y., Banerjee, A., Sun, Y., Carter, C. S., & Buford, T. W. (2021) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2021.764686 · Cited by 5 · see citing works
“Recently, animal models of HIIT have been developed, exclusively using mice as a model (15).”
BackgroundMethod
Considerations for Small Animal Physical Rehabilitation
Greising, S. M., Basten, A. M., Schifino, A. G., & Call, J. A. (2022) · Physiology in health and disease · doi:10.1007/978-3-030-95884-8_2 · Cited by 5 · see citing works
Indirect regulation of HIPPO pathway by miRNA mediates high‐intensity intermittent exercise to ameliorate aging skeletal muscle function
Ni, P., Ma, S., Wang, Z., He, J., Zhang, C., Li, B., Yu, X., & Li, F. (2023) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.14338 · Cited by 5 · see citing works
Treadmill training does not enhance skeletal muscle recovery following disuse atrophy in older male mice
Yee, E. M., Hauser, C. T., Petrocelli, J. J., de Hart, N. M. M. P., Ferrara, P. J., Bombyck, P., Fennel, Z. J., van Onselen, L., Mookerjee, S., Funai, K., et al. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1263500 · Cited by 4 · see citing works
“Several studies (Seldeen et al., 2018; Kim et al., 2020) have shown exercise training-mediated increases in grip strength in young adult mice.”
Background
Depending on intensity, exercise improved or worsened pathology in a model of prodromal Parkinson’s disease
Baldauf, L., Feja, M., Stanojlović, M., Strowig, T., Visscher, C., Schaeffer, E., Berg, D., Hankel, J., & Richter, F. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-01200-y · Cited by 3 · see citing works
Acute effects of heat intervention and hybrid exercise on protein synthesis, ribosome biogenesis and autophagy
Normand‐Gravier, T., Solsona, R., Arnould, F., Deriaz, R., Bertrand‐Gaday, C., Borrani, F., Bernardi, H., & Sanchez, A. M. J. (2025) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2025.104169 · Cited by 3 · see citing works
Animal Models of Exercise and Cardiometabolic Disease
Dong, G., RYAN, T. E., & Esser, K. A. (2025) · Circulation Research · doi:10.1161/circresaha.124.325704 · Cited by 4 · see citing works
The Use of Dietary Supplements and Amino Acid Restriction Interventions to Reduce Frailty in Pre-Clinical Models
Bisset, E. S., & Howlett, S. E. (2022) · Nutrients · doi:10.3390/nu14142806 · Cited by 3 · see citing works
Effects of high-intensity interval training on physical and cognitive function in middle-aged male mice
Stephenson, J. C., Tran, T. D., & Graber, T. G. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1589730 · Cited by 2 · see citing works
Ageing muscle across structural and species scales: implications for locomotor performance
Dick, T. J. M., Bird, C., Lindemann, I., Williamson, J. L., & Konno, R. N. (2026) · Journal of Experimental Biology · doi:10.1242/jeb.251614 · Cited by 2 · see citing works
Evaluation of the Effects of 8 Weeks of High-Intensity Interval Training Combined with Niosome-Encapsulated Yerba Mate ( Ilex paraguariensis A. St.-Hil.) Extract on Inflammatory and Oxidative Stress Markers in Rats with Cigarette Smoke–Induced Lung Injury
Pardakhty, S., Pardakhty, A., Jafari, E., Rajizadeh, M. A., & Harijani, S. M. (2026) · Pharmaceutical Sciences · doi:10.34172/ps.026.43114 · Cited by 2 · see citing works
“67,68 In accordance with a recent meta-analysis that emphasized a dose–response relationship between exercise intensity and improvements in pulmonary outcomes, the HIIT protocol applied in the present study was specifically structured to reflect these evidence-based thresholds, particularly within…”
High-intensity interval aerobic and resistance training to counteract low relative lean soft tissue mass in middle age: A randomized controlled trial
Vlietstra, L., Waters, D. L., Jones, L. M., Wilson, L. C., & Meredith-Jones, K. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111991 · Cited by 2 · see citing works
“To date, few studies have investigated the effects of HIIT on sarcopenia (10-13) and the majority of high intensity training protocols conducted in sarcopenic individuals have been with older adults (10, 11) or animal models (12, 13).”
Background
High-Intensity Interval Aerobic Resistance Training to Counteract Low Relative Appendicular Lean Soft Tissue Mass in Middle Age: Study Protocol for a Randomized Controlled Trial
Vlietstra, L., Waters, D. L., Jones, L. M., & Meredith-Jones, K. A. (2020) · JMIR Research Protocols · doi:10.2196/22989 · Cited by 2 · see citing works
“In animal models, HIIT led to a greater muscle mass, larger muscle fiber size, and an increase in mitochondrial biomass in old, sarcopenic, and frail mice compared with nonexercise controls [22].”
Background
A systematic review of exercise protocols applied to athymic mice in tumor-related experiments
Pelosi, A. C., Scariot, P. P. M., Garbuio, A. L. P., Kraemer, M. B., Priolli, D. G., dos Reis, I. G. M., & Messias, L. H. D. (2023) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2023-0027 · Cited by 2 · see citing works
Usability, user experience and acceptance evaluation of CAPACITY: a technological ecosystem for remote follow-up of frailty (Preprint)Preprint
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Background
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“Furthermore, cardiorespiratory ﬁ tness augmentation by exercise-induced cardiac remodeling reduces sarcopenia and prevents neurocognitive deterioration in aging individuals (Chavanelle et al., 2017; Seldeen et al., 2018; Martin-Smith et al., 2020; Tsai et al., 2021).”
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Influential

High intensity interval training improves physical performance in aged female mice: A comparison of mouse frailty assessment tools
Seldeen, K. L., Redae, Y. Z., Thiyagarajan, R., Berman, R. N., Leiker, M. M., & Troen, B. R. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.04.001 · Cited by 32 · see citing works
Data for: High intensity interval training improves physical performance in aged female mice: a comparison of mouse frailty assessment tools
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Endurance exercise preserves physical function in adult and older male C57BL/6 mice: high intensity interval training (HIIT) versus voluntary wheel running (VWR)
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Short Session High Intensity Interval Training and Treadmill Assessment in Aged Mice
Seldeen, K. L., Redae, Y. Z., Thiyagarajan, R., Berman, R. N., Leiker, M. M., & Troen, B. R. (2019) · Journal of Visualized Experiments · doi:10.3791/59138-v · Cited by 4 · see citing works
High-intensity interval training in aged female mice preserves physical, cognitive, and cardiovascular function
Theobald, D., Williamson, P., Johnston, A., Tripp, L., Olabiyi, A. A., Silvers, X., Dickerson, A., Tran, T. D., Brás, L. E. D. C., Sriramula, S., et al. (2026) · GeroScience · doi:10.1007/s11357-026-02489-0

Authors: Seldeen, K. L., Lasky, G., Leiker, M. M., Pang, M., Personius, K. E., & Troen, B. R.
Affiliations: VA Western New York Healthcare System (US)
University at Buffalo, State University of New York (US)
Corresponding author: Troen, Bruce Robert
ORCID: Seldeen, Kenneth Ladd
Personius, Kirkwood Ely
Troen, Bruce Robert
Venue: The Journals of Gerontology Series A
Publisher: Oxford University Press (OUP)
Published: 2017-06-17
Volume: 73
Issue: 4
Pages: 429-437
ISSN: 1079-5006 (ISSN-L)
1758-535X
DOI: 10.1093/gerona/glx120
OpenAlex: W2626525317
Cited by: 104
References: 60
Citations by year: 2026: 8 · 2025: 14 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 14 · 2020: 16 · 2019: 13 · 2018: 6 · 2017: 1
FWCI: 5.98
Type: journal article
Language: en
Open access: closed
Locations: The Journals of Gerontology Series A (publishedVersion, public-domain)
PubMed (publishedVersion)
Funders: Rehabilitation Research and Development (RX001066)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords: high-intensity interval training, frailty, sarcopenia, aging, physical performance, grip strength, treadmill endurance, walking speed, muscle fiber size, muscle mass, exercise intervention, aged mice
MeSH terms: High-Intensity Interval Training, Frailty, Physical Functional Performance, Animals, Body Composition, Exercise Test, Male, Mice, Inbred C57BL, Mitochondria, Muscle, Random Allocation, Absorptiometry, Photon, Muscle, Skeletal, Mice

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High Intensity Interval Training Improves Physical Performance and Frailty in Aged Mice

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