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High Intensity Interval Training Improves Physical Performance and Frailty in Aged Mice
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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“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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InfluentialMarcos-Pardo, P. J., González-Gálvez, N., López-Vivancos, A., Espeso-García, A., Martínez-Aranda, L. M., Gea-García, G. M., Orquín-Castrillón, F. J., Carbonell‐Baeza, A., Jiménez‐García, J. D., Velázquez‐Díaz, D., et al. (2020) · Nutrients · doi:10.3390/nu13010008 · Cited by 71
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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 73
Animal Models of Exercise From Rodents to Pythons
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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 52
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“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).”
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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
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“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 39
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“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).”
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
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“and muscle mass in frail aged mice.(73,74) Some studies showed that elder people received HIIT protocol were observed to”
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Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice
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“, 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).”
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“HIIT also enhances locomotor performance in aged mice, which includes muscle mass and strength, grip strength, and mitochondrial biomass (195).”
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“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).”
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Klotho regulates the myogenic response of muscle to mechanical loading and exercise
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“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).”
MethodSigns of Alzheimer’s Disease: Tied to Aging
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“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).”
BackgroundInfluentialExercise Partially Rejuvenates Muscle Stem Cells
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“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.”
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Preclinical models of frailty: Focus on interventions and their translational impact: A review
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“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].”
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“…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
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“Recently, animal models of HIIT have been developed, exclusively using mice as a model (15).”
BackgroundMethodConsiderations 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
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
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
“Several studies (Seldeen et al., 2018; Kim et al., 2020) have shown exercise training-mediated increases in grip strength in young adult mice.”
BackgroundBaldauf, 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
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 4
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
Bisset, E. S., & Howlett, S. E. (2022) · Nutrients · doi:10.3390/nu14142806 · Cited by 5
Stephenson, J. C., Tran, T. D., & Graber, T. G. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1589730 · Cited by 3
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
Pardakhty, S., Pardakhty, A., Jafari, E., Rajizadeh, M. A., & Harijani, S. M. (2026) · Pharmaceutical Sciences · doi:10.34172/ps.026.43114 · Cited by 2
“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…”
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 4
“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).”
BackgroundVlietstra, L., Waters, D. L., Jones, L. M., & Meredith-Jones, K. A. (2020) · JMIR Research Protocols · doi:10.2196/22989 · Cited by 2
“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].”
BackgroundA 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
Pérez‐Rodríguez, R., Villalba‐Mora, E., Valdés-Aragonés, M., Moral, C., Romero, M. M., Abizanda, P., & Rodríguez‐Mañas, L. (2021) · doi:10.2196/preprints.29835 · Cited by 2
Seldeen, K., Wang, N., Muthaiah, R., Treanor, O. P., Davis, A. L., Chaves, L., Thiyagarajan, R., Marzullo, B. J., Yergeau, D., & Troen, B. (2025) · Nutrients · doi:10.3390/nu17233733 · Cited by 1
“HIIE can also yield benefits with less time, as our research group previously reported that a regimen of short-session HIIE (~10 min) increased functional capacity and reduced frailty in both male and female aged mice [18–20].”
Baati, N., Mougenot, N., Lemaître, M., Kirsch, M., Agbulut, O., Ferry, A., & Vitiello, D. (2021) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2021.01097 · Cited by 1
“This training induced an increase in muscle mass, an enlargement of fibers and an improvement of grip strength in trained mice compared to a sedentary group (24,25).”
BackgroundPan, Y., & Ma, L. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823761-8.00004-5 · Cited by 1
Leslie, E., Bosc, L. V. G., Specht, J. W., McKenna, Z. J., Gridley, R., Luna, V., Jones, D. T., Lantz, B. J., Moriwaki, M., Hsiao, Y., et al. (2024) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003479 · Cited by 1
“Trials would otherwise be stopped if mice remained on the Rotarod for 360 s, where trial time would be recorded as 360 s, or if mice remained on the rod through grip strength alone rather than climbing for two complete revolutions within a 10-s period (49).”
Mishra, M., & Howlett, S. E. (2024) · Springer eBooks · doi:10.1007/978-3-031-57361-3_12 · Cited by 2
Fischer, M., Simahendra, A., Straub, T., Brunner, S., Ferraro, B., & Weckbach, L. T. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1682751 · Cited by 1
“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).”
Therapeutic Exercise in Sarcopenia
Senda, M., Hamada, M., Katayama, Y., Ise, M., Hongo, M., & Hamasaki, H. (2021) · リハビリテーション医学 : 日本リハビリテーション医学会誌 · doi:10.2490/jjrmc.58.605
Yao, S., Zheng, P., Ji, L., Ma, Z., Wang, L., Qiao, L., Wan, Y., Sun, N. L., Luo, Y., Yang, J., et al. (2020) · doi:10.21203/rs.3.rs-31960/v1
Mobile Health Technologies for Ambient Assisted Living and Healthcare
Pires, I. M. (2023) · MDPI eBooks · doi:10.3390/books978-3-0365-7027-3
He, J., Ni, P., Rong, X., Yu, Z., Li, B., Zhang, C., Zhang, Z., Wan, Q., Zhong, W., & Li, F. (2025) · Food Science and Human Wellness · doi:10.26599/fshw.2025.9250546
“1A, where mice were reared aging modeling until 19 months of age, and then acclimatized to a running table (Fidi Biologicals, FD000043) training for 1 week, and maximal aerobic running speed (Vpeak) was tested in aged mice[22].”
Xiao, Y., Yang, L., Feng, Y., Guo, M., Zhang, X., Zhao, J., & Chen, W. (2026) · Food Bioscience · doi:10.1016/j.fbio.2026.108772
Normand‐Gravier, T., Solsona, R., Bertrand‐Gaday, C., Issertine, M., Sabatier, F., Arnould, F., Racinais, S., Borrani, F., Bernardi, H., & Sanchez, A. M. J. (2026) · Experimental Physiology · doi:10.1113/ep093111
“Treadmill inclination was 25 ◦ for both SMS and EX sessions to promote gains in muscle hypertrophy, as previously described (Goh et al., 2019; Seldeen et al., 2018).”
InfluentialModeling Sarcopenia: Molecular Mechanisms and Experimental Approaches
Vlasova, Y. A., Sorokina, M. Y., Kostareva, A. A., & Galagudza, М. М. (2026) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093026030026
“There are natural aging mouse models of other ages, e.g., 27 months [6], 22 months [7, 8], and 24 months [9].”
Metadata
- 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
- 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
- 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 (medical) › Nutrition and Health in Aging
- Health Sciences › Medicine › Physiology (medical) › 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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