Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer’s Disease
Open accessAbstract
Increasing evidence indicates that physical activity and exercise training may delay or prevent the onset of Alzheimer’s disease (AD). However, systemic biomarkers that can measure exercise effects on brain function and that link to relevant metabolic responses are lacking. To begin to address this issue, we utilized blood samples of 23 asymptomatic late middle-aged adults, with familial and genetic risk for AD (mean age 65 years old, 50% female) who underwent 26 weeks of supervised treadmill training. Systemic biomarkers implicated in learning and memory, including the myokine Cathepsin B (CTSB), brain-derived neurotrophic factor (BDNF), and klotho, as well as metabolomics were evaluated. Here we show that aerobic exercise training increases plasma CTSB and that changes in CTSB, but not BDNF or klotho, correlate with cognitive performance. BDNF levels decreased with exercise training. Klotho levels were unchanged by training, but closely associated with change in VO 2 peak. Metabolomic analysis revealed increased levels of polyunsaturated free fatty acids (PUFAs), reductions in ceramides, sphingo- and phospholipids, as well as changes in gut microbiome metabolites and redox homeostasis, with exercise. Multiple metabolites (~30%) correlated with changes in BDNF, but not CSTB or klotho. The positive association between CTSB and cognition, and the modulation of lipid metabolites implicated in dementia, support the beneficial effects of exercise training on brain function. Overall, our analyses indicate metabolic regulation of exercise-induced plasma BDNF changes and provide evidence that CTSB is a marker of cognitive changes in late middle-aged adults at risk for dementia.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In humans, chronic exercise increases plasma cathepsin B.
“although chronic exercise does increase plasma levels of cathepsin B145,157.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [145]
In animal models and humans, plasma cathepsin B is positively associated with hippocampus-dependent memory.
“In both animal models and humans, plasma levels of cathepsin B, a lysosomal thiol proteinase produced by muscle, is positively associated with hippocampus-dependent memory145,157.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [145]
In humans, chronic exercise training does not consistently increase plasma BDNF; studies report no change, an increase, or a decrease.
“whereas chronic exercise training has been shown to not alter140, increase or even decrease plasma levels of BDNF140,145.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [145]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · see citing works
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,803 · see citing works
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,003 · see citing works
Exercise training increases size of hippocampus and improves memory
Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., Kim, J. S., Heo, S., Alves, H., White, S. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015950108 · Cited by 4,855 · see citing works
Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015) · Cell · doi:10.1016/j.cell.2015.02.047 · Cited by 3,614 · see citing works
A Neurotrophic Model for Stress-Related Mood Disorders
Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375 · see citing works
Delis-Kaplan Executive Function System
Delis, D. C., Kaplan, E., & Kramer, J. H. (2012) · PsycTESTS Dataset · doi:10.1037/t15082-000 · Cited by 2,683 · see citing works
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388 · see citing works
Exercise builds brain health: key roles of growth factor cascades and inflammation
Cotman, C. W., Berchtold, N. C., & Christie, L.-A. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.06.011 · Cited by 2,268 · see citing works
Gut microbiome alterations in Alzheimer’s disease
Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-13601-y · Cited by 2,137 · see citing works
Sphingolipids and their metabolism in physiology and disease
Hannun, Y. A., & Obeid, L. M. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.107 · Cited by 2,066 · see citing works
Thompson, P. D., Arena, R. A., Riebe, D. A., & Pescatello, L. S. (2013) · Current Sports Medicine Reports · doi:10.1249/jsr.0b013e31829a68cf · Cited by 1,825 · see citing works
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease
Pickard, J. M., Zeng, M. Y., Caruso, R., & Núñez, G. (2017) · Immunological Reviews · doi:10.1111/imr.12567 · Cited by 1,699 · see citing works
Eicosanoid storm in infection and inflammation
Dennis, E. A., & Norris, P. C. (2015) · Nature Reviews Immunology · doi:10.1038/nri3859 · Cited by 1,517 · see citing works
Omega-3 polyunsaturated fatty acids and their health benefits
Shahidi, F., & Ambigaipalan, P. (2018) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-111317-095850 · Cited by 1,390 · see citing works
Transport of brain-derived neurotrophic factor across the blood–brain barrier
Pan, W., Banks, W. A., Fasold, M. B., Bluth, J., & Kastin, A. J. (1998) · Neuropharmacology · doi:10.1016/s0028-3908(98)00141-5 · Cited by 1,354 · see citing works
Physical Activity, Cognition, and Brain Outcomes: A Review of the 2018 Physical Activity Guidelines
ERICKSON, K. I., HILLMAN, C., STILLMAN, C. M., BALLARD, R. M., BLOODGOOD, B., CONROY, D. E., MACKO, R., MARQUEZ, D. X., PETRUZZELLO, S. J., & POWELL, K. E. (2019) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001936 · Cited by 1,214 · see citing works
The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease
Spires-Jones, T. L., & Hyman, B. T. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.004 · Cited by 1,201 · see citing works
Spermidine in health and disease
Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018) · Science · doi:10.1126/science.aan2788 · Cited by 1,154 · see citing works
Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease
Honig, L. S., Vellas, B., Woodward, M., Boada, M., Bullock, R., Borrie, M., Hager, K., Andreasen, N., Scarpini, E., Liu-Seifert, H., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1705971 · Cited by 1,049 · cited 1× · see citing works
“To date there are no effective treatment options for AD patients, and recent pharmacological trials have resulted in failure (3).”
BackgroundBridging animal and human models of exercise-induced brain plasticity
Voss, M. W., Vivar, C., Kramer, A. F., & van Praag, H. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.08.001 · Cited by 1,030 · see citing works
California verbal learning test-second edition
Delis, D. C. (2000) · Medical Entomology and Zoology · Cited by 729 · see citing works
Blood BDNF Concentrations Reflect Brain-Tissue BDNF Levels across Species
Klein, A. B., Williamson, R., Santini, M. A., Clemmensen, C., Ettrup, A., Rios, M., Knudsen, G. M., & Aznar, S. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710000738 · Cited by 726 · see citing works
Exercise-induced oxidative stress: Friend or foe?
Powers, S. K., Deminice, R., Ozdemir, M., Yoshihara, T., Bomkamp, M. P., & Hyatt, H. (2020) · Journal of Sport and Health Science · doi:10.1016/j.jshs.2020.04.001 · Cited by 655 · see citing works
Exercise Modifies the Gut Microbiota with Positive Health Effects
Monda, V., Villano, I., Messina, A., Valenzano, A., Esposito, T., Moscatelli, F., Viggiano, A., Cibelli, G., Chieffi, S., Monda, M., et al. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/3831972 · Cited by 654 · see citing works
Running-induced systemic cathepsin B secretion is associated with memory function
Moon, H. Y., Becke, A., Berron, D., Becker, B., Sah, N., Benoni, G., Janke, E., Lubejko, S. T., Greig, N. H., Mattison, J. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.025 · Cited by 628 · see citing works
Self-citationSphingosine 1-phosphate: Lipid signaling in pathology and therapy
Cartier, A., & Hla, T. (2019) · Science · doi:10.1126/science.aar5551 · Cited by 625 · see citing works
Exercise, brain, and cognition across the life span.
Voss, M. W., Nagamatsu, L. S., Liu-Ambrose, T., & Kramer, A. F. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00210.2011 · Cited by 601 · see citing works
Activation of the Sphingomyelin Cycle Through the Low-Affinity Neurotrophin Receptor
Dobrowsky, R. T., Werner, M. H., Castellino, A. M., Chao, M. V., & Hannun, Y. A. (1994) · Science · doi:10.1126/science.8079174 · Cited by 584 · see citing works
Molecular Choreography of Acute Exercise
Contrepois, K., Wu, S., Moneghetti, K. J., Hornburg, D., Ahadi, S., Tsai, M.-S., Metwally, A. A., Wei, E., Lee-McMullen, B., Quijada, J. V., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.043 · Cited by 502 · see citing works
Yamazaki, Y., Imura, A., Urakawa, I., Shimada, T., Murakami, J., Aono, Y., Hasegawa, H., Yamashita, T., Nakatani, K., Saito, Y., et al. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.06.110 · Cited by 492 · see citing works
Huang, T., Larsen, K. T., Ried‐Larsen, M., Møller, N. C., & Andersen, L. B. (2014) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12069 · Cited by 485 · see citing works
Varma, V. R., Oommen, A. M., Varma, S., Casanova, R., An, Y., Andrews, R. M., O’Brien, R., Pletniková, O., Troncoso, J. C., Toledo, J. B., et al. (2018) · PLoS Medicine · doi:10.1371/journal.pmed.1002482 · Cited by 478 · see citing works
Wu, G. (2020) · Amino Acids · doi:10.1007/s00726-020-02823-6 · Cited by 478 · see citing works
Mueller-Steiner, S., Zhou, Y.-G., Arai, H., Roberson, E., Sun, B.-G., Chen, J., Wang, X., Yu, G.-Q., Esposito, L., Mucke, L., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.027 · Cited by 466 · see citing works
Han, X., Rozen, S., Boyle, S. H., Hellegers, C., Cheng, H., Burke, J. R., Welsh-Bohmer, K. A., Doraiswamy, P. M., & Kaddurah-Daouk, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021643 · Cited by 429 · see citing works
Neurobiological markers of exercise-related brain plasticity in older adults
Voss, M. W., Erickson, K. I., Prakash, R. S., Chaddock, L., Kim, J. S., Alves, H., Szabo, A., Phillips, S. M., Wójcicki, T. R., Mailey, E. L., et al. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.10.021 · Cited by 418 · see citing works
Vascular hippocampal plasticity after aerobic exercise in older adults.
Maass, A., Düzel, S., Goerke, M., Becke, A., Sobieray, U., Neumann, K., Lövden, M., Lindenberger, U., Bäckman, L., Braun-Dullaeus, R., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.114 · Cited by 382 · see citing works
All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis
Vivar, C., Potter, M. C., & van Praag, H. (2012) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2012_220 · Cited by 370 · see citing works
The Role of Exercise in Management of Mental Health Disorders: An Integrative Review
Smith, P. J., & Merwin, R. M. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-060619-022943 · Cited by 360 · see citing works
An update on sphingosine-1-phosphate and other sphingolipid mediators
Fyrst, H., & Saba, J. D. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.392 · Cited by 344 · see citing works
Can physical exercise in old age improve memory and hippocampal function?
Duzel, E., van Praag, H., & Sendtner, M. (2016) · Brain · doi:10.1093/brain/awv407 · Cited by 329 · see citing works
Life Extension Factor Klotho Enhances Cognition
Dubal, D. B., Yokoyama, J. S., Zhu, L., Broestl, L., Worden, K., Wang, D., Sturm, V. E., Kim, D., Klein, E., Yu, G.-Q., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.076 · Cited by 322 · see citing works
Self-citationJakaria, M., Azam, S., Haque, M. E., Jo, S.-H., Uddin, M. S., Kim, I., & Choi, D. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101223 · Cited by 319 · see citing works
Sphingolipids: membrane microdomains in brain development, function and neurological diseases
Olsen, A. S. B., & Færgeman, N. J. (2017) · Open Biology · doi:10.1098/rsob.170069 · Cited by 312 · see citing works
Depression—an underrecognized target for prevention of dementia in Alzheimer’s disease
Dafsari, F. S., & Jessen, F. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0839-1 · Cited by 312 · see citing works
Docosahexaenoic acid (DHA): An essential nutrient and a nutraceutical for brain health and diseases
Sun, G. Y., Simonyi, Á., Fritsche, K. L., Chuang, D. Y., Hannink, M., Gu, Z., Greenlief, C. M., Yao, J. K., Lee, J. C., & Beversdorf, D. Q. (2017) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2017.03.006 · Cited by 311 · see citing works
BDNF mediates improvements in executive function following a 1-year exercise intervention.
Leckie, R. L., Oberlin, L. E., Voss, M. W., Prakash, R. S., Szabo-Reed, A., Chaddock-Heyman, L., Phillips, S. M., Gothe, N. P., Mailey, E., Vieira-Potter, V. J., et al. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00985 · Cited by 307 · see citing works
Berry polyphenols metabolism and impact on human gut microbiota and health
Lavefve, L., Howard, L. R., & Carbonero, F. G. (2019) · Food & Function · doi:10.1039/c9fo01634a · Cited by 269 · see citing works
Deogracias, R., Yazdani, M., Dekkers, M. P. J., Guy, J., Ionescu, M. C. S., Vogt, K. E., & Barde, Y. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206093109 · Cited by 255 · see citing works
Schranner, D., Kastenmüller, G., Schönfelder, M., Römisch‐Margl, W., & Wackerhage, H. (2020) · Sports Medicine - Open · doi:10.1186/s40798-020-0238-4 · Cited by 250 · see citing works
Wipfli, B., Landers, D., Nagoshi, C., & Ringenbach, S. (2011) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/j.1600-0838.2009.01049.x · Cited by 242 · see citing works
Exercise and Hippocampal Memory Systems
Voss, M. W., Soto, C., Yoo, S., Sodoma, M., Vivar, C., & van Praag, H. (2019) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2019.01.006 · Cited by 235 · see citing works
HOOK, V. Y. H., Kindy, M. S., & Hook, G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708362200 · Cited by 209 · see citing works
Muscle metabolism and atrophy: let’s talk about sex
Rosa-Caldwell, M. E., & Greene, N. P. (2019) · Biology of Sex Differences · doi:10.1186/s13293-019-0257-3 · Cited by 202 · see citing works
Recent advances in the application of metabolomics to Alzheimer's Disease
Trushina, E. V., & Mielke, M. M. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.06.014 · Cited by 197 · see citing works
Life Extension Factor Klotho Prevents Mortality and Enhances Cognition in hAPP Transgenic Mice
Dubal, D. B., Zhu, L., Sanchez, P. E., Worden, K., Broestl, L., Johnson, E. C. B., Ho, K., Yu, G.-Q., Kim, D., Bétourné, A., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.5791-12.2015 · Cited by 192 · see citing works
Self-citationSerum sphingomyelins and ceramides are early predictors of memory impairment
Mielke, M. M., Bandaru, V. V. R., Haughey, N. J., Rabins, P. V., Lyketsos, C. G., & Carlson, M. C. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.03.011 · Cited by 188 · see citing works
Devassy, J. G., Leng, S., Gabbs, M., Monirujjaman, M., & Aukema, H. M. (2016) · Advances in Nutrition · doi:10.3945/an.116.012187 · Cited by 184 · see citing works
Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve
Radak, Z. O., Ishihara, K., Tékus, É., Varga, C., Pósa, A., Balogh, L., Boldogh, I. R., & Koltai, E. (2017) · Redox Biology · doi:10.1016/j.redox.2017.02.015 · Cited by 171 · see citing works
Roles of myokines in exercise-induced improvement of neuropsychiatric function
Kim, S., Choi, J., Moon, S., Park, D., Kwak, H., & Kang, J. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-019-02253-8 · Cited by 168 · see citing works
Glycerophosphocholine is elevated in cerebrospinal fluid of Alzheimer patients
Walter, A., Korth, U., Hilgert, M., Hartmann, J., Weichel, O., Hilgert, M., Fassbender, K. C., Schmitt, A., & Klein, J. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.016 · Cited by 165 · see citing works
Wirth, M., Benson, G. S., Schwarz, C., Köbe, T., Grittner, U., Schmitz, D., Sigrist, S. J., Bohlken, J., Stekovic, S., Madeo, F., et al. (2018) · Cortex · doi:10.1016/j.cortex.2018.09.014 · Cited by 163 · see citing works
Nascimento, C. M. C., Pereira, J. R., de Andrade, L. P., Garuffi, M., Pérez, C. A., Kerr, D. S., Talib, L. L., Cominetti, M. R., & Stella, F. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140576 · Cited by 161 · see citing works
la Rosa, A. D., Solana, E., Corpas, R., David Bartrés-faz, A., Pallàs, M., Viña, J., Sanfeliu, C., & Gómez‐Cabrera, M. C. (2019) · Scientific Reports · doi:10.1038/s41598-019-40040-8 · Cited by 161 · see citing works
Ceccom, J., Loukh, N., Lauwers‐Cancès, V., Touriol, C., Nicaise, Y., Gentil, C., Uro‐Coste, E., Pitson, S. M., Maurage, C., Duyckaerts, C. J., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-12 · Cited by 136 · see citing works
Currie, J. M. S., Ramsbottom, R., Ludlow, H., Nevill, A. M., & Gilder, M. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.12.043 · Cited by 135 · see citing works
Matsubara, T., Miyaki, A., Akazawa, N., Choi, Y., Ra, S., Tanahashi, K., Kumagai, H., Oikawa, S., & Maeda, S. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00429.2013 · Cited by 135 · see citing works
Zhao, Y., Zeng, C., Li, X., Yang, T., Kuang, X., & Du, J. (2020) · Aging Cell · doi:10.1111/acel.13239 · Cited by 135 · see citing works
LANGE, K. L., BONDI, M. W., SALMON, D. P., GALASKO, D., DELIS, D. C., THOMAS, R. G., & THAL, L. J. (2002) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617702870096 · Cited by 129 · see citing works
Hyun-Chul, C., Kim, J., Kim, S.-Y., Son, Y. H., Lee, N., & Jung, S. H. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.05.025 · Cited by 128 · see citing works
A Phospholipidomic Analysis of All Defined Human Plasma Lipoproteins
Dashty, M., Kulik, W., Hoek, F. J., Veerman, E. C. I., Peppelenbosch, M. P., & Rezaee, F. (2011) · Scientific Reports · doi:10.1038/srep00139 · Cited by 127 · see citing works
Leon, J., Moreno, A. J., Garay, B. I., Chalkley, R. J., Burlingame, A. L., Wang, D., & Dubal, D. B. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.024 · Cited by 123 · see citing works
Self-citationHook, G., HOOK, V. Y. H., & Kindy, M. S. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110101 · Cited by 111 · see citing works
Kasumov, T., Solomon, T. P. J., Hwang, C. E., Huang, H., Haus, J. M., Zhang, R., & Kirwan, J. P. (2015) · Obesity · doi:10.1002/oby.21117 · Cited by 110 · see citing works
Harrington, M. G., Chiang, J., Pogoda, J. M., Gomez, M. E., Thomas, K., Marion, S., Miller, K. J., Siddarth, P., Yi, X., Zhou, F., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079378 · Cited by 107 · see citing works
Elevated Plasma Ceramides in Depression
Gracia‐García, P., Rao, V., Haughey, N. J., Bandaru, V. V. R., Smith, G. S., Rosenberg, P. B., Lobo, A., Lyketsos, C. G., & Mielke, M. M. (2011) · Journal of Neuropsychiatry · doi:10.1176/jnp.23.2.jnp215 · Cited by 96 · see citing works
Liu, L., Zhou, X., Zhang, Y., Liu, Y., Yang, L., Pu, J., Zhu, D., Zhou, C., & Xie, P. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.03.005 · Cited by 96 · see citing works
Zeng, C., Yang, T.-T., Zhou, H., Zhao, Y., Kuang, X., Duan, W., & Du, J. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.003 · Cited by 87 · see citing works
Sato, Y., Nakamura, T., Aoshima, K., & Oda, Y. (2010) · Analytical Chemistry · doi:10.1021/ac102211r · Cited by 86 · see citing works
Bennett, S. A. L., Valenzuela, N., Xu, H., Franko, B., Fai, S., & Figeys, D. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00168 · Cited by 86 · see citing works
Lysophosphatidylinositol Signalling and Metabolic Diseases
Arifin, S. A., & Falasca, M. (2016) · Metabolites · doi:10.3390/metabo6010006 · Cited by 85 · see citing works
Sphingolipids in Alzheimer's disease, how can we target them?
Crivelli, S. M., Giovagnoni, C., Visseren, L., Scheithauer, A.-L., de Wit, N. M., den Hoedt, S., Losen, M. H., Mulder, M. T., Walter, J., de Vries, H. E., et al. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.12.003 · Cited by 85 · see citing works
Plasma Klotho and Cognitive Decline in Older Adults: Findings From the InCHIANTI Study
Shardell, M. D., Semba, R. D., Rosano, C., Kalyani, R. R., Bandinelli, S., Chia, C. W., & Ferrucci, L. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glv140 · Cited by 84 · see citing works
Skeletal muscle as a regulator of the longevity protein, Klotho
Avin, K. G., Coen, P. M., Huang, W., Stolz, D. B., Sowa, G., Dubé, J. J., Goodpaster, B. H., O'Doherty, R. M., & Ambrosio, F. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00189 · Cited by 83 · see citing works
Metabolomics-based screening of salivary biomarkers for early diagnosis of Alzheimer's disease
Liang, Q., Liu, H., Zhang, T., Jiang, Y., Xing, H., & Zhang, A. (2015) · RSC Advances · doi:10.1039/c5ra19094k · Cited by 81 · see citing works
Longevity factor klotho and chronic psychological stress
Prather, A. A., Epel, E. S., Arenander, J., Broestl, L., Garay, B. I., Wang, D., & Dubal, D. B. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.81 · Cited by 80 · see citing works
Self-citationJung, S. H., Kim, J., Davis, J. M., Blair, S. N., & Hyun-Chul, C. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1658-5 · Cited by 79 · see citing works
Cathepsin B Improves ß-Amyloidosis and Learning and Memory in Models of Alzheimer’s Disease
Embury, C. M., Dyavarshetty, B., Lu, Y., Wiederin, J. L., Ciborowski, P. S., Gendelman, H. E., & Kiyota, T. (2016) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-016-9721-6 · Cited by 78 · see citing works
Acute and regular exercise distinctly modulate serum, plasma and skeletal muscle BDNF in the elderly
Máderová, D., Krumpolec, P., Slobodová, L., Schön, M., Tirpáková, V., Kovaničová, Z., Klepochová, R., Vajda, M., Šutovský, S., Cvečka, J., et al. (2019) · Neuropeptides · doi:10.1016/j.npep.2019.101961 · Cited by 76 · see citing works
Sphingolipid Metabolism: A New Therapeutic Opportunity for Brain Degenerative Disorders
Pardo, A. D., & Maglione, V. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00249 · Cited by 73 · see citing works
<i>KLOTHO</i> heterozygosity attenuates <i>APOE4</i> -related amyloid burden in preclinical AD
Erickson, C. M., Schultz, S. A., Oh, J. M., Darst, B. F., Ma, Y., Norton, D., Betthauser, T., Gallagher, C. L., Carlsson, C. M., Bendlin, B. B., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000007323 · Cited by 70 · see citing works
Self-citationNicolini, C., Michalski, B., Toepp, S. L., Turco, C. V., D'Hoine, T., Harasym, D., Gibala, M. J., Fahnestock, M., & Nelson, A. J. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.03.042 · Cited by 69 · see citing works
Plasma metabolomics in early Alzheimer's disease patients diagnosed with amyloid biomarker
Peña‐Bautista, C., Roca, M., Hervás, D., Cuevas, A., López‐Cuevas, R., Vento, M., Baquero, M., García‐Blanco, A., & Cháfer‐Pericás, C. (2019) · Journal of Proteomics · doi:10.1016/j.jprot.2019.04.008 · Cited by 65 · see citing works
Long term habitual exercise is associated with lower resting level of serum BDNF
Babaei, P., Damirchi, A., Mehdipoor, M., & Tehrani, B. S. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.02.011 · Cited by 63 · see citing works
Park, S.-A., Son, S. Y., Lee, A.-Y., Park, H.-G., Lee, W.-L., & Lee, C. H. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17020541 · Cited by 63 · see citing works
Metabolomics and proteomics profiles of some medicinal plants and correlation with BDNF activity
Gönülalan, E. M., Nemutlu, E., Bayazeid, O., Koçak, E., Yalçın, F. N., & Demirezer, L. Ö. (2019) · Phytomedicine · doi:10.1016/j.phymed.2019.152920 · Cited by 62 · see citing works
Docosahexaenoic acid and the brain- what is its role?
Sinclair, A. J. (2019) · PubMed · doi:10.6133/apjcn.201912_28(4).0002 · Cited by 54 · see citing works
Long, Z., Chen, J., Zhao, Y., Zhou, W. H., Yao, Q., Wang, Y., & He, G. (2020) · Aging · doi:10.18632/aging.103305 · Cited by 52 · see citing works
Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults
Okonkwo, O. C., Xu, G., Dowling, N. M., Bendlin, B. B., LaRue, A. A., Hermann, B. P., Koscik, R. L., Jonaitis, E. M., Rowley, H. A., Carlsson, C. M., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182583047 · Cited by 49 · see citing works
Self-citationGaitán, J. M., Boots, E. A., Dougherty, R. J., Oh, J. M., Ma, Y., Edwards, D. F., Christian, B. T., Cook, D. B., & Okonkwo, O. C. (2019) · Brain Plasticity · doi:10.3233/bpl-190093 · Cited by 49 · see citing works
Self-citationDamirchi, A., Tehrani, B. S., Alamdari, K. A., & Babaei, P. (2014) · Clinical Journal of Sport Medicine · doi:10.1097/jsm.0000000000000082 · Cited by 47 · see citing works
Chua, X. Y., Chai, Y. L., Chew, W. S., Chong, J. R., Ang, H. L., Xiang, P., Camara, K., Howell, A. R., Torta, F. T., Wenk, M. R., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00694-3 · Cited by 47 · see citing works
Metabolites Associated With Circulating Interleukin-6 in Older Adults
Lustgarten, M. S., & Fielding, R. A. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw039 · Cited by 44 · see citing works
Amaro‐Gahete, F. J., De‐la‐O, A., Jurado‐Fasoli, L., Espuch-Oliver, A., de Haro, T., Gutiérrez, Á., Ruiz, J. R., & Castillo, M. J. (2019) · Journal of Sports Sciences · doi:10.1080/02640414.2019.1626048 · Cited by 44 · see citing works
Ji, N., Luan, J., Hu, F., Zhao, Y., Lv, B., Wang, W., Xia, M., Zhao, X., & Lao, K. (2018) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2018.6597 · Cited by 43 · see citing works
Pekar, T., Wendzel, A., Flak, W., Kremer, A., Pauschenwein-Frantsich, S., Gschaider, A., Wantke, F., & Jarisch, R. (2019) · Wiener klinische Wochenschrift · doi:10.1007/s00508-019-01588-7 · Cited by 41 · see citing works
Baranowski, M., Błachnio-Zabielska, A. U., Charmas, M., Helge, J. W., Dela, F., Książek, M., Długołęcka, B., Klusiewicz, A., Chabowski, A., & Górski, J. (2014) · European Journal of Applied Physiology · doi:10.1007/s00421-014-3080-x · Cited by 39 · see citing works
Nagata, Y., Hirayama, A., Ikeda, S., Shirahata, A., Shoji, F., Maruyama, M., Kayano, M., Bundo, M., Hattori, K., Yoshida, S., et al. (2018) · Biomarker Research · doi:10.1186/s40364-018-0119-x · Cited by 39 · see citing works
High-intensity physical exercise increases serum α -klotho levels in healthy volunteers
Tan, S., Chu, M. M., Toussaint, N. D., Cai, M. M., Hewitson, T. D., & Holt, S. G. (2018) · Journal of Circulating Biomarkers · doi:10.1177/1849454418794582 · Cited by 35 · see citing works
Vera, D. M., Rosell‐Valle, C., López-Gambero, A. J., Navarro, J. A., Zambrana-Infantes, E. N., Rivera, P., Santín, L. J., Suárez, J., & de Fonseca, F. R. (2020) · Biology · doi:10.3390/biology9110377 · Cited by 35 · see citing works
Hurtado, M. O., Kohler, I., & de Lange, E. C. M. (2018) · Bioanalysis · doi:10.4155/bio-2018-0135 · Cited by 34 · see citing works
Pena, G. S., Paez, H. G., Johnson, T. K., Halle, J. L., Carzoli, J. P., Visavadiya, N. P., Zourdos, M. C., WHITEHURST, M. A., & Khamoui, A. V. (2020) · International Journal of Chronic Diseases · doi:10.1155/2020/5919501 · Cited by 34 · see citing works
Kim, B.-R., & Kang, S. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17228624 · Cited by 34 · see citing works
Serum Klotho Levels in Trained Athletes
Mostafidi, E., Akbar, M., Nasri, H., Hagjo, A. G., & Ardalan, M. (2016) · Nephro-Urology Monthly · doi:10.5812/numonthly.30245 · Cited by 33 · see citing works
Basal myokine levels are associated with quality of life and depressed mood in older adults
Mucher, P., Batmyagmar, D., Perkmann, T., Repl, M., Radakovics, A., Ponocny‐Seliger, E., Lukas, I., Fritzer‐Szekeres, M., Lehrner, J. P., Knogler, T., et al. (2021) · Psychophysiology · doi:10.1111/psyp.13799 · Cited by 32 · see citing works
Plasma Methionine Sulfoxide in Persons with Familial Alzheimer’s Disease Mutations
Ringman, J. M., Fithian, A. T., Gylys, K. H., Cummings, J. L., Coppola, G., Elashoff, D. A., Praticò, D., Moskovitz, J., & Bitan, G. (2012) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000338546 · Cited by 25 · see citing works
Figueiredo, C., Antunes, B. M., Giacon, T. R., Vanderlei, L. C. M., Campos, E. Z., Peres, F. P., Clark, N. W., Panissa, V. L. G., & Lira, F. S. (2019) · PubMed Central · Cited by 25 · see citing works
Serum klotho: a potential predictor of cerebrovascular disease in hemodialysis patients
Wei, H., Li, H., Song, X., Du, X., Cai, Y., Li, C., Dong, L., & Dong, J. (2019) · BMC Nephrology · doi:10.1186/s12882-019-1232-2 · Cited by 22 · see citing works
Grégoire, C., Berryman, N., St-Onge, F., Vu, T. T. M., Bosquet, L., Arbour, N., & Bherer, L. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00410 · Cited by 20 · see citing works
Analytes and Metabolites Associated with Muscle Quality in Young, Healthy Adults
Lustgarten, M. S., Price, L. L., & Fielding, R. A. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000578 · Cited by 19 · see citing works
Luther, J. A., Enes, J., & Birren, S. J. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00076.2011 · Cited by 19 · see citing works
Książek, M., Charmas, M., Klusiewicz, A., Zabielski, P., Długołęcka, B., Chabowski, A., & Baranowski, M. (2017) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.12910 · Cited by 17 · see citing works
Xiong, J., Zhan, J., Luo, T., Chen, H., Wan, Q., Wang, Y., Wei, B., & Yang, Y. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00610 · Cited by 17 · see citing works
Kotlęga, D., Zembroń-Łacny, A., Gołąb-Janowska, M., Nowacki, P., & Szczuko, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155220 · Cited by 16 · see citing works
Ultramarathon Run Markedly Reduces Plasma Sphingosine-1-phosphate Concentration
Baranowski, M., Górski, J., Kłapcińska, B., Waśkiewicz, Z., & Sadowska‐Krępa, E. (2014) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2013-0093 · Cited by 15 · see citing works
Micielska, K., Kortas, J. A., Gmiat, A., Jaworska, J., Flis, M., Łysak, A., Rodziewicz-Flis, E. A., Żychowska, M., & Ziemann, E. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113235 · Cited by 14 · see citing works
Proteomic biomarkers of cognitive impairment in obstructive sleep apnea syndrome
Lal, C., Hardiman, G., Kumbhare, S., & Strange, C. (2018) · Sleep And Breathing · doi:10.1007/s11325-018-1693-8 · Cited by 13 · see citing works
Effect of Aerobic Exercise on Serum Metabolites in Mice with Hepatocellular Carcinoma After Surgery
Zhao, T., Fang, F., Wang, H., Lv, C., Han, M., Zhang, Z., Wang, F., Bai, L., & Ling, C. (2019) · Medical Science Monitor · doi:10.12659/msm.913377 · Cited by 13 · see citing works
Johnson, T. K., Belcher, D. J., Sousa, C. A., Carzoli, J. P., Visavadiya, N. P., Khamoui, A. V., WHITEHURST, M. A., & Zourdos, M. C. (2020) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2019-0854 · Cited by 11 · see citing works
Rezola‐Pardo, C., Hervás, G., Arrieta, H., Diego, A. H.-D., Ruiz‐Litago, F., Gil, S. M., Rodriguez‐Larrad, A., & Irazusta, J. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111024 · Cited by 10 · see citing works
Germanos, S. D. S., Vieira, B., da Silva, I. R. V., da Cunha, J. J., Nique, S., Striebel, V. L. W., Pochmann, D., & Elsner, V. R. (2019) · PubMed · Cited by 9 · see citing works
Protocol of Aerobic Exercise and Cognitive Health (REACH): A Pilot Study
Gaitán, J. M., Boots, E. A., Dougherty, R. J., Ma, Y., Edwards, D. F., Mitchell, C., Christian, B. T., Cook, D. B., & Okonkwo, O. C. (2020) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-200180 · Cited by 9 · see citing works
Self-citationExercise-induced recovery of plasma lipids perturbed by ageing with nanoflow UHPLC-ESI-MS/MS
Kim, K. U., Yoon, K. J., Park, S., Lee, J. C., Moon, H. Y., & Moon, M. H. (2020) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-020-02933-w · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927 · see citing works
Brain-Derived Neurotrophic Factor in Alzheimer’s Disease and Its Pharmaceutical Potential
Gao, L., Zhang, Y., Sterling, K., & Song, W. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00279-0 · Cited by 606 · see citing works
Marzia Perluigi, A., Domenico, F. D., & Butterfield, D. A. (2023) · Physiological Reviews · doi:10.1152/physrev.00030.2022 · Cited by 306 · see citing works
From Synaptic Plasticity to Neurodegeneration: BDNF as a Transformative Target in Medicine
Toader, C., Șerban, M., Munteanu, O., Covache-Busuioc, R.-A., Enyedi, M., Ciurea, A. V., & Tătaru, C. P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094271 · Cited by 152 · see citing works
Choi, J.-W., Jo, S.-W., Kim, D., Paik, I., & Balakrishnan, R. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103101 · Cited by 144 · see citing works
Can exercise training teach us how to treat Alzheimer's disease?
Huuha, A. M., Norevik, C. S., Moreira, J. B. N., Kobro-Flatmoen, A., Scrimgeour, N., Kivipelto, M., Van Praag, H., Ziaei, M., Sando, S. B., Wisløff, U., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101559 · Cited by 79 · see citing works
Yuan, S., Yang, J., Jian, Y., Lei, Y., Yao, S., Hu, Z., Liu, X., Tang, C., & Liu, W. (2022) · Nutrients · doi:10.3390/nu14194134 · Cited by 74 · see citing works
Physical activity and lifestyle modifications in the treatment of neurodegenerative diseases
Santiago, J. A., & Potashkin, J. A. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1185671 · Cited by 70 · see citing works
Festa, F., Medori, S., & Macrì, M. (2023) · Biomedicines · doi:10.3390/biomedicines11061765 · Cited by 74 · see citing works
The Influence of Intestinal Microbiota on BDNF Levels
Molska, M., Mruczyk, K., Cisek-Woźniak, A., Prokopowicz, W., Szydełko, P., Jakuszewska, Z., Marzec, K., & Trocholepsza, M. (2024) · Nutrients · doi:10.3390/nu16172891 · Cited by 64 · see citing works
From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology
Toader, C., Dobrin, N., Brehar, F.-M., Popa, C., Covache-Busuioc, R.-A., Glavan, L.-A., Costin, H. P., Bratu, B.-G., Corlatescu, A.-D., Popa, A. A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216119 · Cited by 61 · see citing works
Muscle–brain crosstalk mediated by exercise-induced myokines - insights from experimental studies
Kostka, M., Morys, J., Małecki, A., & Nowacka-Chmielewska, M. M. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1488375 · Cited by 68 · see citing works
Major Depressive Disorder and Gut Microbiota: Role of Physical Exercise
de Souza, P. B., Borba, L. A., de Jesus, L. C., Valverde, A. P., Gil‐Mohapel, J., & Rodrigues, A. L. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316870 · Cited by 65 · see citing works
Garavito, A. R., Martínez, V. D., Cortés, E. J., Negrete‐Díaz, J. V., & Rodríguez, L. M. M. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2024.1505879 · Cited by 59 · see citing works
Myokine-mediated muscle-organ interactions: Molecular mechanisms and clinical significance
Yi, J., Chen, J., Yao, X., Zhao, Z., Niu, X., Li, X., Sun, J., Ji, Y., Shang, T., Gong, L., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117326 · Cited by 59 · see citing works
Liu, W., Zhang, J., Wang, Y., Li, J., Chang, J., & Jia, Q. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.927128 · Cited by 50 · see citing works
Xue, B., Waseem, S. M. A., Zhu, Z., Alshahrani, M. A., Nazam, N., Anjum, F., Habib, A. H., Rafeeq, M. M., Nazam, F., & Sharma, M. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.925991 · Cited by 49 · see citing works
Azevedo, C. V., Hashiguchi, D., Campos, H. C., Figueiredo, E. V., Otaviano, S. F. S. D., Penitente, A. R., Arida, R. M., & Longo, B. M. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1131214 · Cited by 48 · see citing works
Exercise and exerkines: Mechanisms and roles in anti-aging and disease prevention
Lu, X., Chen, Y., Shi, Y., Shi, Y., Su, X., Chen, P., Wu, D., & Shi, H. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112685 · Cited by 48 · see citing works
Reparaz-Escudero, I., Izquierdo, M., Bischoff-Ferrari, H. A., Martínez-Lage, P., & Sáez de Asteasu, M. L. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102463 · Cited by 45 · see citing works
Gao, X., Chen, Y., & Cheng, P. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1338875 · Cited by 41 · see citing works
Wang, M., Xie, K., Zhao, S., Jia, N., Zong, Y., Gu, W., & Cai, Y. (2023) · Molecular Medicine · doi:10.1186/s10020-023-00727-1 · Cited by 40 · see citing works
Aerobic exercise, an effective prevention and treatment for mild cognitive impairment
Huang, B., Chen, K., & Li, Y. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1194559 · Cited by 44 · see citing works
Mazo, C. E., Miranda, E. R., Shadiow, J., Vesia, M., & Haus, J. M. (2022) · Brain Plasticity · doi:10.3233/bpl-220137 · Cited by 29 · see citing works
Zeng, Y., Wang, J., Cai, X., Zhang, X., Zhang, J., Peng, M., Xiao, D., Ouyang, H., & Yan, F. (2023) · Geriatric Nursing · doi:10.1016/j.gerinurse.2023.04.012 · Cited by 30 · see citing works
Gulej, R., Patai, R., Ungvari, A., Kállai, A., Tarantini, S., Yabluchanskiy, A., Huffman, D. M., Conboy, M. J., Conboy, I. M., Mika Kivimaki, B., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01657-y · Cited by 29 · see citing works
Campos, H. C., Ribeiro, D. E., Hashiguchi, D., Glaser, T., Milanis, M. D. S., Gimenes, C., Suchecki, D., Arida, R. M., Ulrich, H., & Longo, B. M. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1132825 · Cited by 28 · see citing works
Soldan, A., Alfini, A. J., Pettigrew, C. A., Faria, A. V., Hou, X., Lim, C., Lu, H., Spira, A. P., Zipunnikov, V., & Albert, M. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.04.006 · Cited by 28 · see citing works
Bacanoiu, M. V., Dănoiu, M., Rusu, L., & Marin, M. I. (2023) · Antioxidants · doi:10.3390/antiox12051008 · Cited by 27 · see citing works
Current Perspectives: Obesity and Neurodegeneration - Links and Risks
Kueck, P. J., Morris, J. K., & Stanford, J. A. (2024) · Degenerative Neurological and Neuromuscular Disease · doi:10.2147/dnnd.s388579 · Cited by 29 · see citing works
Caruso, M. G., Nicolas, S., Lucassen, P. J., Mul, J. D., O’Leary, O. F., & Nolan, Y. M. (2024) · Brain Plasticity · doi:10.3233/bpl-230157 · Cited by 25 · see citing works
Exercise and the organ-brain axis: Regulation of neurological disorders by emerging exerkines
Dai, Y., Dou, X., Nie, B., Sun, Y., Chen, P., Fu, C., Zhang, X., Chu, Y., Gao, Q., Ge, Y., et al. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107913 · Cited by 25 · see citing works
Bangen, K. J., Calcetas, A. T., Thomas, K. R., Wierenga, C. E., Smith, C. N., Bordyug, M., Brenner, E. K., Wing, D., Chen, C., Liu, T. T., et al. (2023) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617723000140 · Cited by 23 · see citing works
Vints, W. A. J., Gökçe, E., Langeard, A., Павлова, Ю., Çevik, Ö. S., Ziaaldini, M. M., Todri, J., Lena, O., Sakkas, G. K., Jak, S., et al. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1213057 · Cited by 26 · see citing works
Martín-Vírgala, J., Martín-Carro, B., Fernández-Villabrille, S., Ruiz-Torres, M., Gómez‐Alonso, C., Rodríguez-García, M., Martín, J. L. F., Alonso‐Montes, C., Panizo, S., Cannata-Andía, J. B., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031843 · Cited by 23 · see citing works
Klotho: An Emerging Factor With Ergogenic Potential
Arroyo, E., Troutman, A. D., Moorthi, R. N., Avin, K. G., Coggan, A. R., & Lim, K. J. (2022) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2021.807123 · Cited by 22 · see citing works
Muscle fiber type-dependence effect of exercise on genomic networks in aged mice models
Lee, S. M., Lee, M. C., Bae, W. R., Yoon, K. J., & Moon, H. Y. (2022) · Aging · doi:10.18632/aging.204024 · Cited by 22 · see citing works
Self-citationMulti-omics studies reveal ameliorating effects of physical exercise on neurodegenerative diseases
Guo, Y., Wang, S., Chao, X., Li, D., Wang, Y., Guo, Q., & Chen, T. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1026688 · Cited by 21 · see citing works
Wei, C., Wu, X., Li, C., Zhang, Y., Yuan, Q., & Huang, R. (2025) · The FASEB Journal · doi:10.1096/fj.202402572r · Cited by 19 · see citing works
Increasing the health span: unique role for exercise
Gaesser, G. A., Hall, S. E., Angadi, S. S., Poole, D. C., & Racette, S. B. (2025) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00049.2025 · Cited by 19 · see citing works
The Relationship Between Exercise, Cathepsin B, and Cognitive Functions: Systematic Review
Gökçe, E., & Gün, N. (2023) · Perceptual and Motor Skills · doi:10.1177/00315125231176980 · Cited by 18 · see citing works
Physical activity, cathepsin B, and cognitive health
Yu, Q., Zhang, Z., Herold, F., Ludyga, S., Kuang, J., Chen, Y., Liu, Z., Erickson, K. I., Goodpaster, B. H., Cheval, B., et al. (2025) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.12.010 · Cited by 17 · see citing works
Self-citationExercise Delays Brain Ageing Through Muscle‐Brain Crosstalk
Pourteymour, S., Majhi, R. K., Norheim, F., & Drevon, C. A. (2025) · Cell Proliferation · doi:10.1111/cpr.70026 · Cited by 19 · see citing works
de Almeida, M. F., Farizatto, K. L. G., Almeida, R. S., & Bahr, B. A. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102162 · Cited by 17 · see citing works
Li, J., Liu, T., Xian, M., Zhou, K., & Wei, J. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.03.001 · Cited by 17 · see citing works
Recent evidence and progress for developing precision nursing in symptomatology: A scoping review
Liu, Q., Wang, F., Wang, G., Liu, L., & Hu, X. (2023) · International Nursing Review · doi:10.1111/inr.12816 · Cited by 16 · see citing works
Lisi, V., Senesi, G., & Balbi, C. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.09.021 · Cited by 16 · see citing works
Lim, G., Lee, H., & Lim, Y. (2022) · Biomedicines · doi:10.3390/biomedicines10102529 · Cited by 15 · see citing works
Moghadasi, M., Akbari, F., & Najafi, P. (2024) · Molecular Biology Reports · doi:10.1007/s11033-023-09197-4 · Cited by 13 · see citing works
Wang, N., Zhu, S., Chen, S., Zou, J., Zeng, P., & Tan, S. (2025) · Reviews in the Neurosciences · doi:10.1515/revneuro-2024-0147 · Cited by 12 · see citing works
Liquid biopsy in neurodegenerative disease: A minimally invasive approach for early diagnosis
Udayakumar, S., Girigoswami, A., & Girigoswami, K. (2025) · Clinica Chimica Acta · doi:10.1016/j.cca.2025.120517 · Cited by 12 · see citing works
Peripheral immune and metabolic regulation of Aβ and Tau by exercise in Alzheimer’s disease
Yu, Y., & Chen, K. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1678526 · Cited by 12 · see citing works
Fasting, a Potential Intervention in Alzheimer's Disease
Zeng, Z., Zhang, H., Wang, X., Shen, J., & Chen, D. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2303050 · Cited by 12 · see citing works
Synbiotics in Alzheimer’s disease: mechanisms, clinical evidence, and therapeutic prospects
Lin, Y., Weng, R., Pan, H., Hou, Y., Sun, Y., & Wen, J. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07064-3 · Cited by 12 · see citing works
Running throughout Middle-Age Keeps Old Adult-Born Neurons Wired
Vivar, C., Peterson, B., Pinto, A., Janke, E., & van Praag, H. (2023) · eNeuro · doi:10.1523/eneuro.0084-23.2023 · Cited by 12 · see citing works
Metabolomic and proteomic applications to exercise biomedicine
Wilkinson, D. J., Crossland, H., & Atherton, P. J. (2024) · Translational Exercise Biomedicine · doi:10.1515/teb-2024-2006 · Cited by 13 · see citing works
Xie, G., Xu, Z., Li, F., Kong, M., Wang, P., & Shao, Y. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04164-2 · Cited by 12 · see citing works
Cathepsin B and Muscular Strength are Independently Associated with Cognitive Control
Kim, J., McKenna, C. F., Salvador, A. F., Scaroni, S. E., Askow, A. T., Cerna, J., Cannavale, C. N., Paluska, S. A., Lisio, M. D., Petruzzello, S. J., et al. (2022) · Brain Plasticity · doi:10.3233/bpl-210136 · Cited by 11 · see citing works
Chang, Y., Erickson, K. I., Aghjayan, S. L., Chen, F., Li, R., Shih, J.-R., Chang, S.-H., Huang, C., & Chu, C. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.929789 · Cited by 10 · see citing works
Jin-li, H., Yang, W., Zhang, Q., Feng, H., Wang, X., Li, H., Zhou, S., & Xiao, S. (2023) · Nutrients · doi:10.3390/nu15071694 · Cited by 11 · see citing works
Hao, Z., Liu, K., Zhou, L., & Chen, P. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1193031 · Cited by 10 · see citing works
Grzelak, N., Kaczmarek, D., & Mrówczyński, W. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1268648 · Cited by 10 · see citing works
Guo, Y., Huang, L., Kuang, J., Sun, T., Zhang, X., Tian, H., Xie, F., Chen, T., & Guo, Q. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14921 · Cited by 10 · see citing works
Exercise-mediated circulating metabolites for brain health
Wang, M., Nasb, M., Wu, T., Jia, M., & So, K. (2024) · Advanced Exercise and Health Science · doi:10.1016/j.aehs.2024.11.001 · Cited by 11 · see citing works
Ding, L., Lou, L., Zhang, M., & Zhang, X. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2024.112652 · Cited by 11 · see citing works
The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases
López-Valdés, H. E., Hernández-Lucas, M., Rodríguez-Fabián, G. D. J., Esteban-Román, N. F., Gutiérrez-Juárez, R., Arrieta‐Cruz, I., & Martínez‐Coria, H. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178551 · Cited by 10 · see citing works
Exercise attenuates the hallmarks of aging: Novel perspectives
Qiu, Y., Fernández‐Garcia, B., Lehmann, H. I., Li, G., Kroemer, G., López-Otı́n, C., & Xiao, J. (2025) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2025.101108 · Cited by 15 · see citing works
Zhang, Y., Wei, R., Zhang, M., Zhang, K.-X., Zhang, J.-Y., Fang, S., Ge, Y., Kong, X.-Y., Chen, G.-H., & Li, X. (2023) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2023.1271653 · Cited by 9 · see citing works
Pinto, A., Haytural, H., Loss, C. M., Álvarez, C., Ertas, A., Curtis, O., Williams, A. R., Murphy, G., Salleng, K. J., Gografe, S., et al. (2025) · Aging Cell · doi:10.1111/acel.70242 · Cited by 8 · see citing works
Muscle-brain crosstalk as a driver of brain health in aging
McNeish, B. L., Miljkovic, I., Liu-Ambrose, T. Y. L., Ambrosio, F., Esser, K. A., Fahnestock, M. L., & Rosano, C. (2025) · GeroScience · doi:10.1007/s11357-025-01833-0 · Cited by 10 · see citing works
Kim, Y., Jamrasi, P., Li, X., Ahn, S., Sung, Y., Ahn, S., Kang, Y., & Song, W. J. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-230946 · Cited by 7 · see citing works
Téglás, T., & Radak, Z. O. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1572687 · Cited by 10 · see citing works
Lipoproteins and metabolites in diagnosing and predicting Alzheimer’s disease using machine learning
Wang, F., Wang, A., Huang, Y., Gao, W., Xu, Y., Zhang, W., Guo, G., Song, W., Kong, Y., Wang, Q., et al. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02141-w · Cited by 7 · see citing works
Potential Role of Extracellular Vesicles in Mediating Effects of Exercise on Brain Function
Moon, H. Y., & van Praag, H. (2025) · Advances in neurobiology · doi:10.1007/978-981-95-0066-6_8 · Cited by 7 · see citing works
Self-citationWang, Y., Sun, X., He, B., Yu, S., & Yu, Y. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70620 · Cited by 6 · see citing works
Effects of Exercise-Induced Changes in Myokine Expression on the Tumor Microenvironment
Gunasekara, N., Clauss, D., & Bloch, W. (2024) · Sports Medicine International Open · doi:10.1055/a-2283-1663 · Cited by 6 · see citing works
Effects of moderate intensity exercise on liver metabolism in mice based on multi-omics analysis
Wang, F., Wu, W., He, X.-J., Qian, P., Chang, J.-H., Lu, Z.-X., Guo, J., Bao, Y., Guan, H., & Zhang, T. (2024) · Scientific Reports · doi:10.1038/s41598-024-82150-y · Cited by 8 · see citing works
Li, J., Zhang, F., Zhao, L., & Dong, C. (2023) · Reviews in the Neurosciences · doi:10.1515/revneuro-2023-0006 · Cited by 6 · see citing works
Zhou, J., Zhang, X., Yin, S., Xue, S., He, Q., Chen, S., & Xue, X. (2026) · Translational Neurodegeneration · doi:10.1186/s40035-026-00537-5 · Cited by 5 · see citing works
Mruczyk, K., Molska, M., Wójciak, R. W., Śliwicka, E., & Cisek-Woźniak, A. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112449 · Cited by 5 · see citing works
Yang, L., Li, P., Huang, X., Wang, C., Zeng, Y., Wang, J., Yao, X., & Meng, J. (2025) · Genes · doi:10.3390/genes16020197 · Cited by 5 · see citing works
An exercise infusion benefits brain function
Pinto, A., & van Praag, H. (2022) · Cell Research · doi:10.1038/s41422-022-00621-1 · Cited by 5 · see citing works
Exercise-induced Brain-derived neurotrophic factor regulation in the brain dysfunctions
Rezaee, Z., Marandi, S. M., Alaei, H., & Esfarjani, F. (2023) · Science & Sports · doi:10.1016/j.scispo.2022.08.003 · Cited by 5 · see citing works
Logue, E. M., Hilsabeck, R. C., & Melamed, E. (2024) · The Clinical Neuropsychologist · doi:10.1080/13854046.2024.2335115 · Cited by 5 · see citing works
Ayed, I. B., Ammar, A., Aouichaoui, C., Naija, S., Amor, S. B., Glenn, J. M., Chtourou, H., Jahrami, H., Trabelsi, K., Trabelsi, Y., et al. (2024) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-249003 · Cited by 5 · see citing works
Niu, J., Li, Y., Zhou, Q., Liu, X., Yu, P., Gao, F., Gao, X., & Wang, Q. (2024) · Aging Clinical and Experimental Research · doi:10.1007/s40520-024-02846-z · Cited by 5 · see citing works
Lingling, S., Chen, H., Li, X., Jichen, C., Li, C., & Chuhuai, W. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1581481 · Cited by 4 · see citing works
Ramoneda, M., Medina-Casanovas, J., Aquino, M. B. N., & Guerra-Balic, M. (2024) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2024.06.004 · Cited by 4 · see citing works
He, Y., Liu, B., Yang, F., Yang, Q., Xu, B., Liu, L., & Chen, Y. (2024) · Aging Cell · doi:10.1111/acel.14244 · Cited by 4 · see citing works
Relationship of Klotho with cognition and dementia: A systematic review and meta-analysis
Liu, Y., Huang, J., & Xu, B. (2025) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2025.104417 · Cited by 3 · see citing works
Break free from cognitive impairment: The magic of exercise-induced molecules
Liu, W., Zhang, H., Zeng, Q., Cai, W., Rui, Y., & Sun, J. (2025) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2025.101117 · Cited by 3 · see citing works
Yuan, S., Lin, L., Liu, J., Lin, Q., Wang, S., Wu, J., Xu, D., Liu, Y., Lee, J. Y., & Qiu, L. (2026) · Life Sciences · doi:10.1016/j.lfs.2026.124500 · Cited by 3 · see citing works
Phan, J. M.-P., Yi, J., Foote, J. H. A., Ayabe, A. R. K., Guan, K., Garland, T., & Parfitt, K. D. (2024) · Restorative Neurology and Neuroscience · doi:10.1177/09226028241290400 · Cited by 3 · see citing works
Grabowska, K., Grabowski, M., Morys, J., Olakowska, E., Małecki, A., Barski, J. J., & Nowacka-Chmielewska, M. M. (2025) · Scientific Reports · doi:10.1038/s41598-025-10014-0 · Cited by 3 · see citing works
Barnes, J. N., Burns, J. M., Bamman, M. M., Billinger, S. A., Bodine, S. C., Booth, F. W., Brassard, P., Clemons, T. A., Fadel, P. J., Geiger, P. C., et al. (2022) · Brain Plasticity · doi:10.3233/bpl-220146 · Cited by 3 · see citing works
Combined Exercise and Vitamin D on Brain-Derived Neurotrophic Factor
Hoseini, R., Hoseini, Z., & Bahmani, E. (2023) · Biochemistry · doi:10.5772/intechopen.112021 · Cited by 3 · see citing works
Special Issue: Peripheral Factors and Neural Plasticity
van Praag, H., & Wrann, C. D. (2022) · Brain Plasticity · doi:10.3233/bpl-229001 · Cited by 3 · see citing works
(2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01126-x · Cited by 3 · see citing works
Global multi-omics analysis of exerkines in progressive treadmill-exercised rodentsPreprint
Taha, H. B. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.08.627439 · Cited by 3 · see citing works
Zhou, Z., Yu, X., Tian, E., Guo, Z., Chen, J., Guo, J., Shi, S., Xu, W., Zhai, N., Qiao, C., et al. (2026) · CNS Neuroscience & Therapeutics · doi:10.1002/cns.70773 · Cited by 2 · see citing works
- Authors
- Gaitán, J. M., Moon, H. Y., Stremlau, M., Dubal, D. B., Cook, D. B., Okonkwo, O. C., & van Praag, H.
- Affiliations
- University of Wisconsin–Madison (US)
- Seoul National University (KR)
- National Institute on Aging (US)
- University of California, San Francisco (US)
- Corresponding author
- Okonkwo, Ozioma C.
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2021-05-20
- Volume
- 12
- Pages
- 660181-660181
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC8173166
- OpenAlex
- W3161410779
- Cited by
- 160
- References
- 136
- Citations by year
- 2026: 39 · 2025: 33 · 2024: 32 · 2023: 34 · 2022: 20 · 2021: 2
- FWCI
- 15.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Alzheimer's Association
- Extendicare Foundation
- National Institutes of Health
- Florida Department of Health
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- aerobic exercise training, Alzheimer's disease risk, systemic biomarkers, cathepsin B, brain-derived neurotrophic factor, Klotho, cognitive performance, metabolomics, lipid metabolism, polyunsaturated fatty acids, ceramide, gut microbiota metabolites, redox homeostasis, peak oxygen uptake, treadmill training, middle-aged adults, dementia prevention
- MeSH terms
- Gastrointestinal Microbiome, Klotho Proteins, Aged, Aged, 80 and over, Alzheimer Disease, Cathepsin B, Cognition, Female, Humans, Hydroxyproline, Male, Middle Aged, Proline, Risk Factors, Biomarkers, Exercise, Fatty Acids, Omega-3, Brain-Derived Neurotrophic Factor, Lipid Metabolism, Metabolomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
