5-HT2C agonism as a neurotherapeutic for sarcopenia: preclinical proof of concept

McGrath R, McGrath BM, Al Snih S, et al. Collective weakness and fluidity in weakness status associated with basic self-care limitations in older Americans. Am J Med Open. 2024;11:100065. https://doi.org/10.1016/j.ajmo.2024.100065.

Article  PubMed  PubMed Central  Google Scholar 

Beaudart C, Rolland Y, Cruz-Jentoft AJ, et al. Assessment of muscle function and physical performance in daily clinical practice: A position paper endorsed by the European society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO). Calcif Tissue Int. 2019;105(1):1–14. https://doi.org/10.1007/s00223-019-00545-w.

Article  CAS  PubMed  Google Scholar 

Duchowny KA, Clarke PJ, Peterson MD. Muscle weakness and physical disability in older Americans: Longitudinal findings from the U.S. health and retirement study. J Nutr Health Aging. 2018;22(4):501–7. https://doi.org/10.1007/s12603-017-0951-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

World Health Organization. Ageing and health. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health. Accessed 29 Aug 2024.

World population projected to reach 9.8 billion in 2050, and 11.2 billion in 2100. United Nations. Accessed 10/1/2024, 2024.

Ethgen O, Beaudart C, Buckinx F, Bruyère O, Reginster JY. The future prevalence of sarcopenia in Europe: A claim for public health action. Calcif Tissue Int. 2017;100(3):229–34. https://doi.org/10.1007/s00223-016-0220-9.

Article  CAS  PubMed  Google Scholar 

Seeman TE, Merkin SS, Crimmins EM, Karlamangla AS. Disability trends among older Americans: National health and nutrition examination surveys, 1988–1994 and 1999–2004. Am J Public Health. 2010;100(1):100–7. https://doi.org/10.2105/ajph.2008.157388.

Article  PubMed  PubMed Central  Google Scholar 

García-Hermoso A, Cavero-Redondo I, Ramírez-Vélez R, et al. Muscular strength as a predictor of all-cause mortality in an apparently healthy population: a systematic review and meta-analysis of data from approximately 2 million men and women. Arch Phys Med Rehabil. 2018;99(10):2100-2113.e5. https://doi.org/10.1016/j.apmr.2018.01.008.

Article  PubMed  Google Scholar 

Garmany A, Yamada S, Terzic A. Longevity leap: mind the healthspan gap. NPJ Regen Med. 2021;6(1):57. https://doi.org/10.1038/s41536-021-00169-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kwak JY, Kwon KS. pharmacological interventions for treatment of sarcopenia: current status of drug development for sarcopenia. Ann Geriatr Med Res. 2019;23(3):98–104. https://doi.org/10.4235/agmr.19.0028.

Article  PubMed  PubMed Central  Google Scholar 

Rolland Y, Dray C, Vellas B, Barreto PS. Current and investigational medications for the treatment of sarcopenia. Metabolism. 2023;149:155597. https://doi.org/10.1016/j.metabol.2023.155597.

Article  CAS  PubMed  Google Scholar 

Tieland M, Trouwborst I, Clark BC. Skeletal muscle performance and ageing. J Cachexia Sarcopenia Muscle. 2018;9(1):3–19. https://doi.org/10.1002/jcsm.12238.

Article  PubMed  Google Scholar 

Clark BC. Neural mechanisms of age-related loss of muscle performance and physical function. J Gerontol A Biol Sci Med Sci. 2023;78(Suppl 1):8–13. https://doi.org/10.1093/gerona/glad029.

Article  PubMed  PubMed Central  Google Scholar 

Ashe J. Force and the motor cortex. Behav Brain Res. 1997;87(2):255–69. https://doi.org/10.1016/s0166-4328(97)00752-3.

Article  CAS  PubMed  Google Scholar 

Heckman CJ, Mottram C, Quinlan K, Theiss R, Schuster J. Motoneuron excitability: the importance of neuromodulatory inputs. Clin Neurophysiol. 2009;120(12):2040–54. https://doi.org/10.1016/j.clinph.2009.08.009.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Enoka RM, Duchateau J. Rate coding and the control of muscle force. Cold Spring Harb Perspect Med. 2017;7(10):a029702. https://doi.org/10.1101/cshperspect.a029702.

Article  PubMed  PubMed Central  Google Scholar 

Wages NP, Mousa MH, Clark LA, et al. Reductions in motor unit firing are associated with clinically meaningful leg extensor weakness in older adults. Calcif Tissue Int. 2023. https://doi.org/10.1007/s00223-023-01123-x.

Article  PubMed  PubMed Central  Google Scholar 

Orssatto LBR, Borg DN, Pendrith L, Blazevich AJ, Shield AJ, Trajano GS. Do motoneuron discharge rates slow with aging? A systematic review and meta-analysis. Mech Ageing Dev. 2022;203:111647. https://doi.org/10.1016/j.mad.2022.111647.

Article  PubMed  Google Scholar 

Clark LA, Manini TM, Wages NP, Simon JE, Russ DW, Clark BC. Reduced neural excitability and activation contribute to clinically meaningful weakness in older adults. J Gerontol A Biol Sci Med Sci. 2021;76(4):692–702. https://doi.org/10.1093/gerona/glaa157.

Article  PubMed  Google Scholar 

Orssatto LBR, Borg DN, Blazevich AJ, Sakugawa RL, Shield AJ, Trajano GS. Intrinsic motoneuron excitability is reduced in soleus and tibialis anterior of older adults. Geroscience. 2021;43(6):2719–35. https://doi.org/10.1007/s11357-021-00478-z.

Article  PubMed  PubMed Central  Google Scholar 

Heckman CJ, Johnson M, Mottram C, Schuster J. Persistent inward currents in spinal motoneurons and their influence on human motoneuron firing patterns. Neuroscientist. 2008;14(3):264–75. https://doi.org/10.1177/1073858408314986.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Heckman CJ. Computer simulations of the effects of different synaptic input systems on the steady-state input-output structure of the motoneuron pool. J Neurophysiol. 1994;71(5):1727–39. https://doi.org/10.1152/jn.1994.71.5.1727.

Article  CAS  PubMed  Google Scholar 

Martino G, Valli G, Sarto F, Franchi MV, Narici MV, Dev G. Neuromodulatory contribution to muscle force production after short-term unloading and active recovery. Med Sci Sports Exerc. 2024;56(9):1830–9. https://doi.org/10.1249/mss.0000000000003473.

Article  PubMed  PubMed Central  Google Scholar 

Orssatto LBR, Rodrigues P, Mackay K, et al. Intrinsic motor neuron excitability is increased after resistance training in older adults. J Neurophysiol. 2023;129(3):635–50. https://doi.org/10.1152/jn.00462.2022.

Article  PubMed  Google Scholar 

Thorstensen JR, Henderson TT, Kavanagh JJ. Serotonergic and noradrenergic contributions to motor cortical and spinal motoneuronal excitability in humans. Neuropharmacology. 2024;242:109761. https://doi.org/10.1016/j.neuropharm.2023.109761.

Article  CAS  PubMed  Google Scholar 

Murray KC, Stephens MJ, Ballou EW, Heckman CJ, Bennett DJ. Motoneuron excitability and muscle spasms are regulated by 5-HT2B and 5-HT2C receptor activity. J Neurophysiol. 2011;105(2):731–48. https://doi.org/10.1152/jn.00774.2010.

Article  PubMed  Google Scholar 

Nardelli P, Powers R, Cope TC, Rich MM. Increasing motor neuron excitability to treat weakness in sepsis. Ann Neurol. 2017;82(6):961–71. https://doi.org/10.1002/ana.25105.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Henderson TT, Taylor JL, Thorstensen JR, Kavanagh JJ. Excitatory drive to spinal motoneurones is necessary for serotonin to modulate motoneurone excitability via 5-HT(2) receptors in humans. Eur J Neurosci. 2024;59(1):17–35. https://doi.org/10.1111/ejn.16190.

Article  CAS  PubMed  Google Scholar 

Goodlich BI, Del Vecchio A, Horan SA, Kavanagh JJ. Blockade of 5-HT(2) receptors suppresses motor unit firing and estimates of persistent inward currents during voluntary muscle contraction in humans. J Physiol. 2023;601(6):1121–38. https://doi.org/10.1113/jp284164.

Article  CAS  PubMed  Google Scholar 

Clar

留言 (0)

沒有登入
gif