The prevalence of sarcopenia is increasing and effective interventions are required to prevent or reverse age-related muscle loss. However, it often is challenging, expensive and time-consuming to develop and test the effectiveness of such interventions and translational animal models that are adequately mimicking the underlying physiological pathways are scarce. Strong predictors for the incidence of sarcopenia include a sedentary life-style and malnutrition. TNO has therefore recently developed a new and short (2 weeks) mouse model for muscle atrophy that combines caloric restriction with partial immobilization (of one hindleg). This combination model exhibits loss of muscle mass and function. Transcriptome analysis demonstrated that the underlying pathways of this combination model revealed more similarity with the human underlying pathways than aged mice. In addition to the combination models, we previously demonstrated a beneficial treatment effect in the CR alone model (van den Hoek AM et al., Metabolism 2019).
In addition to the abovementioned models, TNO has several technologies (including AMS; Low dose 14C-alanine incorporation to enable high sensitive detection and tracing of protein turnover in muscle) available for muscle related translational and clinical research. In addition, we perform biomarkers research and can support companies with sensors/eHealth solutions in this therapeutic indication.

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□ TNO's Translational Muscle Pipeline

Recent Publication:
  □   Anabolic effects of salbutamol are lost upon immobilization. J Cachexia Sarcopenia Muscle 2025; 16: e70114. doi.org/10.1002/jcsm.70114. de Jong JCBC, Jameson TSO, Andrews RC, Dunlop MV, Abdelrahman DR, Murton AJ, Caspers MPM, Worms N, van Nieuwkoop A, Keijzer N, Cheng Q, GuigasB, van Duijn E, Vaes WHJ, Nieuwenhuizen AG, Keijer J, Wall BT, Verschuren L, Stephens FB,| van den Hoek AM, Dirks ML.

  □   Blood-based biomarkers for early frailty are sex-specific: validation of a combined in silico prediction and data-driven approach. Geroscience 2025; 47:3741-3758. doi: 10.1007/s11357-024-01449-w. de Jong JCBC, Caspers MPM, Dulos R, Snabel J, van der Hoek MD, van der Leij FR, Kleemann R, Keijer J, Nieuwenhuizen AG, van den Hoek AM, Verschuren L. van de Meene MRC, van den Hoek AM, Hanemaaijer R, Verschuren L, de Jong JCBC. In vitro muscle contraction: A technical review on electrical pulse stimulation in C2C12 cells. Exp Physiol 2025; 1-16. DOI: 10.1113/EP092677.

  □   Translatability of mouse muscle-aging for humans: the role of sex. Geroscience 2024; 46: 3341-3360. doi: 10.1007/s11357-024-01082-7. de Jong JCBC, Caspers MPM, Worms N, Keijzer N, Kleemann R, Menke AL, Nieuwenhuizen AG, Keijer J, Verschuren L, van den Hoek AM.

  □   Caloric restriction combined with immobilization as translational model for sarcopenia expressing key-pathways of human pathology. Aging Dis 2023; 14: 937-957. doi: 10.14336/AD.2022.1201. de Jong JCBC, Caspers MPM, Keijzer N, Worms N, Attema J, de Ruiter C, Lek S, Nieuwenhuizen AG, Keijer J, Menke AL, Kleemann R, Verschuren L, van den Hoek AM.

  □   Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk. Metabolism 2021;124:154873. doi: 10.1016/j.metabol.2021.154873. van den Hoek AM, de Jong JCBC, Worms N, van Nieuwkoop A, Voskuilen M, Menke AL, Lek S, Caspers MPM, Verschuren L, Kleemann R.

  □   Intramuscular short-chain acylcarnitines in elderly people are decreased in (pre-)frail females, but not in males. FASEB J 2020; 34:11658-11671. Doi: 10.1096/fj.202000493R. van der Hoek MD, Nieuwenhuizen AG, Kuda O, Bos P, Paluchova V, Verschuren L, van den Hoek AM, Kleemann R, Veeger NJGM, van der Leij FR, Keijer J.

  □   A novel nutritional supplement prevents muscle loss and accelerates muscle mass recovery in caloric-restricted mice. Metabolism 2019;97:57-67. doi: 10.1016/j.metabol.2019.05.012. van den Hoek AM, Zondag GCM, Verschuren L, de Ruiter C, Attema J, de Wit EC, Schwerk AMK, Guigas B, Lek S, Rietman A, Strijker R, Kleemann R.

Collaboration program
In addition, TNO is leader of a research consortium that focuses on a better understanding of sarcopenia, including the underlying mechanism. An unique human cohort is studied to further validate the translatability of our models and to identify biomarkers. In addition, male/female differences will be studied.

Future directions
 ・We are also investigating Muscle Health in relation to cognition.
 ・Muscle health in relation to menopause.
 ・Muscle Health in relation to the use of GLP-1 analogues (semaglutide/Ozempic).