Improved health by combining dietary restriction and promoting muscle growth in DNA repair‐deficient progeroid mice

Autor: Wilbert P. Vermeij, Khalid Alyodawi, Ivar vanGalen, Jennie L. von derHeide, María B. Birkisdóttir, Lisanne J. van'tSant, Rutger A. Ozinga, Daphne S.J. Komninos, Kimberly Smit, Yvonne M.A. Rijksen, Renata M.C. Brandt, Sander Barnhoorn, Dick Jaarsma, Sathivel Vaiyapuri, Olli Ritvos, Tobias B. Huber, Oliver Kretz, Ketan Patel
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 15, Iss 6, Pp 2361-2374 (2024)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13570
Popis: Abstract Background Ageing is a complex multifactorial process, impacting all organs and tissues, with DNA damage accumulation serving as a common underlying cause. To decelerate ageing, various strategies have been applied to model organisms and evaluated for health and lifespan benefits. Dietary restriction (DR, also known as caloric restriction) is a well‐established long‐term intervention recognized for its universal anti‐ageing effects. DR temporarily suppresses growth, and when applied to progeroid DNA repair‐deficient mice doubles lifespan with systemic health benefits. Counterintuitively, attenuation of myostatin/activin signalling by soluble activin receptor (sActRIIB), boosts the growth of muscle and, in these animals, prevents muscle wasting, improves kidney functioning, and compresses morbidity. Methods Here, we investigated a combined approach, applying an anabolic regime (sActRIIB) at the same time as DR to Ercc1Δ/− progeroid mice. Following both single treatments and combined, we monitored global effects on body weight, lifespan and behaviour, and local effects on muscle and tissue weight, muscle morphology and function, and ultrastructural and transcriptomic changes in muscle and kidney. Results Lifespan was mostly influenced by DR (extended from approximately 20 to 40 weeks; P
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