TY - JOUR
T1 - Improved health by combining dietary restriction and promoting muscle growth in DNA repair-deficient progeroid mice
AU - Vermeij, Wilbert P.
AU - Alyodawi, Khalid
AU - van Galen, Ivar
AU - von der Heide, Jennie L.
AU - Birkisdóttir, María B.
AU - van't Sant, Lisanne J.
AU - Ozinga, Rutger A.
AU - Komninos, Daphne S.J.
AU - Smit, Kimberly
AU - Rijksen, Yvonne M.A.
AU - Brandt, Renata M.C.
AU - Barnhoorn, Sander
AU - Jaarsma, Dick
AU - Vaiyapuri, Sathivel
AU - Ritvos, Olli
AU - Huber, Tobias B.
AU - Kretz, Oliver
AU - Patel, Ketan
PY - 2024
Y1 - 2024
N2 - 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 Ercc1?/? 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
AB - 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 Ercc1?/? 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
KW - Ageing
KW - Dietary restriction
KW - Kidney
KW - Muscle
KW - Myostatin
KW - Progeria
U2 - 10.1002/jcsm.13570
DO - 10.1002/jcsm.13570
M3 - Article
SN - 2190-5991
VL - 15
SP - 2361
EP - 2374
JO - Journal of cachexia, sarcopenia and muscle
JF - Journal of cachexia, sarcopenia and muscle
IS - 6
ER -