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Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

Published version
Peer-reviewed

Type

Article

Change log

Authors

Tarry-Adkins, Jane L 
Fernandez-Twinn, Denise S 
Chen, Jian Hua 
Hargreaves, Iain P 
Neergheen, Viruna 

Abstract

'Developmental programming', which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed 'recuperated') in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phoxand nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by increased tumor necrosis factor-α (TNFα) and interleukin-1β (IL1β) protein levels. Taken together, we demonstrate, for the first time to our knowledge, an accelerated aging phenotype in skeletal muscle in the context of developmental programming. These findings may pave the way for suitable interventions in at-risk populations.

Description

Keywords

Developmental programming, Mitochondria, Oxidative stress, Skeletal muscle, Aging, Animals, Antioxidants, Biomarkers, DNA Damage, Diet, Female, Growth and Development, Inflammation, Male, Maternal Nutritional Physiological Phenomena, Muscle, Skeletal, NF-kappa B, Oxidants, Oxidative Stress, Phenotype, Rats, Wistar, Telomere Shortening

Journal Title

Disease Models & Mechanisms

Conference Name

Journal ISSN

1754-8403
1754-8411

Volume Title

9

Publisher

Company of Biologists
Sponsorship
Medical Research Council (MC_UU_12012/4)
British Heart Foundation (None)
British Heart Foundation (None)
Diabetes UK (None)
Medical Research Council (MC_PC_12012)
This work was supported by The British Heart Foundation [PG/09/037/27387, FS/09/029/27902]; Medical Research Council [MC_UU_12012/4] and Diabetes UK [12/0004508].