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

'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), p67phox and 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.

Tarry-Adkins JL ，Fernandez-Twinn DS ，Chen JH ，Hargreaves IP ，Neergheen V ，Aiken CE ，Ozanne SE ... -  《-》

A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats.

Tarry-Adkins JL ，Aiken CE ，Ashmore TJ ，Fernandez-Twinn DS ，Chen JH ，Ozanne SE ... -  《-》

Poor maternal nutrition followed by accelerated postnatal growth leads to alterations in DNA damage and repair, oxidative and nitrosative stress, and oxidative defense capacity in rat heart.

Tarry-Adkins JL ，Martin-Gronert MS ，Fernandez-Twinn DS ，Hargreaves I ，Alfaradhi MZ ，Land JM ，Aiken CE ，Ozanne SE ... -  《-》

Coenzyme Q10 prevents hepatic fibrosis, inflammation, and oxidative stress in a male rat model of poor maternal nutrition and accelerated postnatal growth.

Tarry-Adkins JL ，Fernandez-Twinn DS ，Hargreaves IP ，Neergheen V ，Aiken CE ，Martin-Gronert MS ，McConnell JM ，Ozanne SE ... -  《-》

Poor maternal nutrition followed by accelerated postnatal growth leads to telomere shortening and increased markers of cell senescence in rat islets.

Tarry-Adkins JL ，Chen JH ，Smith NS ，Jones RH ，Cherif H ，Ozanne SE ... -  《-》