Effects of aging and gender on muscle mass and regulation of Akt-mTOR-p70s6k related signaling in the F344BN rat model

Paturi, Satyanarayana; Gutta, Anil K.; Katta, Anjaiah; Kakarla, Sunil K.; Arvapalli, Ravi Kumar; Gadde, Murali K.; Nalabotu, Siva K.; Rice, Kevin M.; Wu, Mingquan; Blough, Eric R.

doi:10.1016/j.mad.2010.01.008

Cited by 44 publications

(40 citation statements)

References 48 publications

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“…A similar hyper-activation of signaling downstream of mTORC1 has been shown in sarcopenic muscles of aged male Sprague Dawley rats (Kimball et al 2004;Ibebunjo et al 2013), female and male F344BN rats (Paturi et al 2010) and male C57BL/6J x DBA/2J mice (Sandri et al 2013).…”

Section: Discussionsupporting

confidence: 69%

High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state

White

McMahon

et al. 2016

The International Journal of Biochemistry & Cell Biology

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Section: Discussionsupporting

confidence: 69%

High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state

White

McMahon

et al. 2016

The International Journal of Biochemistry & Cell Biology

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“…1). Similarly, the EDL muscle-to-body weight ratio was 24 % (0.39 ± 0.03 g) and 28 % (0.37±0.02 g) lower in the 26-and 30-month-old animals (0.51±0.02 g; (P<0.05)), respectively [3]. Compared to 6-month-old animals, EDL muscle fiber cross-sectional area was 8 and 22 % lower in the 26-and 30-month animals (P <0.05) (Fig.…”

Section: Resultsmentioning

confidence: 78%

“…We utilized the F344BN aging rat which appears to model the age-related atrophy observed in humans [2] and exhibits a decreased incidence of age-related lesions compared to seen in other strains [1]. Previous reports in humans and rats have suggested that the degree and rate of muscle atrophy may differ between muscle type and sex [3,5,6]. Other data has demonstrated that the degree of muscle atrophy continues to increase with age in the male F344BN rat [2,18,19].…”

Section: Discussionmentioning

confidence: 99%

“…The animals and tissues used in this study have been previously examined [3]. Fully mature adult (6 months; n=4), post-menopausal aged (26 months; n= 4), and very aged (30 months; n=4) female F344BN rats were obtained from the National Institute of Aging (Bethesda, MD).…”

Section: Animalsmentioning

confidence: 99%

“…Animal survivability curves developed by the National Institutes on Aging based on large, long-term studies examining Fischer 344/NNiaHSD× Brown Norway/BiNia (F344BN) mortality rates indicate that 6-, 26-, and 30-month-old female rats roughly correspond to the third, seventh, and eighth decade of life in humans [1][2][3]. This latter time point is considered significant by the World Health Organization as it has defined this age group as Belderly^ [4].…”

Section: Introductionmentioning

confidence: 99%

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Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

Rice

Manne

Gadde

et al. 2015

AGE

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Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fastand slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD×Brown Norway/BiNia (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.

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Akt/protein kinase B in skeletal muscle physiology and pathology

Falasca

Blough

2010

Journal Cellular Physiology

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The Akt/protein kinase B is critical regulator of cellular homeostasis with diminished Akt activity being associated with dysregulation of cellular metabolism and cell death while Akt over-activation has been linked to inappropriate cell growth and proliferation. Although the regulation of Akt function has been well characterized in vitro, much less is known regarding the function of Akt in vivo. Here we examine how skeletal muscle Akt expression and enzymatic activity are controlled, the role of Akt in the regulation of skeletal muscle contraction, stress response glucose utilization, and protein metabolism, and the potential participation of this important molecule in skeletal muscle atrophy, aging, and cancer.

show abstract

Effects of aging and gender on muscle mass and regulation of Akt-mTOR-p70s6k related signaling in the F344BN rat model

Cited by 44 publications

References 48 publications

High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state

High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state

Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

Akt/protein kinase B in skeletal muscle physiology and pathology

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