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      Muscle and Bone Health in Postmenopausal Women: Role of Protein and Vitamin D Supplementation Combined with Exercise Training

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          Abstract

          Menopause is an age-dependent physiological condition associated with a natural decline in oestrogen levels, which causes a progressive decrease of muscle mass and strength and bone density. Sarcopenia and osteoporosis often coexist in elderly people, with a prevalence of the latter in elderly women. The profound interaction between muscle and bone induces a negative resonance between the two tissues affected by these disorders worsening the quality of life in the postmenopausal period. It has been estimated that at least 1 in 3 women over age 50 will experience osteoporotic fractures, often requiring hospitalisation and long-term care, causing a large financial burden to health insurance systems. Hormonal replacement therapy is effective in osteoporosis prevention, but concerns have been raised with regard to its safety. On the whole, the increase in life expectancy for postmenopausal women along with the need to improve their quality of life makes it necessary to develop specific and safe therapeutic strategies, alternative to hormonal replacement therapy, targeting both sarcopenia and osteoporosis progression. This review will examine the rationale and the effects of dietary protein, vitamin D and calcium supplementation combined with a specifically-designed exercise training prescription as a strategy to counteract these postmenopausal-associated disorders.

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          Differential regulation of mTORC1 by leucine and glutamine

          The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates environmental and intracellular signals to regulate cell growth. Amino acids stimulate mTORC1 activation at the lysosome in a manner thought to be dependent on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and the vacuolar H+-adenosine triphosphatase (v-ATPase). We report that leucine and glutamine stimulate mTORC1 by Rag GTPase-dependent and -independent mechanisms, respectively. Glutamine promoted mTORC1 translocation to the lysosome in RagA and RagB knockout cells and required the v-ATPase but not the Ragulator. Furthermore, we identified the adenosine diphosphate ribosylation factor-1 GTPase to be required for mTORC1 activation and lysosomal localization by glutamine. Our results uncover a signaling cascade to mTORC1 activation independent of the Rag GTPases and suggest that mTORC1 is differentially regulated by specific amino acids.
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            Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group.

            J Kanis (1994)
            The criteria required for an effective screening strategy for osteoporosis are largely met in Caucasian women. The disease is common and readily diagnosed by the measurement of bone mineral with single- or dual-energy absorptiometry. Such measurements have high specificity but lower sensitivity, so that the value of the technique is greater for those identified as being at higher risk. Against this background there is little evidence that osteoporosis can usefully be tackled by a public health policy to influence risk factors such as smoking, exercise and nutrition. This suggests that it is appropriate to consider targetting of treatment with agents affecting bone metabolism to susceptible individuals. Since the main benefits of the use of hormone replacement therapy (HRT) are probably on cardiovascular morbidity, the major role for selective screening is to direct non-HRT interventions. An appropriate time to consider screening and intervention is at the menopause, but screening at later ages is also worthy of consideration. Since the cost of screening is low and that of bone-active drugs is high, the selective use of screening techniques will improve the cost-benefit ratio of intervention.
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              Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle.

              Aging skeletal muscles suffer a steady decline in mass and functional performance, and compromised muscle integrity as fibrotic invasions replace contractile tissue, accompanied by a characteristic loss in the fastest, most powerful muscle fibers. The same programmed deficits in muscle structure and function are found in numerous neurodegenerative syndromes and disease-related cachexia. We have generated a model of persistent, functional myocyte hypertrophy using a tissue-restricted transgene encoding a locally acting isoform of insulin-like growth factor-1 that is expressed in skeletal muscle (mIgf-1). Transgenic embryos developed normally, and postnatal increases in muscle mass and strength were not accompanied by the additional pathological changes seen in other Igf-1 transgenic models. Expression of GATA-2, a transcription factor normally undetected in skeletal muscle, marked hypertrophic myocytes that escaped age-related muscle atrophy and retained the proliferative response to muscle injury characteristic of younger animals. The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                16 August 2018
                August 2018
                : 10
                : 8
                : 1103
                Affiliations
                [1 ]Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 (PU) Urbino, Italy; deborah.agostini@ 123456uniurb.it (D.A.); sabrina.zeppa@ 123456uniurb.it (S.D.Z.); francesco.lucertini@ 123456uniurb.it (F.L.); giosue.annibalini@ 123456uniurb.it (G.A.); marco.gervasi@ 123456uniurb.it (M.G.); carlo.ferrimarini@ 123456uniurb.it (C.F.M.); giovanni.piccoli@ 123456uniurb.it (G.P.); vilberto.stocchi@ 123456uniurb.it (V.S.); piero.sestili@ 123456uniurb.it (P.S.)
                [2 ]Interuniversity Institute of Myology (IIM), University of Urbino Carlo Bo, 61029 (PU) Urbino, Italy
                Author notes
                [* ]Correspondence: elena.barbieri@ 123456uniurb.it ; Tel.: +39-0722-303-417; Fax: +39-0722-303-401
                [†]

                These Authors contributed equally to this review.

                Author information
                https://orcid.org/0000-0003-0225-666X
                https://orcid.org/0000-0001-5879-0752
                https://orcid.org/0000-0003-3134-4511
                https://orcid.org/0000-0002-6914-4905
                https://orcid.org/0000-0001-7112-1780
                https://orcid.org/0000-0002-6866-997X
                https://orcid.org/0000-0001-5879-0752
                https://orcid.org/0000-0002-3480-7983
                https://orcid.org/0000-0001-9412-1660
                Article
                nutrients-10-01103
                10.3390/nu10081103
                6116194
                30115856
                9f2cd77c-8945-4073-ade6-69bc4e5e334c
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 July 2018
                : 13 August 2018
                Categories
                Review

                Nutrition & Dietetics
                postmenopausal women,sarcopenia,osteoporosis,exercise,dietary protein,vitamin d
                Nutrition & Dietetics
                postmenopausal women, sarcopenia, osteoporosis, exercise, dietary protein, vitamin d

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