Secreted Protein Acidic and Rich in Cysteine as an Exercise-Induced Gene: Towards Novel Molecular Therapies for Immobilization-Related Muscle Atrophy in Elderly Patients
Abstract:Long periods of immobilization, among other etiologies, would result is muscle atrophy. Exercise is the best approach to reverse this atrophy. However, the limited or the non-ability to perform the required physical activity for such patients and the limited pharmacological options make developing novel therapeutic approaches a necessity. Within this context, secreted protein acidic and rich in cysteine (SPARC) has been characterized as an exercise-induced gene. Whereas the knock-out of this gene leads to a ph… Show more
“…We also suggested that, considering SPARC mediates exercise-induced benefits [ 49 ], SPARC administration could represent a substitute to exercise [ 50 ]. This is of a specific importance especially for elderly patients who are not able to perform the required physical activity due to diseases, hospitalisation, or physical disabilities [ 51 ]. This would allow them to possibly receive some of the exercise benefits although they are not able to perform exercises.…”
Ageing is defined by the decline in the biological and physiological functions over time, which leads to health problems and increases risks of diseases. The modern societies are characterised by an ageing population, which represents challenges for the healthcare system. Within this context, there is a need to better understand the biological mechanisms beyond ageing in order to optimise geriatric therapies and medical approaches. Herein, we suggest exploring the genetic and epigenetic patterns related to ageing and correlate them with the ageing-related phenotype of the biological entities in order to establish mechanistic links and map the molecular pathways. Such links would have diverse implications in basic research, in clinics, as well as for therapeutic studies.
“…We also suggested that, considering SPARC mediates exercise-induced benefits [ 49 ], SPARC administration could represent a substitute to exercise [ 50 ]. This is of a specific importance especially for elderly patients who are not able to perform the required physical activity due to diseases, hospitalisation, or physical disabilities [ 51 ]. This would allow them to possibly receive some of the exercise benefits although they are not able to perform exercises.…”
Ageing is defined by the decline in the biological and physiological functions over time, which leads to health problems and increases risks of diseases. The modern societies are characterised by an ageing population, which represents challenges for the healthcare system. Within this context, there is a need to better understand the biological mechanisms beyond ageing in order to optimise geriatric therapies and medical approaches. Herein, we suggest exploring the genetic and epigenetic patterns related to ageing and correlate them with the ageing-related phenotype of the biological entities in order to establish mechanistic links and map the molecular pathways. Such links would have diverse implications in basic research, in clinics, as well as for therapeutic studies.
“…Briefly, studies using genetically-modified mice suggested that exercise-induced muscle phenotype changes are SPARC -dependent [ 18 ] and showed that SPARC overexpression mimics exercise effects in mice, whereas Sparc KO leads to an accelerated ageing phenotype which is improved by exercise [ 19 ]. Together, these data suggest that at least a part of the exercise benefits are mediated by SPARC , which would be anti-aging, and with effects against various metabolic disorders and age-related diseases [ 20 , 21 ]. SPARC is expressed in various situations and has even been suggested as a molecular physiological and pathological biomarker [ 22 ] for which its measure could optimize personalized medicine [ 23 ].…”
Section: Secreted Protein Acidic and Rich In Cysteine (
Spa...mentioning
The strong benefits of exercise, in addition to the development of both the therapeutic applications of physical activity and molecular biology tools, means that it has become very important to explore the underlying molecular patterns linking exercise and its induced phenotypic changes. Within this context, secreted protein acidic and rich in cysteine (SPARC) has been characterized as an exercise-induced protein that would mediate and induce some important effects of exercise. Herein, we suggest some underlying pathways to explain such SPARC-induced exercise-like effects. Such mechanistic mapping would not only allow us to understand the molecular processes of exercise and SPARC effects but would also highlight the potential to develop novel molecular therapies. These therapies would be based on mimicking the exercise benefits via either introducing SPARC or pharmacologically targeting the SPARC-related pathways to produce exercise-like effects. This is of a particular importance for those who do not have the ability to perform the required physical activity due to disabilities or diseases. The main objective of this work is to highlight selected potential therapeutic applications deriving from SPARC properties that have been reported in various publications.
“…Functional genomics explorations of obesity and the factors that impact its development (diet, exercise, etc.) [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ] have revealed specific related genes and improved our molecular understanding of obesity development.…”
Section: Modern Health Challenges and Obesitymentioning
Obesity represents a heavy burden for modern healthcare. The main challenge facing obesity research progress is the unknown underlying pathways, which limits our understanding of the pathogenesis and developing therapies. Obesity induces specific biochemical environments that impact the different cells and tissues. In this piece of writing, we suggest mimicking obesity-induced in vivo biochemical environments including pH, lipids, hormones, cytokines, and glucose within an in vitro environment. The concept is to reproduce such biochemical environments and use them to treat the tissue cultures, explant cultures, and cell cultures of different biological organs. This will allow us to clarify how the obesity-induced biochemistry impacts such biological entities. It would also be important to try different environments, in terms of the compositions and concentrations of the constitutive elements, in order to establish links between the effects (impaired regeneration, cellular inflammation, etc.) and the factors constituting the environment (hormones, cytokines, etc.) as well as to reveal dose-dependent effects. We believe that such approaches will allow us to elucidate obesity mechanisms, optimize animal models, and develop therapies as well as novel tissue engineering applications.
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