Potential Satellite Cell-Linked Biomarkers in Aging Skeletal Muscle Tissue: Proteomics and Proteogenomics to Monitor Sarcopenia

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Sarcopenia (Sp) is the loss of skeletal muscle mass associated with aging which causes an involution of muscle function and strength. Satellite cells (Sc) are myogenic stem cells, which are activated by injury or stress, and repair muscle tissue. With advancing age, there is a decrease in the efficiency of the regenerative response of Sc. Diagnosis occurs with the Sp established by direct assessments of muscle. However, the detection of biomarkers in real-time biofluids by liquid biopsy could represent a step-change in the understanding of the molecular biology and heterogeneity of Sp. A total of 13 potential proteogenomic biomarkers of Sp by their physiological and biological interaction with Sc have been previously described in the literature. Increases in the expression of GDF11, PGC-1α, Sirt1, Pax7, Pax3, Myf5, MyoD, CD34, MyoG, and activation of Notch signaling stimulate Sc activity and proliferation, which could modulate and delay Sp progression. On the contrary, intensified expression of GDF8, p16INK4a, Mrf4, and activation of the Wnt pathway would contribute to early Sp development by directly inducing reduced and/or altered Sc function, which would attenuate the restorative capacity of skeletal muscle. Additionally, tissue biopsy remains an important diagnostic tool. Proteomic profiling of aged muscle tissues has shown shifts toward protein isoforms characteristic of a fast-to-slow transition process and an elevated number of oxidized proteins. In addition, a strong association between age and plasma values of growth differentiation factor 15 (GDF-15) has been described and serpin family A member 3 (serpin A3n) was more secreted by atrophied muscle cells. The identification of these new biomarkers holds the potential to change personalized medicine because it could predict in real time the course of Sp by monitoring its evolution and assessing responses to potential therapeutic strategies.

Related collections

Most cited references 85

Record: found
Abstract: found
Article: found

Is Open Access

Sarcopenia: revised European consensus on definition and diagnosis

Alfonso Cruz-Jentoft, Gulistan Bahat, Jürgen Bauer … (2018)

Abstract Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

0 comments Cited 2734 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Sarcopenia

Alfonso Cruz-Jentoft, Avan Sayer (2019)

Sarcopenia is a progressive and generalised skeletal muscle disorder involving the accelerated loss of muscle mass and function that is associated with increased adverse outcomes including falls, functional decline, frailty, and mortality. It occurs commonly as an age-related process in older people, influenced not only by contemporaneous risk factors, but also by genetic and lifestyle factors operating across the life course. It can also occur in mid-life in association with a range of conditions. Sarcopenia has become the focus of intense research aiming to translate current knowledge about its pathophysiology into improved diagnosis and treatment, with particular interest in the development of biomarkers, nutritional interventions, and drugs to augment the beneficial effects of resistance exercise. Designing effective preventive strategies that people can apply during their lifetime is of primary concern. Diagnosis, treatment, and prevention of sarcopenia is likely to become part of routine clinical practice.

0 comments Cited 860 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders.

Darren J. Baker, Tobias Wijshake, Tamar Tchkonia … (2012)

Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells. Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16(Ink4a)-positive senescent cells upon drug treatment. In tissues--such as adipose tissue, skeletal muscle and eye--in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.