Muscle strength and size are associated with motor unit connectivity in aged mice

Santos

J cachexia sarcopenia muscle

et al. 2020

238

191

Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. Cancer cachexia has long been recognized as a direct cause of complications in cancer patients, reducing quality of life and worsening disease outcomes. Some related conditions, like sarcopenia (age‐related muscle wasting), anorexia (appetite loss) and asthenia (reduced muscular strength and fatigue), share some key features with cancer cachexia, such as weakness and systemic inflammation. Understanding the interplay and the differences between these conditions is critical to advance basic and translational research in this field, improving the accuracy of diagnosis and contributing to finally achieve effective therapies for affected patients.

“…Additionally, a loss of motoneurons, neuromuscular remodelling, denervation and fibre‐type switch may also contribute to reduced numbers of muscle fibres and the overall muscle mass …”

Section: Sarcopeniamentioning

confidence: 99%

Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia

Santos

J cachexia sarcopenia muscle

et al. 2020

238

191

“…While protein homeostasis within the skeletal muscle largely affects its structure and function, further studies should also investigate how changes in protein homeostasis in skeletal muscle might affect the communication between the muscular and nervous systems,, i.e., the neuromuscular junction. Loss of innervation of the skeletal muscle is also a phenotype of ageing and previous studies have shown that the loss of neuronal connection with the muscle, by experimental model of denervation, is associated with impaired motor function and muscle strength . Denervation‐evoked impairment of muscle function will result in further muscle disuse, which may exacerbate muscle atrophy with age .…”

Section: Discussionmentioning

confidence: 99%

Sarcopenia: Tilting the Balance of Protein Homeostasis

2019

Sarcopenia, defined as age‐associated decline of muscle mass and function, is a risk factor for mortality and disability, and comorbid with several chronic diseases such as type II diabetes and cardiovascular diseases. Clinical trials showed that nutritional supplements had positive effects on muscle mass, but not on muscle function and strength, demonstrating our limited understanding of the molecular events involved in the ageing muscle. Protein homeostasis, the equilibrium between protein synthesis and degradation, is proposed as the major mechanism underlying the development of sarcopenia. As the key central regulator of protein homeostasis, the mammalian target of rapamycin (mTOR) is proposed to be essential for muscle hypertrophy. Paradoxically, sustained activation of mTOR complex 1 (mTORC1) is associated with a loss of sensitivity to extracellular signaling in the elderly. It is not understood why sustained mTORC1 activity, which should induce muscle hypertrophy, instead results in muscle atrophy. Here, recent findings on the implications of disrupting protein homeostasis on muscle physiology and sarcopenia development in the context of mTOR/protein kinase B (AKT) signaling are reviewed. Understanding the role of these molecular mechanisms during the ageing process will contribute towards the development of targeted therapies that will improve protein metabolism and reduce sarcopenia.

“…Furthermore, 10-15 month-old mice can be considered as middle-aged, during which time senescence processes and reproductive decline begin to occur [23,24]. With aging, gains in body mass [25][26][27][28] and decreases in locomotor activity are frequently observed [25,[27][28][29][30][31] but see [32].…”

Section: Introductionmentioning

confidence: 99%

Distinct physical condition and social behavior phenotypes of CD157 and CD38 knockout mice during aging

Gerasimenko

Lopatina²,

Shabalova

et al. 2020

Preprint

The ability of CD38 and CD157 to consume nicotinamide adenine dinucleotide (NAD) has received much attention because aging-induced elevation of CD38 expression plays a role in the senescence-related decline in NAD levels. Therefore, it is of interest to examine and compare the effects of age-associated changes on the general health and brain function impairment of Cd157 and Cd38 knockout (CD157 KO and CD38 KO) mice. Body weight and behaviors were measured in 8-week-old (young adult) or 12-month-old (middle-aged) male mice of both KO strains. The locomotor activity, anxiety-like behavior, and social behavior of mice were measured in open field, and three-chamber tests. Middle-aged CD157 KO male mice gained more body weight than young adult mice, while little or no body weight gain was observed in middle-aged CD38 KO mice. Middle-aged CD157 KO mice displayed increased anxiety-like behavior and decreased sociability and interaction compared with young adult KO mice. Middle-aged CD38 KO mice showed less anxiety and hyperactivity than CD157 KO mice, similar to young adult CD38 KO mice. The results reveal marked age-dependent changes in male CD157 KO mice but not in male CD38 KO mice. We discuss the distinct differences in aging effects from the perspective of inhibition of NAD metabolism in CD157 and CD38 KO mice, which may contribute to differential behavioral changes during aging.