Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods

Attaix, Didier; Mosoni, Laurent; Dardevet, Dominique; Combaret, Lydie; Mirand, Philippe Patureau; Grizard, Jean

doi:10.1016/j.biocel.2005.04.009

Cited by 111 publications

(78 citation statements)

References 64 publications

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“…7B). These findings are in accord with a prior finding that glucocorticoids fail to stimulate muscle protein breakdown in aged rats as they do in younger animals (16).…”

Section: The Ubiquitin Ligases Chip E6ap and Murf1 Increase In Mussupporting

confidence: 92%

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Muscle Wasting in Aged, Sarcopenic Rats Is Associated with Enhanced Activity of the Ubiquitin Proteasome Pathway

Altun

Besche

Overkleeft

et al. 2010

Journal of Biological Chemistry

192

155

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Among the hallmarks of aged organisms are an accumulation of misfolded proteins and a reduction in skeletal muscle mass ("sarcopenia"). We have examined the effects of aging and dietary restriction (which retards many age-related changes) on components of the ubiquitin proteasome system (UPS) in muscle. The hindlimb muscles of aged (30 months old) rats showed a marked loss of muscle mass and contained 2-3-fold higher levels of 26S proteasomes than those of adult (4 months old) controls. 26S proteasomes purified from muscles of aged and adult rats showed a similar capacity to degrade peptides, proteins, and an ubiquitylated substrate, but differed in levels of proteasome-associated proteins (e.g. the ubiquitin ligase E6AP and deubiquitylating enzyme USP14). Also, the activities of many other deubiquitylating enzymes were greatly enhanced in the aged muscles. Nevertheless, their content of polyubiquitylated proteins was higher than in adult animals. The aged muscles contained higher levels of the ubiquitin ligase CHIP, involved in eliminating misfolded proteins, and MuRF1, which ubiquitylates myofibrillar proteins. These muscles differed from ones rapidly atrophying due to disease, fasting, or disuse in that Atrogin-1/MAFbx expression was low and not inducible by glucocorticoids. Thus, the muscles of aged rats showed many adaptations indicating enhanced proteolysis by the UPS, which may enhance their capacity to eliminate misfolded proteins and seems to contribute to the sarcopenia. Accordingly, dietary restriction decreased or prevented the aging-associated increases in proteasomes and other UPS components and reduced muscle wasting.

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“…7B). These findings are in accord with a prior finding that glucocorticoids fail to stimulate muscle protein breakdown in aged rats as they do in younger animals (16).…”

Section: The Ubiquitin Ligases Chip E6ap and Murf1 Increase In Mussupporting

confidence: 92%

“…Although DR alters many age-related metabolic changes, its affects on protein turnover have not been previously investigated. A number of studies of aged humans and rodents have shown decreased rates of protein synthesis in muscle, which was associated with insulin resistance (16) (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Muscle Wasting in Aged, Sarcopenic Rats Is Associated with Enhanced Activity of the Ubiquitin Proteasome Pathway

Altun

Besche

Overkleeft

et al. 2010

Journal of Biological Chemistry

192

155

View full text Add to dashboard Cite

show abstract

“…In humans and rodents alike, a number of mechanisms have been suggested to underpin sarcopenia: 1) loss of innervation 2) disuse 3) impaired maintenance and repair including decline in endo-, para-and autocrine signaling (e.g. IGF-1) 4) systemic inflammation 5) imbalance between protein synthesis and degradation and 6) poor nutrition (Adamo and Farrar, 2006;Attaix et al, 2005;Paddon-Jones and Rasmussen, 2009;Roth et al, 2006;Solomon and Bouloux, 2006). However, awaiting more definitive evidence it remains unclear if the mechanism behind loss of muscle mass in elderly is different from that operating in muscle atrophy in young individuals.…”

Section: Regulation Of Muscle Mass and Tentative Mechanisms In Sarcopmentioning

confidence: 99%

“…One of the most characteristic features of the aged is a change in body composition and human cross-sectional and longitudinal studies consistently demonstrate gain in fat mass and decline in lean mass (Attaix et al, 2005). Skeletal muscle mass is gradually reduced through both atrophy and loss of myofibers, and along with this connective tissue and intramyocellular lipids increase ( Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Although sarcopenia is widely recognized it remains poorly understood and has not received appropriate attention until quite recently. Sarcopenia is often assumed to have a multi-factorial background (Adamo and Farrar, 2006;Attaix et al, 2005;Paddon-Jones and Rasmussen, 2009;Roth et al, 2006;Solomon and Bouloux, 2006). A sedentary life-style combined with periods of prolonged bed-rest during illnesses has well-established detrimental effects on muscle mass and function (Janssen et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Cellular Degradation Machineries in Age-Related Loss of Muscle Mass (Sarcopenia)

Altun¹,

Grönholdt‐Klein²,

Wang³

et al. 2012

Senescence

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Reduced cerebellar gray matter is a neural signature of physical frailty

Chen

Chou²,

Liu

et al. 2015

Human Brain Mapping

105

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Physical frailty has been recognized as a clinical syndrome resulting from declines in various physiological systems; however, the role of the central nervous system in the pathophysiology of frailty remains unclear. The I-Lan Longitudinal Aging Study randomly sampled community-dwelling people aged 50 or older for a brain magnetic resonance imaging study. All participants were assessed for frailty status (robust, prefrail, and frail) based on the presence of five frailty components: slow walking speed, muscle weakness, low physical activity, exhaustion and weight loss (Fried criteria). Gray matter volume (GMV) changes associated with frailty status and individual frailty components were examined. Overall, 456 participants (64.0 ± 8.5 years, 47.6% women) were included in this study. The prefrail (n = 178, 39.0%) and frail (n = 19, 4.2%) subjects were grouped for analysis. The prefrail-frail group showed reduced GMV, compared to the robust group (n = 259, 56.8%), in the cerebellum, hippocampi, middle frontal gyri, and several other cerebral regions (corrected P < 0.05). Each frailty component was associated with GMV changes in functionally related brain areas. Hierarchical cluster analysis categorized these components into three subsets. Motor-related components, including weakness, low activity, and slowness, comprised one subset with a common cerebellar involvement. Exhaustion and weight loss were the other two subsets without cerebellar changes. To conclude, physical frailty is associated with a decreased reserve in specific brain regions, especially cerebellum. Further longitudinal studies are needed to explore if the cerebellum- and noncerebellum-based frailty components reflect a distinctive future risk for developing frailty.

show abstract

Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods

Cited by 111 publications

References 64 publications

Muscle Wasting in Aged, Sarcopenic Rats Is Associated with Enhanced Activity of the Ubiquitin Proteasome Pathway

Muscle Wasting in Aged, Sarcopenic Rats Is Associated with Enhanced Activity of the Ubiquitin Proteasome Pathway

Cellular Degradation Machineries in Age-Related Loss of Muscle Mass (Sarcopenia)

Reduced cerebellar gray matter is a neural signature of physical frailty

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