The Human Muscle Proteome in Aging

Gelfi, Cecilia; Viganò, Adriano; Ripamonti, M.; Pontoglio, Alessandro; Begum, Shajna; Pellegrino, Maria Antonietta; Grassi, Bruno; Bottinelli, Roberto; Wait, Robin; Cerretelli, Paolo

doi:10.1021/pr050414x

Cited by 134 publications

(183 citation statements)

References 45 publications

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“…Following separation by standard 2-DE, the abundance of key mitochondrial markers, such as ATP synthase and isocitrate dehydrogenase, was increased in the DT fraction. This would agree with an age-related shift to more oxidative metabolism in a slower-twitching fibre population [13][14][15]. Differential effects on individual protein spots representing muscle creatine kinase and prohibitin indicate altered post-translational modifications, such as phosphorylation patterns, in these proteins during muscle aging [42].…”

Section: Discussionsupporting

confidence: 68%

“…Several mass spectrometry-based proteomic studies have investigated changes in the protein complement of aging skeletal muscles over the last few years, as reviewed by Doran et al [13]. These proteomic profiling studies have focused on crude soluble extracts and have shown that muscle aging is associated with altered expression levels of many key contractile proteins, regulatory elements, ion handling proteins, metabolic enzymes and mediators of the cellular stress response [14][15][16][17][18][19][20]. The proteomic finding of a drastically decreased density and reduced enzymatic activity of certain glycolytic enzymes in senescent fibres [21] is in agreement with the idea of a fast-to-slow transformation process during aging [13].…”

Section: Introductionmentioning

confidence: 99%

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DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

Donoghue

Staunton

Mullen

et al. 2010

Journal of Proteomics

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Contractile weakness and loss of muscle mass are critical features of the aging process in mammalians. Age-related fibre wasting has a profound effect on muscle metabolism, fibre type distribution and the overall physiological integrity of the neuromuscular system. This study has used mass spectrometry-based proteomics to investigate the fate of the aging rat muscle proteome. Using nonionic detergent phase extraction, this report shows that the aged gastrocnemius muscle exhibits a generally perturbed protein expression pattern in both the detergent-extracted fraction and the aqueous protein complement from senescent muscle tissue. In the detergent-extracted fraction, the expression of ATP synthase, isocitrate dehydrogenase, enolase, tropomyosin and beta-actin was increased. Different isoforms of creatine kinase and prohibitin showed differential changes. In the aqueous fraction, malate dehydrogenase, sulfotransferase, triosephosphate isomerase, aldolase, cofilin-2 and lactate dehydrogenase showed increased levels. Interestingly, differential effects on dissimilar 2-D spots of the same protein species were shown for Cu/Zn superoxide dismutase, albumin, annexin A4 and phosphoglycolate phosphatase. Mitochondrial Hsp60, Hsp71 and nucleoside diphosphate kinase B exhibited a reduced abundance in aged muscle. The majority of altered proteins were found to be involved in mitochondrial metabolism, glycolysis, metabolic transportation, regulatory processes, the cellular stress response, detoxification mechanisms and muscle contraction.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

Donoghue

Staunton

Mullen

et al. 2010

Journal of Proteomics

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“…ATP synthase expression also increased with advancing age in the trophocytes and fat cells of workers. Previous studies have reported similar findings, showing that ATP synthase expression increases with advancing age in the brains and muscle of rats (Nicoletti et al 1995;Chang et al 2007;Doran et al 2008;Donoghue et al 2010), and in muscle of humans (Gelfi et al 2006). Although ND1 and ATP synthase expression measured in absolute terms increased with advancing age in the trophocytes and fat cells of workers, the relative expression of ND1 and ATP synthase normalized to mitochondrial density and VDAC1 was not significantly different.…”

Section: δψMsupporting

confidence: 73%

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

Chuang

Hsu

2012

AGE

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Trophocytes and fat cells in honeybees (Apis mellifera) have served as targets for cellular senescence studies, but mitochondrial energy utilization with advancing age in workers is unknown. In this study, mitochondrial energy utilization was evaluated in the trophocytes and fat cells of young and old workers reared in a field hive. The results showed that (1) mitochondrial density increased with advancing age; (2) mitochondrial membrane potential (ΔΨm), nicotinamide adenine dinucleotide oxidized form (NAD + ) concentration, adenosine triphosphate (ATP) concentration, and NAD + /nicotinamide adenine dinucleotide reduced form (NADH) ratio decreased with advancing age; and (3) the expression of NADH dehydrogenase 1 (ND1), ATP synthase, and voltage-dependent anion channel 1 (VDAC1) increased with advancing age, whereas ND1 and ATP synthase did not differ with advancing age after normalization to mitochondrial density and VDAC1. These results show that the trophocytes and fat cells of young workers have higher mitochondrial energy utilization efficiency than those of old workers and that aging results in a decline in mitochondrial energy utilization in the trophocytes and fat cells of worker honeybees.

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“…The proteomic profiling of crude soluble extracts has revealed a severely perturbed protein expression pattern in aged muscles involving enzymes of various metabolic pathways, regulatory components of ion homeostasis and elements of the cellular stress response (Piec et al, 2005;Gelfi et al, 2006;O'Connell et al, 2007;Doran et al, 2008;Lombardi et al, 2009;Capitanio et al, 2009). Altered post-translational modifications affecting tyrosine nitration, tyrosine/threonine phosphorylation and N-glycosylation were recently documented to occur to a large extent during biological aging of skeletal muscle fibres (Kanski et al, 2005;Gannon et al, 2008;O'Connell et al, 2008b).…”

Section: Introductionmentioning

confidence: 99%

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age

Gannon

Doran

Kirwan

et al. 2009

European Journal of Cell Biology

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The age-dependent decline in skeletal muscle mass and function is believed to be due to a multi-factorial pathology and represents a major factor that blocks healthy aging by increasing physical disability, frailty and loss of independence in the elderly. This study has focused on the comparative proteomic analysis of contractile elements and revealed that the most striking age-related changes seem to occur in the protein family representing myosin light chains (MLCs). Comparative screening of total muscle extracts suggests a fast-to-slow transition in the aged MLC population. The mass spectrometric analysis of the myofibril-enriched fraction identified the MLC2 isoform of the slow-type MLC as the contractile protein with the most drastically changed expression during aging. Immunoblotting confirmed an increased abundance of slow MLC2, concomitant with a switch in fast versus slow myosin heavy chains. Staining of two-dimensional gels of crude extracts with the phospho-specific fluorescent dye ProQ-Diamond identified the increased MLC2 spot as a muscle protein with a drastically enhanced phosphorylation level in aged fibres. Comparative immunofluorescence microscopy, using antibodies to fast and slow myosin isoforms, confirmed a fast-to-slow transformation process during muscle aging. Interestingly, the dramatic increase in slow MLC2 expression was restricted to individual senescent fibres. These findings agree with the idea that aged skeletal muscles undergo a shift to more aerobic-oxidative metabolism in a slower-twitching fibre population and suggest the slow MLC2 isoform as a potential biomarker for fibre type shifting in sarcopenia of old age.

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The Human Muscle Proteome in Aging

Cited by 134 publications

References 45 publications

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age

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