Age-related changes in muscle ammonia detoxification potential in exhausted rats

Mohan, Parvathi; Reddy, L. Srinivasula; Satyanarayana, Niranjan Raj; Indira, K.

doi:10.3109/13813458709075023

Cited by 5 publications

(6 citation statements)

References 12 publications

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“…Carefully designed and controlled animal aging studies have been instrumental for further identification of the age-related changes in the regulation of ATP and AdNs. Increased AdN degradation in aging skeletal muscle is supported by complementary reports of decreased [ATP] [140][141][142], reductions in the total AdN pool [143,144], and increased formation of purine degradation products such as hypoxanthine [145], and ammonia [146].…”

Section: Adns In Aging-associated Atrophymentioning

confidence: 82%

Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

Miller

Hafen

Brault

2019

IJMS

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Adenine nucleotides (AdNs: ATP, ADP, AMP) are essential biological compounds that facilitate many necessary cellular processes by providing chemical energy, mediating intracellular signaling, and regulating protein metabolism and solubilization. A dramatic reduction in total AdNs is observed in atrophic skeletal muscle across numerous disease states and conditions, such as cancer, diabetes, chronic kidney disease, heart failure, COPD, sepsis, muscular dystrophy, denervation, disuse, and sarcopenia. The reduced AdNs in atrophic skeletal muscle are accompanied by increased expression/activities of AdN degrading enzymes and the accumulation of degradation products (IMP, hypoxanthine, xanthine, uric acid), suggesting that the lower AdN content is largely the result of increased nucleotide degradation. Furthermore, this characteristic decrease of AdNs suggests that increased nucleotide degradation contributes to the general pathophysiology of skeletal muscle atrophy. In view of the numerous energetic, and non-energetic, roles of AdNs in skeletal muscle, investigations into the physiological consequences of AdN degradation may provide valuable insight into the mechanisms of muscle atrophy.

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Section: Adns In Aging-associated Atrophymentioning

confidence: 82%

Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

Miller

Hafen

Brault

2019

IJMS

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“…[31] demonstrated that impaired PI3K/Akt activation directly contributes to the effect of aging on pancreatic acinar cell proliferation. Similarly, Satyanarayana et al [32,33] have revealed that aging-induced muscle atrophy is associated with differences in the regulation of Akt and mTOR. Furthermore, it has been reported that reduced activation of extracellular signal-regulated kinase (ERK) and Akt kinase contributes to lower survival of aged hepatocytes which are more sensitive to H 2 O 2 -induced apoptosis [34,35].…”

Section: Discussionmentioning

confidence: 96%

Inositol pyrophosphates mediate the effects of aging on bone marrow mesenchymal stem cells by inhibiting Akt signaling

et al. 2014

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IntroductionBone marrow-derived mesenchymal stem cells (BM-MSCs) have been proposed as an ideal autologous stem cell source for cell-based therapy for myocardial infarction (MI). However, decreased viability and impaired function of aged MSCs hampered the therapeutic efficacy of engrafted MSCs, and the underlying mechanisms remain unclarified. Here, we investigated the role of inositol phosphates 6 kinase (IP6Ks) inhibition on the therapeutic efficacy of BM-MSCs and its underlying mechanism.MethodsBM-MSCs isolated from young (8-week-old) or aged (18-month-old) donor male C57BL/6 mice, were subjected to hypoxia and serum deprivation (H/SD) injury with or without administration of inositol phosphates 6 kinase (IP6Ks) inhibitor TNP (10 μM). MSC apoptosis induced by H/SD was determined by flow cytometry and TUNEL assays. Protein expressions were evaluated by Western blot assay. Furthermore, the paracrine effects of MSCs were measured by reverse transcriptase–polymerized chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses.ResultsAged BM-MSCs exhibited more Inositol pyrophosphate 7 (IP7) production, compared with young BM-MSCs. Meanwhile, the expression of phospho-Akt (Thr308) was significantly decreased in the aged MSCs, resulting in enhanced Bad activation and decreased Bax/Bcl-2 ratio. Moreover, the apoptosis in aged BM-MSCs was increased, compared with young BM-MSCs. Furthermore, TNP administration significantly inhibited IP7 production and increased the phosphorylation of Akt under both normoxic and hypoxic conditions. Meanwhile, IP6Ks inhibition reduced apoptotic index of aged MSCs, associated with decreased expressions of pro-apoptotic proteins Bax and Bad and increased anti-apoptotic protein Bcl-2. The expressions of angiogenic factors, including VEGF, bFGF, IGF-1 and HGF, were decreased in MSCs from aged mice. In addition, TNP administration enhanced the paracrine efficiency of aged BM-MSCs under normoxic and hypoxic conditions.ConclusionsThis study demonstrates for the first time that IP6Ks and IP7 play critical role in the aging related vulnerability to hypoxic injury and impaired paracrine efficiency of BM-MSCs, which is associated with impaired Akt activation.

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“…This theme captures some of the microbial contributions to aging related inflammation. Studies have reported an increased muscle and blood ammonia content with age, implicating the possibility of elevated purine nucleotide deamination during senescence (Mohan et al 1987). In addition, the microbial ammonia production pathway could contribute to increased ammonia levels in the aged population thereby increasing inflammation.…”

Section: Proinflammatory Activities In Agingmentioning

confidence: 99%

An accurate aging clock developed from the largest dataset of microbial and human gene expression reveals molecular mechanisms of aging

Gopu

Cai

Krishnan

et al. 2020

Preprint

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Accurate measurement of the biological markers of the aging process could provide an “aging clock” measuring predicted longevity and allow for the quantification of the effects of specific lifestyle choices on healthy aging. Using modern machine learning techniques, we demonstrate that chronological age can be predicted accurately from (a) the expression level of human genes in capillary blood, and (b) the expression level of microbial genes in stool samples. The latter uses the largest existing metatranscriptomic dataset, stool samples from 90,303 individuals, and is the highest-performing gut microbiome-based aging model reported to date. Our analysis suggests associations between biological age and lifestyle/health factors, e.g., people on a paleo diet or with IBS tend to be biologically older, and people on a vegetarian diet tend to be biologically younger. We delineate the key pathways of systems-level biological decline based on the age-specific features of our model; targeting these mechanisms can aid in development of new anti-aging therapeutic strategies.

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Age-related changes in muscle ammonia detoxification potential in exhausted rats

Cited by 5 publications

References 12 publications

Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

Inositol pyrophosphates mediate the effects of aging on bone marrow mesenchymal stem cells by inhibiting Akt signaling

An accurate aging clock developed from the largest dataset of microbial and human gene expression reveals molecular mechanisms of aging

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