Proteome analysis in the assessment of ageing

Nkuipou‐Kenfack, Esther; Koeck, Thomas; Mischak, Harald; Pich, Andreas; Schanstra, Joost P.; Zürbig, Petra; Schumacher, Björn

doi:10.1016/j.arr.2014.09.002

Cited by 19 publications

(16 citation statements)

References 147 publications

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“…Indeed, the loss of proteins including mitochondrial proteins during aging has been observed in previous studies [42–44]. Genomic DNA damage, abnormal protein modifications, and enhanced proteolysis are thought to contribute to the loss of proteins in aging brains [42–44]. Interestingly, in this study we have found the selective loss of OSCP closely accompanies CypD upregulation and the depletion of CypD preserves OSCP expression levels during aging.…”

Section: Discussionsupporting

confidence: 79%

“…However, our finding has raised a scientific issue of the regulation of OSCP expression in aging brain. Indeed, the loss of proteins including mitochondrial proteins during aging has been observed in previous studies [42–44]. Genomic DNA damage, abnormal protein modifications, and enhanced proteolysis are thought to contribute to the loss of proteins in aging brains [42–44].…”

Section: Discussionmentioning

confidence: 88%

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Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice

Gauba

Guo

2016

JAD

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Brain aging is the known strongest risk factor for Alzheimer’s disease (AD). In recent years, mitochondrial deficits have been proposed to be a common mechanism linking brain aging to AD. Therefore, to elucidate the causative mechanisms of mitochondrial dysfunction in aging brains is of paramount importance for our understanding of the pathogenesis of AD, in particular its sporadic form. Cyclophilin D (CypD) is a specific mitochondrial protein. Recent studies have shown that F1FO ATP synthase oligomycin sensitivity conferring protein (OSCP) is a binding partner of CypD. The interaction of CypD with OSCP modulates F1FO ATP synthase function and mediates mitochondrial permeability transition pore (mPTP) opening. Here, we have found that increased CypD expression, enhanced CypD/OSCP interaction, and selective loss of OSCP are prominent brain mitochondrial changes in aging mice. Along with these changes, brain mitochondria from the aging mice demonstrated decreased F1FO ATP synthase activity and defective F1FO complex coupling. In contrast, CypD deficient mice exhibited substantially mitigated brain mitochondrial F1FO ATP synthase dysfunction with relatively preserved mitochondrial function during aging. Interestingly, the aging-related OSCP loss was also dramatically attenuated by CypD depletion. Therefore, the simplest interpretation of this study is that CypD promotes F1FO ATP synthase dysfunction and the resultant mitochondrial deficits in aging brains. In addition, in view of CypD and F1FO ATP synthase alterations seen in AD brains, the results further suggest that CypD-mediated F1FO ATP synthase deregulation is a shared mechanism linking mitochondrial deficits in brain aging and AD.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 88%

Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice

Gauba

Guo

2016

JAD

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“…In recent years, with the aggravation of elderly populations, the incidence of age-related chronic diseases is becoming prevalent, which will bring unprecedented challenges to individuals, societies, and their health care systems. Therefore, there is an urgent need to understand physiological aging and achieve "healthy" aging by reducing age-related pathological changes [149]. Recent studies have found that damaged dysfunctional or toxic proteins and silent mutations are the phenotypes of aging, and may also be the causes of related diseases [150].…”

Section: Discussionmentioning

confidence: 99%

Oxidations and amino acid substitutions in urinary proteins are the distinguishing characteristics of aging

Liu

Pan

Hua

et al. 2020

Preprint

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Aging is an inevitable course of life. Additionally, the risk of chronic diseases or cancer increases with age. The comprehensive identification of signs related to aging can be beneficial for the prevention and early diagnosis of geriatric diseases. The comparison of global modifications in the urine proteome is a means of multidimensional information mining. This approach is based on urine, in which changes from whole-body metabolism can accumulate. This study used the urine of healthy people at different ages (22 children, 10 young people, 6 senior people) as the research object and using high-resolution tandem mass spectrometry, label-free quantitation combined with non-limiting modification identification algorithms and random group test, compared the differences in protein chemical modifications among three groups. The results show that multi-sites oxidative modifications and amino acid substitutions are noticeable features that distinguish these three age groups of people. The proportion of multi-site oxidations in urine proteins of senior (29.76%) is significantly higher than the young group (13.71% and 12.97%), which affect the biological processes of various proteins. This study could provide a reference for studies of aging mechanisms and biomarkers of age-related disease.

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“…aging is a complex systemic process and a major limitation in aging research is the scarce knowledge of pathways that derail the normal aging process towards diseaserelated pathologies [40]. Within this context, omics approaches may help to break down and elucidate the cellular and molecular mechanisms of senescence and age-associated processes.…”

Section: Geri-omicsmentioning

confidence: 99%

Analytical tools to assess aging in humans: The rise of geri-omics

Costa

Rocha-Santos

2016

TrAC Trends in Analytical Chemistry

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Population aged 65+ is expected to be over 2.5 times that of the population aged 0-4 by 2050. The onset of age-related ailments, such as neurodegenerative, cardiovascular and respiratory diseases will lead to unprecedented challenges in the health care systems of all countries affected. Yet, despite the acceptance that aging is a natural process, aging research is very much a maturing science. It is currently focused on understanding the physiological changes that take place in "normal" aging and the molecular multimechanistic process that is at the core of senescence. Contributing factors are not fully understood and omics-, namely, transcriptomics, proteomics and metabolomics-are at the forefront of this research. Herein, we overview some of the most recent works focusing on aging through different omics and related bioinformatic tools and discuss how these can contribute for the elucidation of one of the most baffling aspects of human life.

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Proteome analysis in the assessment of ageing

Cited by 19 publications

References 147 publications

Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice

Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice

Oxidations and amino acid substitutions in urinary proteins are the distinguishing characteristics of aging

Analytical tools to assess aging in humans: The rise of geri-omics

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