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Plasma biomarkers of mouse aging.

ABSTRACT: Normal aging is accompanied by a series of physiological changes such as gray hair, cataracts, reduced immunity, and increased susceptibility to disease. To identify novel biomarkers of normal aging, we analyzed plasma proteins of male mice longitudinally from 2 to 19 months of age. Plasma proteins were analyzed by two-dimensional gel electrophoresis and identified using mass spectrometry (MS), MS/MS and liquid chromatography MS/MS. We found that many plasma proteins exist as multiple isoforms with different masses and/or charges. Thirty-nine protein spots (corresponding to six distinct proteins) have been identified, 13 of which exhibited significant changes with age. For example, several proteins increased significantly during aging including one isoform of transthyretin, two isoforms of haptoglobin, and three isoforms of immunoglobulin kappa chain. Conversely, several proteins decreased significantly during aging including peroxiredoxin-2, serum amyloid protein A-1, and five isoforms of albumin. Identification of these proteins provides new biomarkers of normal aging in mice. If validated in humans, these biomarkers may facilitate therapeutic interventions to identify premature aging, delay aging, and/or improve healthspan of the elderly.

SUBMITTER: Ding J

PROVIDER: S-EPMC3168609 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Plasma biomarkers of mouse aging.

Ding Juan J Kopchick John J JJ

Age (Dordrecht, Netherlands) 20100915 3

Normal aging is accompanied by a series of physiological changes such as gray hair, cataracts, reduced immunity, and increased susceptibility to disease. To identify novel biomarkers of normal aging, we analyzed plasma proteins of male mice longitudinally from 2 to 19 months of age. Plasma proteins were analyzed by two-dimensional gel electrophoresis and identified using mass spectrometry (MS), MS/MS and liquid chromatography MS/MS. We found that many plasma proteins exist as multiple isoforms w ...[more]

PMID: 20842533

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Project description:Hyposalivation is a common complaint among the elderly, but no established treatment prevents age-induced hyposalivation. Platelet derivatives such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and plasma rich in growth factor (PRGF), are used widely in different areas of regenerative medicine to enhance the wound healing processes. This study examined whether the local injection of the supernatant of activated PRP (saPRP) into the salivary gland (SG) could help prevent aging-induced SG dysfunction and explored the mechanisms responsible for the protective effects on the SG hypofunction. The platelets were separated from the blood of male SD rats (220 ± 20 g). saPRP was manufactured by removing the fibrin clot after activating platelet with calcium ionophore 10 μM (A23187). The total protein and TGF-β1 levels were significantly higher in saPRP than in PRP. Human salivary gland epithelial cell(hSGEC) was treated with saPRP or PRP after senescence through irradiation. The significant proliferation of hSGEC was observed in saPRP treated group compared to irradiation only group and irradiation + PRP group. Cellular senescence, apoptosis, and inflammation significantly reduced in saPRP group. The SG function and structural tissue remodeling by the saPRP were investigated with naturally aged mice. The mice were divided into three groups: 3 months old (3 M), 22 months old (22 M), and 22 months old treated with saPRP (22 M + saPRP). Salivary flow rate and lag time were significantly improved in 22 M + saPRP group compared to 22 M group. The histologic examinations showed the significant proliferation of acinar cell in 22 M + saPRP group. The decrease of senescence, apoptosis, and inflammation observed by western blot in 22 M + saPRP group. The saPRP induced the proliferation of hSGECs, leading to a significant decrease in cellular senescence via decrease inflammation and apoptosis, in vitro. Moreover, the acini cells of the salivary gland were regenerated, and the salivary function increased in aged mice. These results showed that saPRP could be a treatment agent against aging-induced SG dysfunction.

Project description:BackgroundWith the increase of age, multiple physiological functions of people begin gradually degenerating. Regardless of natural aging or pathological aging, the decline in cognitive function is one of the most obvious features in the process of brain aging. Brain aging is a key factor for several neuropsychiatric disorders and for most neurodegenerative diseases characterized by onset typically occurring late in life and with worsening of symptoms over time. Therefore, the early prevention and intervention of aging progression are particularly important. Since there is no unified conclusion about the plasma diagnostic biomarkers of brain aging, this paper innovatively employed the combined multi-omics analysis to delineate the plasma markers of brain aging.MethodsIn order to search for specific aging markers in plasma during cerebral cortex aging, we used multi-omics analysis to screen out differential genes/proteins by integrating two prefrontal cortex (PFC) single-nucleus transcriptome sequencing (snRNA-seq) datasets and one plasma proteome sequencing datasets. Then plasma samples were collected from 20 young people and 20 elder people to verify the selected differential genes/proteins with ELISA assay.ResultsWe first integrated snRNA-seq data of the post-mortem human PFC and generated profiles of 65,064 nuclei from 14 subjects across adult (44-58 years), early-aging (69-79 years), and late-aging (85-94 years) stages. Seven major cell types were classified based on established markers, including oligodendrocyte, excitatory neurons, oligodendrocyte progenitor cells, astrocytes, microglia, inhibitory neurons, and endotheliocytes. A total of 93 cell-specific genes were identified to be significantly associated with age. Afterward, plasma proteomics data from 2,925 plasma proteins across 4,263 young adults to nonagenarians (18-95 years old) were combined with the outcomes from snRNA-seq data to obtain 12 differential genes/proteins (GPC5, CA10, DGKB, ST6GALNAC5, DSCAM, IL1RAPL2, TMEM132C, VCAN, APOE, PYH1R, CNTN2, SPOCK3). Finally, we verified the 12 differential genes by ELISA and found that the expression trends of five biomarkers (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) were correlated with brain aging.ConclusionFive differentially expressed proteins (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) can be considered as one of the screening indicators of brain aging, and provide a scientific basis for clinical diagnosis and intervention.

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Plasma biomarkers of mouse aging.

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Plasma biomarkers of mouse aging.

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