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GIT2 acts as a potential keystone protein in functional hypothalamic networks associated with age-related phenotypic changes in rats.

Chadwick W, Martin B, Chapter MC, Park SS, Wang L, Daimon CM, Brenneman R, Maudsley S - PLoS ONE (2012)

Bottom Line: However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood.Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration.Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process.

View Article: PubMed Central - PubMed

Affiliation: Receptor Pharmacology Unit, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, Maryland, United States of America.

ABSTRACT
The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process.

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KEGG signaling pathway analysis of aging-related hypothalamic proteins.Proteins significantly regulated in middle (M) or old (O) aged animals compared to young (Y) animals were used as input data for KEGG signaling pathway population analysis. (A) Venn diagram analysis of middle-aged (grey line) and old-aged (black line) significantly-regulated KEGG pathways demonstrated 27 common KEGG terms between old and middle-aged tissues. The common (27) significantly populated pathways for middle-aged (grey bars) and old aged (black bars) animals were then rationally clustered into subgroups focused upon disease pathology (B), neurophysiological activity (C), and intermediary cellular signaling activity (D). For each significantly-populated KEGG pathway a ‘hybrid’ score was generated which represents the −log10 of the enrichment probability multiplied with the relative enrichment factor compared to the background proteomic expression.
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pone-0036975-g003: KEGG signaling pathway analysis of aging-related hypothalamic proteins.Proteins significantly regulated in middle (M) or old (O) aged animals compared to young (Y) animals were used as input data for KEGG signaling pathway population analysis. (A) Venn diagram analysis of middle-aged (grey line) and old-aged (black line) significantly-regulated KEGG pathways demonstrated 27 common KEGG terms between old and middle-aged tissues. The common (27) significantly populated pathways for middle-aged (grey bars) and old aged (black bars) animals were then rationally clustered into subgroups focused upon disease pathology (B), neurophysiological activity (C), and intermediary cellular signaling activity (D). For each significantly-populated KEGG pathway a ‘hybrid’ score was generated which represents the −log10 of the enrichment probability multiplied with the relative enrichment factor compared to the background proteomic expression.

Mentions: Clustering of the significantly-regulated hypothalamic proteins from M or O animals resulted in the population of 44 and 56 distinct KEGG pathways, respectively (Tables S4, S5). There were 27 significantly-populated KEGG pathways that were common between the two different age profiles (M/Y and O/Y) (Fig. 3A). These commonly-populated KEGG pathways were then rationally grouped together into sets focusing upon disease pathways (Fig. 3B), neurophysiological architecture (Fig. 3C), and intermediary cell metabolism signaling pathways (Fig. 3D). Among these commonly-regulated KEGG pathways, 22 out of 27 possessed a greater hybrid score (indicating the profundity of KEGG pathway population) within the old animal datasets, demonstrating a strong age-dependent trajectory of these predicted biological functions.


GIT2 acts as a potential keystone protein in functional hypothalamic networks associated with age-related phenotypic changes in rats.

Chadwick W, Martin B, Chapter MC, Park SS, Wang L, Daimon CM, Brenneman R, Maudsley S - PLoS ONE (2012)

KEGG signaling pathway analysis of aging-related hypothalamic proteins.Proteins significantly regulated in middle (M) or old (O) aged animals compared to young (Y) animals were used as input data for KEGG signaling pathway population analysis. (A) Venn diagram analysis of middle-aged (grey line) and old-aged (black line) significantly-regulated KEGG pathways demonstrated 27 common KEGG terms between old and middle-aged tissues. The common (27) significantly populated pathways for middle-aged (grey bars) and old aged (black bars) animals were then rationally clustered into subgroups focused upon disease pathology (B), neurophysiological activity (C), and intermediary cellular signaling activity (D). For each significantly-populated KEGG pathway a ‘hybrid’ score was generated which represents the −log10 of the enrichment probability multiplied with the relative enrichment factor compared to the background proteomic expression.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3351446&req=5

pone-0036975-g003: KEGG signaling pathway analysis of aging-related hypothalamic proteins.Proteins significantly regulated in middle (M) or old (O) aged animals compared to young (Y) animals were used as input data for KEGG signaling pathway population analysis. (A) Venn diagram analysis of middle-aged (grey line) and old-aged (black line) significantly-regulated KEGG pathways demonstrated 27 common KEGG terms between old and middle-aged tissues. The common (27) significantly populated pathways for middle-aged (grey bars) and old aged (black bars) animals were then rationally clustered into subgroups focused upon disease pathology (B), neurophysiological activity (C), and intermediary cellular signaling activity (D). For each significantly-populated KEGG pathway a ‘hybrid’ score was generated which represents the −log10 of the enrichment probability multiplied with the relative enrichment factor compared to the background proteomic expression.
Mentions: Clustering of the significantly-regulated hypothalamic proteins from M or O animals resulted in the population of 44 and 56 distinct KEGG pathways, respectively (Tables S4, S5). There were 27 significantly-populated KEGG pathways that were common between the two different age profiles (M/Y and O/Y) (Fig. 3A). These commonly-populated KEGG pathways were then rationally grouped together into sets focusing upon disease pathways (Fig. 3B), neurophysiological architecture (Fig. 3C), and intermediary cell metabolism signaling pathways (Fig. 3D). Among these commonly-regulated KEGG pathways, 22 out of 27 possessed a greater hybrid score (indicating the profundity of KEGG pathway population) within the old animal datasets, demonstrating a strong age-dependent trajectory of these predicted biological functions.

Bottom Line: However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood.Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration.Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process.

View Article: PubMed Central - PubMed

Affiliation: Receptor Pharmacology Unit, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, Maryland, United States of America.

ABSTRACT
The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process.

Show MeSH