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Global and tissue-specific aging effects on murine proteomes

ABSTRACT: Maintenance of protein homeostasis degrades with age, contributing to aging-related decline and disease. Previous studies have primarily surveyed transcriptional aging changes. To define the effects of age directly at the protein level, we perform discovery-based proteomics in 10 tissues from 20 C57BL/6J mice, representing both sexes at adult and late midlife ages (8 and 18 months). Consistent with previous studies, age-related changes in protein abundance often have no corresponding transcriptional change. Aging results in increases in immune proteins across all tissues, consistent with a global pattern of immune infiltration with age. Our protein-centric data reveal tissue-specific aging changes with functional consequences, including altered endoplasmic reticulum and protein trafficking in the spleen. We further observe changes in the stoichiometry of protein complexes with important roles in protein homeostasis, including the CCT/TriC complex and large ribosomal subunit. These data provide a foundation for understanding how proteins contribute to systemic aging across tissues.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Devin Schweppe

LAB HEAD: Devin Schweppe

PROVIDER: PXD034029 | Pride | 2023-07-06

REPOSITORIES: Pride

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Project description:Genetic analyses suggest that alterations in gene expression at the molecular and tissue levels can have profound effects on aging for multi-cellular organisms. However, much remains unknown about the normal pattern of genetic changes in different tissues and how these tissues interact during aging. To investigate tissue-specific aging systematically, we measured expression profiles of aging in Drosophila melanogaster in seven tissues representing nervous, muscular, digestive, renal, reproductive, and storage systems. In each tissue, we identified hundreds of age-related genes mostly showing gradual changes of transcript levels with age. Age-relatedgenes showed clear tissue-specific transcriptional patterns; less than 10% of age-related genes in each tissue shared expression patterns with any other tissue; less than 20% of age-related biological processes were shared between tissues. A significant portion of tissue-specific age-related genes are those involved in physiological functions regulated by the corresponding tissue. However, limited overlaps of age-related function groups among tissues particularly those involved in proteasome function suggest some common mechanisms of transcription regulation in aging across tissues. This study defined global, temporal and spatial changes associated withaging at the molecular and tissue levels. Analyses indicated that different tissues might age in different patterns or at different rates. This study addressed comprehensively the relationship of age-related changes among different tissues in one organism, providing a foundation to address tissue-specific regulation in aging. RNA was then amplified by a one-step linear amplification protocol to generate amplified RNA (aRNA). Experiment aRNA refers to amplified RNA from flies of 15, 20, 30, 45 and 60 days old, and reference aRNA refers to amplified RNA from flies of 3 days old, and experiment and reference aRNAs were labeled with fluorescent dye Cy3 and Cy5, respectively. For each tissue, RNA from the corresponding tissue of 3-day old flies was used as the reference RNA and expression profiles at each of the five age-points was measured twice by using independently prepared duplicated samples. Seven types of tissues or organs of the male fly strain w1118 , accessory gland, testis, brain, gut, malpighian tubule, dorsal thoracic muscle and abdominal fat body were hand dissected out of flies at age of 3, 15, 20, 30, 45 and 60 days old. Tissues or organs from four males of the same age were pooled together and used for each RNA sample preparation.

Project description:Genetic analyses suggest that alterations in gene expression at the molecular and tissue levels can have profound effects on aging for multi-cellular organisms. However, much remains unknown about the normal pattern of genetic changes in different tissues and how these tissues interact during aging. To investigate tissue-specific aging systematically, we measured expression profiles of aging in Drosophila melanogaster in seven tissues representing nervous, muscular, digestive, renal, reproductive, and storage systems. In each tissue, we identified hundreds of age-related genes mostly showing gradual changes of transcript levels with age. Age-relatedgenes showed clear tissue-specific transcriptional patterns; less than 10% of age-related genes in each tissue shared expression patterns with any other tissue; less than 20% of age-related biological processes were shared between tissues. A significant portion of tissue-specific age-related genes are those involved in physiological functions regulated by the corresponding tissue. However, limited overlaps of age-related function groups among tissues particularly those involved in proteasome function suggest some common mechanisms of transcription regulation in aging across tissues. This study defined global, temporal and spatial changes associated withaging at the molecular and tissue levels. Analyses indicated that different tissues might age in different patterns or at different rates. This study addressed comprehensively the relationship of age-related changes among different tissues in one organism, providing a foundation to address tissue-specific regulation in aging. RNA was then amplified by a one-step linear amplification protocol to generate amplified RNA (aRNA). Experiment aRNA refers to amplified RNA from flies of 15, 20, 30, 45 and 60 days old, and reference aRNA refers to amplified RNA from flies of 3 days old, and experiment and reference aRNAs were labeled with fluorescent dye Cy3 and Cy5, respectively. For each tissue, RNA from the corresponding tissue of 3-day old flies was used as the reference RNA and expression profiles at each of the five age-points was measured twice by using independently prepared duplicated samples. Keywords: Drosophila melanogaster; Tissue-specific; Brain; Muscle; Gut; Malpighian tubule; Accessory gland; Testis; Adipose tissue; Genome-wide, aging

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Global and tissue-specific aging effects on murine proteomes

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