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. 2021 Oct;43(5):2183-2203.
doi: 10.1007/s11357-021-00454-7. Epub 2021 Oct 4.

Oklahoma Nathan Shock Aging Center - assessing the basic biology of aging from genetics to protein and function

Holly Van Remmen  1   2 , Willard M Freeman  3   4 , Benjamin F Miller  5   3 , Michael Kinter  5 , Jonathan D Wren  4 , Ann Chiao  5 , Rheal A Towner  6 , Timothy A Snider  7 , William E Sonntag  3 , Arlan Richardson  3   8
Affiliations

Oklahoma Nathan Shock Aging Center - assessing the basic biology of aging from genetics to protein and function

Holly Van Remmen et al. Geroscience. 2021 Oct.

Abstract

The Oklahoma Shock Nathan Shock Center is designed to deliver unique, innovative services that are not currently available at most institutions. The focus of the Center is on geroscience and the development of careers of young investigators. Pilot grants are provided through the Research Development Core to junior investigators studying aging/geroscience throughout the USA. However, the services of our Center are available to the entire research community studying aging and geroscience. The Oklahoma Nathan Shock Center provides researchers with unique services through four research cores. The Multiplexing Protein Analysis Core uses the latest mass spectrometry technology to simultaneously measure the levels, synthesis, and turnover of hundreds of proteins associated with pathways of importance to aging, e.g., metabolism, antioxidant defense system, proteostasis, and mitochondria function. The Genomic Sciences Core uses novel next-generation sequencing that allows investigators to study the effect of age, or anti-aging manipulations, on DNA methylation, mitochondrial genome heteroplasmy, and the transcriptome of single cells. The Geroscience Redox Biology Core provides investigators with a comprehensive state-of-the-art assessment of the oxidative stress status of a cell, e.g., measures of oxidative damage and redox couples, which are important in aging as well as many major age-related diseases as well as assays of mitochondrial function. The GeroInformatics Core provides investigators assistance with data analysis, which includes both statistical support as well as analysis of large datasets. The Core also has developed number of unique software packages to help with interpretation of results and discovery of new leads relevant to aging. In addition, the Geropathology Research Resource in the Program Enhancement Core provides investigators with pathological assessments of mice using the recently developed Geropathology Grading Platform.

Keywords: Genomic Sciences Core; Geropathology Grading Platform; Geroscience.

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Figures

Fig. 1
Fig. 1
LC-tandem MS analysis of a whole homogenate from Drosophila. A The raw LC-tandem MS data showing the detection of the 3 peptides in scheduled time windows at characteristic retention times. B and C The raw data are analyzed with the program Pinpoint, which finds and integrates the chromatographic peaks via the overlap of the selected reactions. Only 2 peptides are shown because of space. D The amount of each protein is determined by normalizing to a known amount of bovine serum albumin added to the sample as a non-endogenous internal standard. It is notable that the 50% decrease in catalase abundance expected in Drosophila heterozygous for catalase is observed
Fig. 2
Fig. 2
The ability of targeted quantitative proteomics to interrogate pathways. The levels of proteins involved in glycolysis, fatty acid metabolism, the Krebs cycle, and mitochondrial function are shown for skeletal muscle from 10-month-old wild type and Sod1−/− mice. Red bars represent increased expression, blue bars represent decreased expression, and black bars represent non-significant changes in proteins in Sod1−/− mice compared to WT mice. Data were taken from Sataranatarajan et al. [58]
Fig. 3
Fig. 3
Feasibility of measuring protein synthesis rates of individual proteins in skeletal muscle. Normalized (Log2) fold change data are presented from control male and female HET3 mice treated with rapamycin (Rap) or rapamycin plus metformin (Rap + Met). These data were obtained using a time course approach with three mice for time point and five time points. Using GO terms, we separate by cellular compartment (A and B), mitochondrial compartment (C and D) and mitochondrial complex (E and F). Note, there are differences between treatments and relative changes between sexes
Fig. 4
Fig. 4
Levels of methylation and hydroxymethylation in the genome of the hippocampus. DNA isolated from the hippocampus from mice was analyzed for methylation of the traditional bisulfite sequencing and oxBOCS. A Data showing the 5mC and 5hmC contend of DNA isolated from brain. Approximately 25% of the methylation that is normally identified as 5mC is 5hmC. B Data showing a region of the genome where bisulfite sequencing gives an incorrect analysis of DNA modifications on a base-by-base basis
Fig. 5
Fig. 5
Example of mtDNA heteroplasmy. Muscle tissue from young (8 months) wild type (WT, blue), old (27 months) WT (red), and young (8 months) Sod1−/− (KO, green) mice was analyzed for mtDNA mutations using next-generation-sequencing. Mutation locations and frequencies are shown in the circos plot for each group. More heteroplasmic sites were found in old WT and KO mice than young WT (inset, ANOVA, SNK *p < 0.05, n = 5–8 group)
Fig. 6
Fig. 6
Effect of age on the levels of oxidative damage in liver tissue. The levels of lipid peroxidation (isoprostanes) and protein oxidation (carbonyls) were measured in liver tissue from 4- to 6-month-old (blue bars) and 22- to 24-month-old (red bars) rats. Data taken from Ward et al. [75] and Chaudhuri et al. [6]
Fig. 7
Fig. 7
Measurement of free radical levels in vivo. Levels of free radicals were measured is skeletal muscle from wild type (WT), Sod−/− (KO), and SynTgSod−/− (SYN) mice. Free radical maps (red-false-coloring) (ii) overlaid on top of MR images for WT (A) and KO (B) mice are shown. The quantitative levels of free radicals (C), as measured by a percent change in T1 relaxation differences. Free radical levels were found to significantly increase in KO mice compared to WT or SynTgSod−/− (SYN) mice, which have Sod1 expressed in the neurons of Sod1−/− mice. Data taken from Ahn et al. [1]
Fig. 8
Fig. 8
Protein–protein interactions shared by known members of the BCL-2 family that can overcome cellular senescence. The size of the node correlates with the number of connections in the network. Yellow denotes known apoptotic proteins and the white nodes are highly connected on multiple omics levels. The arrow points to the node for HIF1A. Data from Zhu et al. [80]
Fig. 9
Fig. 9
Algorithmic analysis of the scientific literature. a Identifying which concepts/entities (B) connect two other concepts (A and C) in MEDLINE. b Identifying implied relationships by finding and assessing the strength of all A–B and B–C connections. c Visualizing how entities/concepts are connected in the literature
Fig. 10
Fig. 10
Geropathology analysis of wild type and Sod1−/− mice. Whole body geropathology composite scores are shown for male and female wild type (blue bars) and Sod1−/− (red bars) mice at 9 to 10 months of age. Data taken from Snider et al. [61]
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