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. 2024 Feb 12;36(1):36.
doi: 10.1007/s40520-023-02654-x.

Dysregulation of acyl carnitines, pentose phosphate pathway and arginine and ornithine metabolism are associated with decline in intrinsic capacity in Chinese older adults

Yiming Pan  1   2 , Yun Li  3   4 , Jagadish K Chhetri  1   5   2 , Pan Liu  1   2 , Bowen Li  6 , Zuyun Liu  7 , Guanghou Shui  8 , Lina Ma  9   10
Affiliations

Dysregulation of acyl carnitines, pentose phosphate pathway and arginine and ornithine metabolism are associated with decline in intrinsic capacity in Chinese older adults

Yiming Pan et al. Aging Clin Exp Res. .

Abstract

Background: Intrinsic capacity is the combination of individual physical and mental abilities, reflecting the aging degree of the older adults. However, the mechanisms and metabolic characteristics of the decline in intrinsic capacity are still unclear.

Aims: To identify metabolic signatures and associated pathways of decline in intrinsic capacity based on the metabolite features.

Methods: We recruited 70 participants aged 77.19 ± 8.31 years. The five domains of intrinsic capacity were assessed by Short Physical Performance Battery (for mobility), Montreal cognition assessment (for cognition), 30-Item Geriatric Depression Scale (for psychology), self-reported hearing/visual impairment (for sensory) and Nutritional risk screening (for vitality), respectively. The serum samples of participants were analyzed by liquid chromatography-mass spectrometry-based metabolomics, followed by metabolite set enrichment analysis and metabolic pathway analysis.

Results: There were 50 participants with a decline in intrinsic capacity in at least one of the domains. A total of 349 metabolites were identified from their serum samples. Overall, 24 differential metabolites, 5 metabolite sets and 13 pathways were associated with the decline in intrinsic capacity.

Discussion: Our results indicated that decline in intrinsic capacity had unique metabolomic profiles.

Conclusion: The specific change of acyl carnitines was observed to be a feature of decline in intrinsic capacity. Dysregulation of the pentose phosphate pathway and of arginine and ornithine metabolism was strongly associated with the decline in intrinsic capacity.

Keywords: Aging; Functional decline; Intrinsic capacity; Metabolomics.

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Conflict of interest statement

Author Bowen Li is employed by the LipidALL Technologies Company Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic diagram of the study protocol. Gather clinical information, perform intrinsic capacity (IC) assessment on all participants, and collect blood for untargeted metabolomics analysis and laboratory tests. Abbreviations: LC–MS, liquid chromatography-mass spectrometry; SPPB, short physical performance battery; MoCA, Montreal cognition assessment; GDS, geriatric depression scale; NRS, nutritional risk screening
Fig. 2
Fig. 2
A Pearson correlation analysis between intrinsic capacity (IC) score and age. B OPLS-DA score plots of the decline in IC group and control. C OPLS-DA score plots of the decline in mobility group and control. D OPLS-DA score plots of the decline in cognition group and control. E OPLS-DA score plots of the decline in psychology group and control. F OPLS-DA score plots of the decline in sensory group and control. IC intrinsic capacity, OPLS-DA orthogonal partial least squares discriminant analysis
Fig. 3
Fig. 3
Heat map of Spearman correlation analysis of metabolites associated with intrinsic capacity (IC) score, SPPB, MoCA or GDS-30. The metabolites displayed were those with p < 0.05 and absolute value of Spearman rho > 0.3. Negative and positive correlations are shown in blue and red ranging from − 1.0 to 1.0. IC intrinsic capacity, SPPB short physical performance battery, MoCA Montreal cognition assessment, GDS geriatric depression scale
Fig. 4
Fig. 4
Metabolomics changes and possible mechanism of intrinsic capacity (IC) decline. Up-regulation of certain acyl carnitines is characteristic of IC (especially mobility and cognition) decline; RNR up regulation and PPP disorder are features of IC (especially mobility) decline; urea cycle disturbances are features of IC (especially mobility and cognition) decline; imbalance of purine metabolism is characteristic of decline in psychology; metabolomics signature of sensory and vitality domains was unclear. IC intrinsic capacity, RNR reduced nicotinamide riboside, NR nicotinamide riboside, NAD +  nicotinamide adenine dinucleotide, NADH reduced nicotinamide adenine dinucleotide, NADP +  nicotinamide adenine dinucleotide phosphate, NADPH reduced nicotinamide adenine dinucleotide phosphate, PPP pentose phosphate pathway
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