Growth Differentiation Factor-15 in Immunity and Aging

Pence, Brandt D.

doi:10.3389/fragi.2022.837575

Cited by 28 publications

(20 citation statements)

References 89 publications

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“…GDF15 is a distant member of the transforming growth factor (TGF)‐β superfamily of cytokines. It is released in response to inflammatory stimuli and has an anti‐inflammatory effect (Pence, 2022). It also reduces fat mass by appetite suppression and lipolysis (Fujita et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Late‐life plasma proteins associated with prevalent and incident frailty: A proteomic analysis

Liu,

Austin,

Schrack

et al. 2023

Aging Cell

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Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, proteomic studies of frailty are scarce, and few evaluated prefrailty as a separate state or examined predictors of incident frailty. Using plasma proteins measured by 4955 SOMAmers in the Atherosclerosis Risk in Community study, we identified 134 and 179 proteins cross‐sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p < 1 × 10−5) among 3838 older adults aged ≥65 years, adjusting for demographic and physiologic factors and chronic diseases. Among them, 23 (17%) and 82 (46%) were replicated in the Cardiovascular Health Study using the same models (FDR p < 0.05). Notably, higher odds of prefrailty and frailty were observed with higher levels of growth differentiation factor 15 (GDF15; pprefrailty = 1 × 10−15, pfrailty = 2 × 10−19), transgelin (TAGLN; pprefrailty = 2 × 10−12, pfrailty = 6 × 10−22), and insulin‐like growth factor‐binding protein 2 (IGFBP2; pprefrailty = 5 × 10−15, pfrailty = 1 × 10−15) and with a lower level of growth hormone receptor (GHR, pprefrailty = 3 × 10−16, pfrailty = 2 × 10−18). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 × 10−5). Higher levels of triggering receptor expressed on myeloid cells 1 (TREM1), TAGLN, and heart and adipocyte fatty‐acid binding proteins predicted incident frailty. Differentially regulated proteins were enriched in pathways and upstream regulators related to lipid metabolism, angiogenesis, inflammation, and cell senescence. Our findings provide a set of plasma proteins and biological mechanisms that were dysregulated in both the prodromal and the clinical stage of frailty, offering new insights into frailty etiology and targets for intervention.

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Section: Discussionmentioning

confidence: 99%

Late‐life plasma proteins associated with prevalent and incident frailty: A proteomic analysis

Liu,

Austin,

Schrack

et al. 2023

Aging Cell

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“…It had previously been associated with numerous other conditions like cardiovascular disease, sepsis, cancer, and diabetes [ 50 ]. GDF-15 is known to have immunoregulatory and anti-inflammatory functions, but its exact role in mitochondrial diseases is not well understood [ 51 ].…”

Section: Gdf-15mentioning

confidence: 99%

Biomarkers of mitochondrial disorders

Shayota

2024

Neurotherapeutics

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“…Plasma growth differentiation factor 15 (GDF15) and N terminal pro B type natriuretic peptide (NT proBNP) are biomarker candidates that have yielded promising results as indicators of a range of morbidities. GDF15 is associated with low-grade inflammation and age-related immunosuppression (3). Higher levels of GDF15 have been found, through Mendelian randomisation, to causally associate with increased risk of cardiometabolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction (4).…”

Section: Introductionmentioning

confidence: 99%

DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain

Gadd,

Smith,

Mullin

et al. 2023

Preprint

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Background: Plasma growth differentiation factor 15 (GDF15) and Nterminal proBtype natriuretic peptide (NTproBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NTproBNP may provide new routes for risk stratification. Results: In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NTproBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR < 0.05). Bayesian Epigenome wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NTproBNP, respectively. EpiScores for GDF15 and NTproBNP that were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (Hazard Ratios (HR) range 1.36 to 1.41, PFDR <0.03). The EpiScore for NTproBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7-12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population. Conclusions: EpiScores for serum levels of GDF15 and NtproBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.

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Growth Differentiation Factor-15 in Immunity and Aging

Cited by 28 publications

References 89 publications

Late‐life plasma proteins associated with prevalent and incident frailty: A proteomic analysis

Late‐life plasma proteins associated with prevalent and incident frailty: A proteomic analysis

Biomarkers of mitochondrial disorders

DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain

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