Growth Differentiation Factor-15 in Immunity and Aging

Overview

Journal Front Aging

Specialty Geriatrics

Date 2022 Jul 13

PMID 35821815

Authors

Brandt D Pence

Affiliations

Soon will be listed here.

Abstract

Aging increases susceptibility to and severity of a variety of chronic and infectious diseases. Underlying this is dysfunction of the immune system, including chronic increases in low-grade inflammation (inflammaging) and age-related immunosuppression (immunosenescence). Growth differentiation factor-15 (GDF-15) is a stress-, infection-, and inflammation-induced cytokine which is increased in aging and suppresses immune responses. This mini review briefly covers existing knowledge on the immunoregulatory and anti-inflammatory roles of GDF-15, as well as its potential importance in aging and immune function.

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References

Pence B, Yarbro J, Emmons R . Growth differentiation factor-15 is associated with age-related monocyte dysfunction. Aging Med (Milton). 2021; 4(1):47-52. PMC: 7954822. DOI: 10.1002/agm2.12128. View

Franceschi C, Campisi J . Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014; 69 Suppl 1:S4-9. DOI: 10.1093/gerona/glu057. View

Baek S, Kim K, Nixon J, Wilson L, Eling T . Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol. 2001; 59(4):901-8. View

Wong C, Goldstein D . Impact of aging on antigen presentation cell function of dendritic cells. Curr Opin Immunol. 2013; 25(4):535-41. PMC: 3775944. DOI: 10.1016/j.coi.2013.05.016. View

Zhang Y, Zhang G, Liu Y, Chen R, Zhao D, McAlister V . GDF15 Regulates Malat-1 Circular RNA and Inactivates NFκB Signaling Leading to Immune Tolerogenic DCs for Preventing Alloimmune Rejection in Heart Transplantation. Front Immunol. 2018; 9:2407. PMC: 6218625. DOI: 10.3389/fimmu.2018.02407. View

Tavenier J, Hartmann Rasmussen L, Andersen A, Houlind M, Langkilde A, Andersen O . Association of GDF15 With Inflammation and Physical Function During Aging and Recovery After Acute Hospitalization: A Longitudinal Study of Older Patients and Age-Matched Controls. J Gerontol A Biol Sci Med Sci. 2021; 76(6):964-974. DOI: 10.1093/gerona/glab011. View

Wischhusen J, Melero I, Fridman W . Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint. Front Immunol. 2020; 11:951. PMC: 7248355. DOI: 10.3389/fimmu.2020.00951. View

Linton P, Thoman M . Immunosenescence in monocytes, macrophages, and dendritic cells: lessons learned from the lung and heart. Immunol Lett. 2014; 162(1 Pt B):290-7. PMC: 4256137. DOI: 10.1016/j.imlet.2014.06.017. View

Pence B, Yarbro J . Classical monocytes maintain ex vivo glycolytic metabolism and early but not later inflammatory responses in older adults. Immun Ageing. 2019; 16:3. PMC: 6348080. DOI: 10.1186/s12979-019-0143-1. View

10.

Tanaka T, Basisty N, Fantoni G, Candia J, Moore A, Biancotto A . Plasma proteomic biomarker signature of age predicts health and life span. Elife. 2020; 9. PMC: 7723412. DOI: 10.7554/eLife.61073. View

11.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

12.

Lee S, Kang S, Choi M, Jung S, Ryu M, Chung H . Growth Differentiation Factor 15 Mediates Systemic Glucose Regulatory Action of T-Helper Type 2 Cytokines. Diabetes. 2017; 66(11):2774-2788. DOI: 10.2337/db17-0333. View

13.

Buldak L, Labuzek K, Buldak R, Kozlowski M, Machnik G, Liber S . Metformin affects macrophages' phenotype and improves the activity of glutathione peroxidase, superoxide dismutase, catalase and decreases malondialdehyde concentration in a partially AMPK-independent manner in LPS-stimulated human.... Pharmacol Rep. 2014; 66(3):418-29. DOI: 10.1016/j.pharep.2013.11.008. View

14.

Kapetanovic R, Bokil N, Sweet M . Innate immune perturbations, accumulating DAMPs and inflammasome dysregulation: A ticking time bomb in ageing. Ageing Res Rev. 2015; 24(Pt A):40-53. DOI: 10.1016/j.arr.2015.02.005. View

15.

Hromas R, Hufford M, Sutton J, Xu D, Li Y, Lu L . PLAB, a novel placental bone morphogenetic protein. Biochim Biophys Acta. 1997; 1354(1):40-4. DOI: 10.1016/s0167-4781(97)00122-x. View

16.

Doerstling S, Hedberg P, Ohrvik J, Leppert J, Henriksen E . Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact. Ups J Med Sci. 2018; 123(2):86-93. PMC: 6055745. DOI: 10.1080/03009734.2018.1460427. View

17.

Jung S, Choi M, Ryu D, Yi H, Lee S, Chang J . Reduced oxidative capacity in macrophages results in systemic insulin resistance. Nat Commun. 2018; 9(1):1551. PMC: 5908799. DOI: 10.1038/s41467-018-03998-z. View

18.

Saeki M, Sekine S, Kato S . Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta. J Biochem. 1997; 122(3):622-6. DOI: 10.1093/oxfordjournals.jbchem.a021798. View

19.

Moon J, Goeminne L, Kim J, Tian J, Kim S, Nga H . Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice. Aging Cell. 2020; 19(8):e13195. PMC: 7431835. DOI: 10.1111/acel.13195. View

20.

Roth P, Junker M, Tritschler I, Mittelbronn M, Dombrowski Y, Breit S . GDF-15 contributes to proliferation and immune escape of malignant gliomas. Clin Cancer Res. 2010; 16(15):3851-9. DOI: 10.1158/1078-0432.CCR-10-0705. View