Autologous NK Cells Propagated and Activated Decrease Senescence Markers in Human PBMCs

Overview

Journal Biochem Biophys Rep

Specialty Biochemistry

Date 2022 Nov 17

PMID 36386442

Authors

Nickolas Chelyapov

Toai T Nguyen

Rafael Gonzalez

Affiliations

Soon will be listed here.

Abstract

Aging is a multifactorial process involving many steps including senescence. The immune system plays a critical role in aging where chronic inflammation and senescence has been shown to be detrimental. Natural killer (NK) cells are the predominant innate lymphocyte subset that mediate various responses to include surveillance and elimination of senescent cells. Here, we use autologous propagated and activated NK (aNK) cells from 5 patients to demonstrate that aNK cells decrease senescent cells and immunosenescence in humans based on markers p16 and β-galactosidase. In addition, inflammatory cytokine panel data suggest a role for removal of immunosenescence to reduce the aging-related inflammatory response.

Citing Articles

Senescent T Cells: The Silent Culprit in Acute Myeloid Leukemia Progression?.

Zhang X, Liu L Int J Mol Sci. 2024; 25(23).

PMID: 39684260 PMC: 11641610. DOI: 10.3390/ijms252312550.

Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.

Chen S, Zhu H, Jounaidi Y Signal Transduct Target Ther. 2024; 9(1):302.

PMID: 39511139 PMC: 11544004. DOI: 10.1038/s41392-024-02005-w.

Adoptive NK cell therapy: a potential revolutionary approach in longevity therapeutics.

Deng X, Terunuma H Immun Ageing. 2024; 21(1):43.

PMID: 38926847 PMC: 11201368. DOI: 10.1186/s12979-024-00451-2.

Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics.

Li J, Zhang Y, You Y, Huang Z, Wu L, Liang C Front Immunol. 2024; 15:1360687.

PMID: 38464521 PMC: 10920339. DOI: 10.3389/fimmu.2024.1360687.

Immunomodulatory Activity of the Tyrosine Kinase Inhibitor Dasatinib to Elicit NK Cytotoxicity against Cancer, HIV Infection and Aging.

Rodriguez-Agustin A, Casanova V, Grau-Exposito J, Sanchez-Palomino S, Alcami J, Climent N Pharmaceutics. 2023; 15(3).

PMID: 36986778 PMC: 10055786. DOI: 10.3390/pharmaceutics15030917.

References

Marischen L, Englert A, Schmitt A, Einsele H, Loeffler J . Human NK cells adapt their immune response towards increasing multiplicities of infection of Aspergillus fumigatus. BMC Immunol. 2018; 19(1):39. PMC: 6299526. DOI: 10.1186/s12865-018-0276-6. View

Volpe E, Henriksson J, Wang C, Barbosa F, Zaheer M, Zhang X . Interferon-gamma deficiency protects against aging-related goblet cell loss. Oncotarget. 2016; 7(40):64605-64614. PMC: 5323102. DOI: 10.18632/oncotarget.11872. View

Lowes M, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba L, Haider A . Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008; 128(5):1207-11. DOI: 10.1038/sj.jid.5701213. View

Grievink H, Luisman T, Kluft C, Moerland M, Malone K . Comparison of Three Isolation Techniques for Human Peripheral Blood Mononuclear Cells: Cell Recovery and Viability, Population Composition, and Cell Functionality. Biopreserv Biobank. 2016; 14(5):410-415. DOI: 10.1089/bio.2015.0104. View

Zang J, Ye J, Zhang C, Sha M, Gao J . Senescent hepatocytes enhance natural killer cell activity via the CXCL-10/CXCR3 axis. Exp Ther Med. 2019; 18(5):3845-3852. PMC: 6781833. DOI: 10.3892/etm.2019.8037. View

Yousefzadeh M, Schafer M, Noren Hooten N, Atkinson E, Evans M, Baker D . Circulating levels of monocyte chemoattractant protein-1 as a potential measure of biological age in mice and frailty in humans. Aging Cell. 2018; 17(2). PMC: 5847863. DOI: 10.1111/acel.12706. View

Tang X, Deng B, Zang A, He X, Zhou Y, Wang D . Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial. Front Immunol. 2022; 13:940577. PMC: 9562930. DOI: 10.3389/fimmu.2022.940577. View

Langhi Prata L, Ovsyannikova I, Tchkonia T, Kirkland J . Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Semin Immunol. 2019; 40:101275. PMC: 7061456. DOI: 10.1016/j.smim.2019.04.003. View

Yang W, Yao Y, Yang Y, Lu F, Li L, Wang Y . Differential modulation by IL-17A of Cholangitis versus Colitis in IL-2Rα deleted mice. PLoS One. 2014; 9(8):e105351. PMC: 4136813. DOI: 10.1371/journal.pone.0105351. View

10.

Yousefzadeh M, Flores R, Zhu Y, Schmiechen Z, Brooks R, Trussoni C . An aged immune system drives senescence and ageing of solid organs. Nature. 2021; 594(7861):100-105. PMC: 8684299. DOI: 10.1038/s41586-021-03547-7. View

11.

Bruunsgaard H, Skinhoj P, Pedersen A, Schroll M, Pedersen B . Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis. Clin Exp Immunol. 2000; 121(2):255-60. PMC: 1905691. DOI: 10.1046/j.1365-2249.2000.01281.x. View

12.

He S, Sharpless N . Senescence in Health and Disease. Cell. 2017; 169(6):1000-1011. PMC: 5643029. DOI: 10.1016/j.cell.2017.05.015. View

13.

Baker D, Wijshake T, Tchkonia T, LeBrasseur N, Childs B, van de Sluis B . Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011; 479(7372):232-6. PMC: 3468323. DOI: 10.1038/nature10600. View

14.

Shanmugham L, Petrarca C, Castellani M, Frydas S, Vecchiet J, Conti P . Rantes potentiates human macrophage aggregation and activation responses to calcium ionophore (A23187) and activates arachidonic acid pathways. J Biol Regul Homeost Agents. 2007; 20(1-2):15-23. View

15.

Kundu S, Gurney M, ODwyer M . Generating natural killer cells for adoptive transfer: expanding horizons. Cytotherapy. 2021; 23(7):559-566. DOI: 10.1016/j.jcyt.2020.12.002. View

16.

Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen A, Skinhoj P, Pedersen B . A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci. 1999; 54(7):M357-64. DOI: 10.1093/gerona/54.7.m357. View

17.

Budamagunta V, Manohar-Sindhu S, Yang Y, He Y, Traktuev D, Foster T . Senescence-associated hyper-activation to inflammatory stimuli . Aging (Albany NY). 2021; 13(15):19088-19107. PMC: 8386536. DOI: 10.18632/aging.203396. View

18.

Kale A, Sharma A, Stolzing A, Desprez P, Campisi J . Role of immune cells in the removal of deleterious senescent cells. Immun Ageing. 2020; 17:16. PMC: 7271494. DOI: 10.1186/s12979-020-00187-9. View

19.

Krizhanovsky V, Yon M, Dickins R, Hearn S, Simon J, Miething C . Senescence of activated stellate cells limits liver fibrosis. Cell. 2008; 134(4):657-67. PMC: 3073300. DOI: 10.1016/j.cell.2008.06.049. View

20.

Liochev S . Which Is the Most Significant Cause of Aging?. Antioxidants (Basel). 2016; 4(4):793-810. PMC: 4712935. DOI: 10.3390/antiox4040793. View