Cellular Senescence is a Key Mediator of Lung Aging and Susceptibility to Infection

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Sep 19

PMID 36119079

Authors

Blake L Torrance

Laura Haynes

Affiliations

Soon will be listed here.

Abstract

Aging results in systemic changes that leave older adults at much higher risk for adverse outcomes following respiratory infections. Much work has been done over the years to characterize and describe the varied changes that occur with aging from the molecular/cellular up to the organismal level. In recent years, the systemic accumulation of senescent cells has emerged as a key mediator of many age-related declines and diseases of aging. Many of these age-related changes can impair the normal function of the respiratory system and its capability to respond appropriately to potential pathogens that are encountered daily. In this review, we aim to establish the effects of cellular senescence on the disruption of normal lung function with aging and describe how these effects compound to leave an aged respiratory system at great risk when exposed to a pathogen. We will also discuss the role cellular senescence may play in the inability of most vaccines to confer protection against respiratory infections when administered to older adults. We posit that cellular senescence may be the point of convergence of many age-related immunological declines. Enhanced investigation into this area could provide much needed insight to understand the aging immune system and how to effectively ameliorate responses to pathogens that continue to disproportionately harm this vulnerable population.

Citing Articles

Ageing results in an exacerbated inflammatory response to LPS by resident lung cells.

Diaz-Nicieza C, Sahyoun L, Michalaki C, Johansson C, Culley F Immun Ageing. 2024; 21(1):62.

PMID: 39261941 PMC: 11391591. DOI: 10.1186/s12979-024-00467-8.

The emerging links between immunosenescence in innate immune system and neurocryptococcosis.

Soraci L, Beccacece A, Princiotto M, Villalta Savedra E, Gambuzza M, Aguennouz M Front Immunol. 2024; 15:1410090.

PMID: 39229268 PMC: 11369721. DOI: 10.3389/fimmu.2024.1410090.

A genomic perspective of the aging human and mouse lung with a focus on immune response and cellular senescence.

He M, Borlak J Immun Ageing. 2023; 20(1):58.

PMID: 37932771 PMC: 10626779. DOI: 10.1186/s12979-023-00373-5.

Respiratory Comorbidities Associated with Bronchiectasis in Patients with Common Variable Immunodeficiency in the USIDNET Registry.

Correa-Jimenez O, Restrepo-Gualteros S, Nino G, Cunningham-Rundles C, Sullivan K, Fuleihan R J Clin Immunol. 2023; 43(8):2208-2220.

PMID: 37932514 PMC: 11310578. DOI: 10.1007/s10875-023-01593-6.

Efficacy and Safety of Vaccinations in Geriatric Patients: A Literature Review.

Ciarambino T, Crispino P, Buono P, Giordano V, Trama U, Iodice V Vaccines (Basel). 2023; 11(9).

PMID: 37766089 PMC: 10537287. DOI: 10.3390/vaccines11091412.

References

Yousefzadeh M, Zhu Y, McGowan S, Angelini L, Fuhrmann-Stroissnigg H, Xu M . Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018; 36:18-28. PMC: 6197652. DOI: 10.1016/j.ebiom.2018.09.015. View

Donaldson G, Seemungal T, Patel I, Bhowmik A, Wilkinson T, Hurst J . Airway and systemic inflammation and decline in lung function in patients with COPD. Chest. 2005; 128(4):1995-2004. PMC: 7172405. DOI: 10.1378/chest.128.4.1995. View

Frasca D, Landin A, Lechner S, Ryan J, Schwartz R, Riley R . Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J Immunol. 2008; 180(8):5283-90. DOI: 10.4049/jimmunol.180.8.5283. View

Alcorta D, Xiong Y, Phelps D, Hannon G, Beach D, Barrett J . Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci U S A. 1996; 93(24):13742-7. PMC: 19411. DOI: 10.1073/pnas.93.24.13742. View

Schneider C, Nobs S, Kurrer M, Rehrauer H, Thiele C, Kopf M . Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat Immunol. 2014; 15(11):1026-37. DOI: 10.1038/ni.3005. View

Chang Y, Kim H, Albacker L, Baumgarth N, McKenzie A, Smith D . Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol. 2011; 12(7):631-8. PMC: 3417123. DOI: 10.1038/ni.2045. View

Silva L, Lourenco J, Silva K, Santana F, Kohler J, Moreira A . Th17/Treg imbalance in COPD development: suppressors of cytokine signaling and signal transducers and activators of transcription proteins. Sci Rep. 2020; 10(1):15287. PMC: 7499180. DOI: 10.1038/s41598-020-72305-y. View

Wang B, Wang L, Gasek N, Zhou Y, Kim T, Guo C . An inducible -Cre mouse model to monitor and manipulate -highly-expressing senescent cells . Nat Aging. 2022; 1(10):962-973. PMC: 8746571. DOI: 10.1038/s43587-021-00107-6. View

Silverman E, Chapman H, Drazen J, Weiss S, Rosner B, Campbell E . Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis. Am J Respir Crit Care Med. 1998; 157(6 Pt 1):1770-8. DOI: 10.1164/ajrccm.157.6.9706014. View

10.

Khosla S, Farr J, Tchkonia T, Kirkland J . The role of cellular senescence in ageing and endocrine disease. Nat Rev Endocrinol. 2020; 16(5):263-275. PMC: 7227781. DOI: 10.1038/s41574-020-0335-y. View

11.

Zacca E, Crespo M, Acland R, Roselli E, Nunez N, Maccioni M . Aging Impairs the Ability of Conventional Dendritic Cells to Cross-Prime CD8+ T Cells upon Stimulation with a TLR7 Ligand. PLoS One. 2015; 10(10):e0140672. PMC: 4608578. DOI: 10.1371/journal.pone.0140672. View

12.

Zhu L, Hua F, Ding W, Ding K, Zhang Y, Xu C . The correlation between the Th17/Treg cell balance and bone health. Immun Ageing. 2020; 17:30. PMC: 7557094. DOI: 10.1186/s12979-020-00202-z. View

13.

Salminen A, Kaarniranta K, Kauppinen A . Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging (Albany NY). 2012; 4(3):166-75. PMC: 3348477. DOI: 10.18632/aging.100444. View

14.

Lefebvre J, Lorenzo E, Masters A, Hopkins J, Eaton S, Smiley S . Vaccine efficacy and T helper cell differentiation change with aging. Oncotarget. 2016; 7(23):33581-94. PMC: 5085104. DOI: 10.18632/oncotarget.9254. View

15.

Li G, Smithey M, Rudd B, Nikolich-Zugich J . Age-associated alterations in CD8α+ dendritic cells impair CD8 T-cell expansion in response to an intracellular bacterium. Aging Cell. 2012; 11(6):968-77. PMC: 3533767. DOI: 10.1111/j.1474-9726.2012.00867.x. View

16.

Brandsma C, de Vries M, Costa R, Woldhuis R, Konigshoff M, Timens W . Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?. Eur Respir Rev. 2017; 26(146). PMC: 9488745. DOI: 10.1183/16000617.0073-2017. View

17.

Bhadricha H, Patel V, Singh A, Savardekar L, Patil A, Surve S . Increased frequency of Th17 cells and IL-17 levels are associated with low bone mineral density in postmenopausal women. Sci Rep. 2021; 11(1):16155. PMC: 8352954. DOI: 10.1038/s41598-021-95640-0. View

18.

Hogg J, Timens W . The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol. 2008; 4:435-59. DOI: 10.1146/annurev.pathol.4.110807.092145. View

19.

Marandu T, Oduro J, Borkner L, Dekhtiarenko I, Uhrlaub J, Drabig A . Immune Protection against Virus Challenge in Aging Mice Is Not Affected by Latent Herpesviral Infections. J Virol. 2015; 89(22):11715-7. PMC: 4645637. DOI: 10.1128/JVI.01989-15. View

20.

Lee S, Yu Y, Trimpert J, Benthani F, Mairhofer M, Richter-Pechanska P . Virus-induced senescence is a driver and therapeutic target in COVID-19. Nature. 2021; 599(7884):283-289. DOI: 10.1038/s41586-021-03995-1. View