Senolytics reduce coronavirus-related mortality in old mice-Reference-Cited by-同舟云学术

Senolytics reduce coronavirus-related mortality in old mice

Published:2021-07-16 Issue:6552 Volume:373 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Camell Christina D.¹^ORCID,Yousefzadeh Matthew J.¹^ORCID,Zhu Yi²³^ORCID,Prata Larissa G. P. Langhi²^ORCID,Huggins Matthew A.⁴^ORCID,Pierson Mark⁴,Zhang Lei¹,O’Kelly Ryan D.¹,Pirtskhalava Tamar²,Xun Pengcheng⁵^ORCID,Ejima Keisuke⁵^ORCID,Xue Ailing²,Tripathi Utkarsh²^ORCID,Espindola-Netto Jair Machado²,Giorgadze Nino²,Atkinson Elizabeth J.²⁶^ORCID,Inman Christina L.²,Johnson Kurt O.²^ORCID,Cholensky Stephanie H.¹,Carlson Timothy W.⁷⁸^ORCID,LeBrasseur Nathan K.²⁹^ORCID,Khosla Sundeep²¹⁰^ORCID,O’Sullivan M. Gerard⁷⁸^ORCID,Allison David B.⁵^ORCID,Jameson Stephen C.⁴^ORCID,Meves Alexander¹¹^ORCID,Li Ming¹¹,Prakash Y. S.³¹²^ORCID,Chiarella Sergio E.¹³^ORCID,Hamilton Sara E.⁴^ORCID,Tchkonia Tamara²³^ORCID,Niedernhofer Laura J.¹^ORCID,Kirkland James L.²³¹⁴^ORCID,Robbins Paul D.¹^ORCID

Affiliation:

1. Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.

2. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.

3. Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.

4. Department of Laboratory Medicine and Pathology and Center of Immunology, University of Minnesota, Minneapolis, MN, USA.

5. Department of Epidemiology and Biostatistics, School of Public Health, Indiana University–Bloomington, Bloomington, IN, USA.

6. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

7. Masonic Cancer Center Comparative Pathology Shared Resource, University of Minnesota, St. Paul, MN, USA.

8. Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN, USA.

9. Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA.

10. Division of Endocrinology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.

11. Department of Dermatology, Mayo Clinic, Rochester, MN, USA.

12. Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.

13. Division of Allergic Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA.

14. Division of General Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.

Abstract

Senescent cells exacerbate COVID-19 Cellular senescence is a state elicited in response to stress signals and is associated with a damaging secretory phenotype. The number of senescent cells increases with advanced age and this in turn drives age-related diseases. Camell et al. show that senescent cells have an amplified inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (see the Perspective by Cox and Lord). This response is communicated to nonsenescent cells, suppressing viral defense mechanisms and increasing the expression of viral entry proteins. In old mice infected with a SARS-CoV-2–related virus, treatment with senolytics to reduce the senolytic cell burden reduced mortality and increased antiviral antibodies. Science , abe4832, this issue p. eabe4832 ; see also abi4474, p. 281

Funder

National Institute on Aging

University of Minnesota Clinical and Translational Science Institute

Connor Fund

Robert J. and Theresa W. Ryan Fund

Noaber Foundation

Glenn Foundation for Medical Research

American Federation for Aging Research

American Foundation for Aging Research

Publisher

American Association for the Advancement of Science (AAAS)

Subject