Identifying proteins causally related to COVID-19, healthspan and lifespan

“[…] we identified multiple proteins affecting COVID-19 and aging.”

BUFFALO, NY- April 24, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 16, Issue 7, entitled, “Using genetics and proteomics data to identify proteins causally related to COVID-19, healthspan and lifespan: a Mendelian randomization study.”

The COVID-19 pandemic poses a heavy burden on public health and accounts for substantial mortality and morbidity. Proteins are building blocks of life, but specific proteins causally related to COVID-19, healthspan and lifespan, have not been systematically examined. In this new study, researchers Jie V. Zhao, Minhao Yao, and Zhonghua Liu from The University of Hong Kong and Columbia University conducted a Mendelian randomization study to assess the effects of 1,361 plasma proteins on COVID-19, healthspan and lifespan, using large GWAS of severe COVID-19 (up to 13,769 cases and 1,072,442 controls), COVID-19 hospitalization (32,519 cases and 2,062,805 controls) and SARS-COV2 infection (122,616 cases and 2,475,240 controls), healthspan (n = 300,477) and parental lifespan (~0.8 million of European ancestry).

“We included both COVID-19 and healthspan and lifespan in the outcome, because COVID-19 which occurred in recent years reflects a new threat to longevity, whilst healthspan and lifespan reflect overall morbidity and mortality.”

The researchers identified 35, 43, and 63 proteins for severe COVID, COVID-19 hospitalization, and SARS-COV2 infection, and 4, 32, and 19 proteins for healthspan, father’s attained age, and mother’s attained age. In addition to some proteins reported previously, such as SFTPD related to severe COVID-19, the team identified novel proteins involved in inflammation and immunity (such as ICAM-2 and ICAM-5 which affect COVID-19 risk, CXCL9, HLA-DRA and LILRB4 for healthspan and lifespan), apoptosis (such as FGFR2 and ERBB4 which affect COVID-19 risk and FOXO3 which affect lifespan) and metabolism (such as PCSK9 which lowers lifespan). They found 2, 2, and 3 proteins shared between COVID-19 and healthspan/lifespan, such as CXADR and LEFTY2, shared between severe COVID-19 and healthspan/lifespan. Three proteins affecting COVID-19 and seven proteins affecting healthspan/lifespan are targeted by existing drugs.

“Our study provided novel insights into protein targets affecting COVID-19, healthspan and lifespan, with implications for developing new treatment and drug repurposing.”

Read the full paper: DOI: https://doi.org/10.18632/aging.205711 

Corresponding Authors: Jie V. Zhao, Zhonghua Liu

Corresponding Emails: janezhao@hku.hk, zl2509@cumc.columbia.edu 

Keywords: proteomics, healthspan, lifespan, COVID-19

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About Aging:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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