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Biomarkers of senescence in non-human primate adipose depots relate to aging

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Abstract

Forty-three female African green monkeys (Chlorocebus aethiops sabaeus) were selected to represent young adult to advanced geriatric ages (7–24 years) to exhibit a wide range of obesity status (8–53% body fat) and diverse metabolic syndrome criteria such as diabetes, dyslipidemia, and hypertension. Subcutaneous and visceral adipose tissues were collected and evaluated for the presence of senescence cells in both whole tissue and single-cell isolates from subcutaneous sources, utilizing senescence-associated β-galactosidase (SAβ-gal) staining. Plasma samples were analyzed for selected metabolic and inflammatory biomarkers related to the senescence-associated secretory profile. Our results indicated that tissue staining scores did not differ between subcutaneous and intra-abdominal visceral depots and were highly related within individuals. Tissue staining was significantly associated with chronological age; however, no associations with fatness or metabolic syndrome criteria were observed. Associations with age were unchanged when obesity status was included in regression models. Isolated cell staining did positively relate to age but not tissue staining, suggesting some of the SAβ-gal-positive cells were stromal vascular cells or small adipocytes, but that mature large adipocytes, filtered out in the cell isolation process, are also likely to exhibit positive SAβ-gal staining. Plasminogen activator inhibitor-1 (PAI-1) concentration in circulation was the sole inflammation-related biomarker that positively associated with age and is considered to be a marker of senescent cell burden. Our study is the largest, most comprehensive assessment of adipose SAβ-gal staining in a relevant animal model of human aging, and confirms that this senescence-associated biomarker specifically indicates an age-related process.

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Acknowledgments

The authors wish to acknowledge the funding source listed below, all technicians involved in the care and evaluation of these animals, and the wonderful non-human primates that made this study possible.

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Funding

Funding for this project was provided by the National Institute Health grant number R01HL142930.

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Authors

Contributions

All authors participated in tissue sample collections, senescence scoring, and final manuscript review. KK is the Primary Investigator and the NIH grant recipient for this study, and performed all statistical evaluations. CS was the primary editor for the manuscript and created all figures and tables. AR and RV participated in ß-gal tissue staining. MB participated in histological evaluations. AO was the senior author of this manuscript, creating original drafts of each section, performed histological evaluations, and was the primary technician for ß-gal tissue staining, adipocyte isolation, and histological evaluations.

Corresponding author

Correspondence to Kylie Kavanagh.

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The authors declare that they have no conflict of interest.

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All animal procedures were conducted on a Wake Forest University Institutional Animal Care and Use Committee approved protocol according to recommendations in the Guide for Care and Use of Laboratory Animals and in compliance with the USDA Animal Welfare Act and Animal Welfare Regulations.

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Kavanagh, K., Sherrill, C., Ruggiero, A. et al. Biomarkers of senescence in non-human primate adipose depots relate to aging. GeroScience 43, 343–352 (2021). https://doi.org/10.1007/s11357-020-00230-z

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  • DOI: https://doi.org/10.1007/s11357-020-00230-z

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