Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
College of Health and Medicine, University of Tasmania, Hobart, Australia.
Geroscience. 2021 Feb;43(1):343-352. doi: 10.1007/s11357-020-00230-z. Epub 2020 Jul 23.
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.
选择了 43 只雌性非洲绿猴（Chlorocebus aethiops sabaeus），代表年轻到老年（7-24 岁），以表现出广泛的肥胖状态（8-53%的体脂）和多种代谢综合征标准，如糖尿病、血脂异常和高血压。收集了皮下和内脏脂肪组织，并利用衰老相关的β-半乳糖苷酶（SAβ-gal）染色，对全组织和来自皮下源的单细胞分离物中的衰老细胞进行评估。分析了与衰老相关分泌表型相关的选定代谢和炎症生物标志物的血浆样本。我们的结果表明，皮下和腹腔内脏脂肪组织中的组织染色评分没有差异，并且在个体内高度相关。组织染色与实际年龄显著相关；然而，与肥胖或代谢综合征标准没有关联。当肥胖状态被包含在回归模型中时，与年龄的关联保持不变。分离细胞的染色与年龄呈正相关，但与组织染色无关，这表明一些 SAβ-gal 阳性细胞是基质血管细胞或小脂肪细胞，但在细胞分离过程中过滤出的成熟大脂肪细胞也可能表现出阳性 SAβ-gal 染色。循环中纤溶酶原激活物抑制剂-1（PAI-1）浓度是唯一与年龄呈正相关的炎症相关生物标志物，被认为是衰老细胞负担的标志物。我们的研究是在人类衰老的相关动物模型中对脂肪组织 SAβ-gal 染色的最大、最全面的评估，证实了这种衰老相关的生物标志物特别表明了与年龄相关的过程。
