不同年龄供者胰岛中衰老相关基因和胰腺功能相关基因表达状态及相关性分析。
Analysis of Expression Status and Relationship Between Senescence-related Genes and Pancreatic Function-related Genes in Human Islets of Langerhans from Donors of Various Ages.
机构信息
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
出版信息
In Vivo. 2024 Sep-Oct;38(5):2165-2171. doi: 10.21873/invivo.13679.
BACKGROUND/AIM: Although studies on senescence-related genes using human islets of Langerhans have been performed, the expression of senescence-related genes and their association with functional genes in islets remain insufficiently investigated. We aimed to determine whether and what types of senescent-related genes are expressed in islets and identify their correlations with pancreatic function-related genes by using islets isolated for transplantation from individuals of various ages.
MATERIALS AND METHODS
Islets from deceased donors of both sexes and different ages were used for analysis. The expression status of senescence-related genes (glutaminase 1, interleukin 6, interleukin 8, cyclin-dependent kinase inhibitor 2A, cyclin-dependent kinase inhibitor 1A, and senescence-associated beta-galactosidase) and pancreatic function-related genes (glucagon and insulin) was examined by reverse transcription-quantitative polymerase chain reaction, and their relationships with age were investigated.
RESULTS
We obtained isolated human islets from 18 deceased multiorgan donors. There was no correlation between donor age and expression of any of the senescence-related genes. Regarding correlations between donor age and pancreatic function-related genes, age was positively correlated only with INS (r=0.49, p=0.03). INS expression was not correlated with that of GLS1 (r=0.23, p=0.34), IL6 (r=-0.06, p=0.79), or IL8 (r=-0.1, p=0.12), but positively related with p16 (r=0.89, p<0.0001), p21 (r=0.51, p=0.02), and SA-β-gal (r=0.52, p=0.02).
CONCLUSION
We showed the functional potential even of aged islets, which were originally thought to be functionally impaired. We were unable to identify any senescence-related genes expressed in islets from donors of different ages. Therefore, a new index is needed to evaluate not only actual chronological age but also organ- and cell-specific age.
背景/目的：尽管已经对人胰岛中的衰老相关基因进行了研究，但胰岛中衰老相关基因的表达及其与胰岛功能相关基因的相关性仍未得到充分研究。我们旨在通过使用来自不同年龄个体的胰岛分离物，确定胰岛中是否表达以及表达何种类型的衰老相关基因，并鉴定其与胰腺功能相关基因的相关性。
材料和方法
使用来自不同性别和不同年龄的已故供体的胰岛进行分析。通过逆转录定量聚合酶链反应检测衰老相关基因（谷氨酰胺酶 1、白细胞介素 6、白细胞介素 8、细胞周期蛋白依赖性激酶抑制剂 2A、细胞周期蛋白依赖性激酶抑制剂 1A 和衰老相关β-半乳糖苷酶）和胰腺功能相关基因（胰高血糖素和胰岛素）的表达状态，并研究其与年龄的关系。
结果
我们从 18 名已故多器官供体中获得了分离的人胰岛。供体年龄与任何衰老相关基因的表达均无相关性。关于供体年龄与胰腺功能相关基因之间的相关性，年龄仅与 INS 呈正相关（r=0.49，p=0.03）。INS 表达与 GLS1（r=0.23，p=0.34）、IL6（r=-0.06，p=0.79）或 IL8（r=-0.1，p=0.12）不相关，但与 p16（r=0.89，p<0.0001）、p21（r=0.51，p=0.02）和 SA-β-gal（r=0.52，p=0.02）呈正相关。
结论
我们展示了即使是原本被认为功能受损的老年胰岛也具有功能潜力。我们无法鉴定出来自不同年龄供体的胰岛中表达的任何衰老相关基因。因此，需要一种新的指标来评估不仅是实际的年龄，还有器官和细胞特异性的年龄。
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