Wang Ming, Yan Yan, Zhang Zhengguo, Yao Xiaohan, Duan Xixi, Jiang Ziming, An Junfeng, Zheng Peiguo, Han Yijie, Wu Hao, Wang Zhaoqing, Glauben Rainer, Qin Zhihai
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China.
Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
iScience. 2021 Jun 24;24(7):102766. doi: 10.1016/j.isci.2021.102766. eCollection 2021 Jul 23.
Inflammaging is associated with an increased risk of chronic disease. Monocytes are the principal immune cells for the production of inflammatory cytokines and contribute to inflammaging in the elderly. However, the underlying mechanisms remain largely unknown. Here, we found that monocytes from aged individuals contained high levels of lipid droplets (LDs), and this increase was correlated with impaired fatty acid oxidation. Downregulated peroxisome proliferator-activated receptor (PPAR)-α may be responsible for the pro-inflammatory phenotype of monocytes in aged individuals, as it was positively correlated with LD accumulation and increasing TNF-α concentration. Interestingly, interventions that result in PPAR-α upregulation, such as fenofibrate treatment, TNF-α neutralization, or calorie restriction, reversed the effect of aging on monocytes. Thus the downregulation of PPAR-α and LD levels in monocytes represents a novel biomarker for inflammaging. Furthermore, PPAR-α activation in the elderly may also alleviate long-term inflammaging, preventing the development of life-limiting chronic diseases.
炎症衰老与慢性疾病风险增加相关。单核细胞是产生炎性细胞因子的主要免疫细胞，且在老年人的炎症衰老过程中起作用。然而，其潜在机制仍 largely 未知。在此，我们发现老年个体的单核细胞含有高水平的脂滴（LDs），且这种增加与脂肪酸氧化受损相关。过氧化物酶体增殖物激活受体（PPAR）-α 的下调可能是老年个体单核细胞促炎表型的原因，因为它与 LD 积累及肿瘤坏死因子-α（TNF-α）浓度升高呈正相关。有趣的是，导致 PPAR-α 上调的干预措施，如非诺贝特治疗、TNF-α 中和或热量限制，可逆转衰老对单核细胞的影响。因此，单核细胞中 PPAR-α 和 LD 水平的下调代表了炎症衰老的一种新生物标志物。此外，老年人中 PPAR-α 的激活也可能减轻长期炎症衰老，预防危及生命的慢性疾病的发展。
