Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA 94107, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94107, USA.
Aging (Albany NY). 2023 Aug 14;15(15):7381-7396. doi: 10.18632/aging.204961.
Aging biomarkers may be related to each other through direct co-regulation and/or through being regulated by common processes associated with chronological aging or stress. Klotho is an aging regulator that acts as a circulating hormone with critical involvement in regulating insulin signaling, phosphate homeostasis, oxidative stress, and age-related inflammatory functioning. Both klotho and telomere length are biomarkers of biological aging and decrease with age; however, the relationship between them is not well understood. Here we test the association between klotho levels and the telomere length of specific sorted immune cells among a healthy sample of mothers caregiving for a child with autism spectrum disorder (ASD; i.e., experiencing higher caregiving stress) or a child without ASD, covarying age and body mass index, in order to understand if high stress associated with caregiving for a child with an ASD may be involved in any association between these aging biomarkers. In 178 caregiving women ( = 90 high-stress mothers of children with ASD, = 88 low-stress mothers of neurotypical children), we found that klotho levels were positively associated with telomere length in PBMCs (an effect driven by CD4+ and CD8+CD28- T cells) among high-stress mothers of children with an ASD but not among low-stress mothers of neurotypical children. There were no significant associations between klotho and telomerase activity in either group, across cell types assessed here. Our results suggest that klotho levels and telomere length may be associated through a coordinated downregulation of longevity factors occurring under higher stress caregiving conditions.
衰老生物标志物可能通过直接的共同调控，或者通过受与生理衰老或应激相关的共同过程的调控而相互关联。Klotho 是一种衰老调节因子，作为一种循环激素发挥作用，在调节胰岛素信号、磷酸盐稳态、氧化应激和与年龄相关的炎症功能方面具有关键作用。Klotho 和端粒长度都是生物衰老的生物标志物，随年龄增长而减少；然而，它们之间的关系尚不清楚。在这里，我们在一个由照顾自闭症谱系障碍（ASD）儿童（即经历更高的照顾压力）或没有 ASD 的儿童的母亲组成的健康样本中，测试了 Klotho 水平与特定免疫细胞端粒长度之间的关系，这些免疫细胞经过了分类，共变量为年龄和体重指数，以了解与照顾 ASD 儿童相关的高压力是否可能参与这些衰老生物标志物之间的任何关联。在 178 名照顾女性中（= 90 名有 ASD 儿童的高压力母亲，= 88 名有神经典型儿童的低压力母亲），我们发现，在有 ASD 儿童的高压力母亲中，Klotho 水平与 PBMCs 中的端粒长度呈正相关（这种效应是由 CD4+和 CD8+CD28- T 细胞驱动的），但在有神经典型儿童的低压力母亲中则没有。在这两组中，跨评估的细胞类型，Klotho 与端粒酶活性之间均无显著关联。我们的结果表明，Klotho 水平和端粒长度可能通过在更高压力的照顾条件下发生的长寿因子的协调下调而相关联。
