Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania,USA.
Research Institute, California Pacific Medical Center, University of California, San Francisco, San Francisco, California, USA.
J Gerontol A Biol Sci Med Sci. 2023 Oct 28;78(11):2039-2047. doi: 10.1093/gerona/glad019.
Studies using heterochronic parabiosis discovered that circulating factors mediate brain aging in animal models.
We assessed growth differentiation factors (GDF)-11 and GDF-8 using mass spectrometry and inhibitors follistatin and follistatin-like protein-3 (FSTL-3) with ELISA in the Cardiovascular Health Study (CHS; N = 1 506) and the Health, Aging and Body Composition (Health ABC) Study (N = 1 237). CLL-11 and beta-2 microglobulin (β2M) were measured with ELISA in a subset of 400 individuals in Health ABC. Associations were assessed with cognitive function, brain magnetic resonance imaging (MRI) findings (CHS only), and incident dementia using correlations, linear regression, and Cox proportional hazards models.
In CHS, levels of GDF-11, GDF-8, and follistatin were not correlated cross-sectionally with the 3MSE or DSST, brain MRI findings of white matter hyperintensity, atrophy, or small infarcts, nor were they associated with incident dementia. FSTL-3 was modestly correlated with poorer cognitive function, greater white matter hyperintensities, and atrophy on MRI, as well as with incident dementia with an adjusted hazard ratio (HR) of 1.72 (95% CI = 1.13, 2.61) per doubling of FSTL-3. FSTL-3 was not associated with cognition or dementia in Health ABC, but GDF-8 was associated with both. The adjusted HR for incident dementia was 1.50 (95% CI = 1.07, 2.10) per doubling of GDF-8.
Total GDF-11 level was not related to cognition or dementia in older adults. Associations of GDF-8 with cognitive outcomes in Health ABC were not expected, but consistent with animal models. Associations of FSTL-3 with cognition, brain abnormalities, and incident dementia in CHS implicate TGFβ superfamily inhibition in the pathogenesis of dementia.
使用异时共生的研究发现，循环因子介导动物模型中的大脑衰老。
我们使用质谱法评估了生长分化因子（GDF）-11 和 GDF-8，并使用 ELISA 评估了 CHS（N=1506）和健康、衰老和身体成分（Health ABC）研究（N=1237）中的卵泡抑素和卵泡抑素样蛋白-3（FSTL-3）。在 Health ABC 的一个 400 人的亚组中使用 ELISA 测量了 CLL-11 和β2-微球蛋白（β2M）。使用相关性、线性回归和 Cox 比例风险模型评估了认知功能、大脑磁共振成像（MRI）结果（仅 CHS）和痴呆的发生与这些因子的关联。
在 CHS 中，GDF-11、GDF-8 和卵泡抑素的水平与 3MSE 或 DSST、脑 MRI 白质高信号、萎缩或小梗塞的发现均无横断面相关性，也与痴呆的发生无关。FSTL-3 与认知功能较差、MRI 上白质高信号增加和萎缩以及 FSTL-3 加倍时发生痴呆的风险比（HR）为 1.72（95%CI=1.13，2.61）有适度相关性。FSTL-3 与 Health ABC 中的认知或痴呆无关，但 GDF-8 与两者均有关。GDF-8 每增加一倍，发生痴呆的调整后 HR 为 1.50（95%CI=1.07，2.10）。
在老年人中，总 GDF-11 水平与认知或痴呆无关。GDF-8 与 Health ABC 中认知结果的关联出乎意料，但与动物模型一致。FSTL-3 与 CHS 中的认知、脑异常和痴呆的发生有关，这表明 TGFβ 超家族抑制参与了痴呆的发病机制。
