Kalyakulina Alena, Yusipov Igor, Kondakova Elena, Sivtseva Tatiana, Zakharova Raisa, Semenov Sergey, Klimova Tatiana, Ammosova Elena, Trukhanov Arseniy, Franceschi Claudio, Ivanchenko Mikhail
Artificial Intelligence Research Center, Institute of Information Technologies, Mathematics and Mechanics, Lobachevsky State University, 603022 Nizhny Novgorod, Russia.
Institute of Biogerontology, Lobachevsky State University, 603022 Nizhny Novgorod, Russia.
Int J Mol Sci. 2024 Dec 23;25(24):13741. doi: 10.3390/ijms252413741.
Yakutia is one of the coldest permanently inhabited regions in the world, characterized by a subarctic climate with average January temperatures near -40 °C and the minimum below -60 °C. Recently, we demonstrated accelerated epigenetic aging of the Yakutian population in comparison to their Central Russian counterparts, residing in a considerably milder climate. In this paper, we analyzed these cohorts from the inflammaging perspective and addressed two hypotheses: a mismatch in the immunological profiles and accelerated inflammatory aging in Yakuts. We found that the levels of 17 cytokines displayed statistically significant differences in the mean values between the groups (with minimal -value = 2.06 × 10), and 6 of them are among 10 SImAge markers. We demonstrated that five out of these six markers (PDGFB, CD40LG, VEGFA, PDGFA, and CXCL10) had higher mean levels in the Yakutian cohort, and therefore, due to their positive chronological age correlation, might indicate a trend toward accelerated inflammatory aging. At the same time, a statistically significant biological age acceleration difference between the two cohorts according to the inflammatory SImAge clock was not detected because they had similar levels of CXCL9, CCL22, and IL6, the top contributing biomarkers to SImAge. We introduced an explainable deep neural network to separate individual inflammatory profiles between the two groups, resulting in over 95% accuracy. The obtained results allow for hypothesizing the specificity of cytokine and chemokine profiles among people living in extremely cold climates, possibly reflecting the effects of long-term human (dis)adaptation to cold conditions related to inflammaging and the risk of developing a number of pathologies.
雅库特是世界上最寒冷的有人长期居住的地区之一，其特点是亚北极气候，1月份平均气温接近-40°C，最低气温低于-60°C。最近，我们证明了与居住在气候温和得多的俄罗斯中部地区的同龄人相比，雅库特人群的表观遗传衰老加速。在本文中，我们从炎症衰老的角度分析了这些队列，并探讨了两个假设：雅库特人的免疫特征不匹配和炎症衰老加速。我们发现，17种细胞因子的水平在两组之间的平均值上显示出统计学上的显著差异（最小值 = 2.06×10），其中6种是10种SImAge标志物中的一部分。我们证明，这6种标志物中的5种（PDGFB、CD40LG、VEGFA、PDGFA和CXCL10）在雅库特队列中的平均水平较高，因此，由于它们与实际年龄呈正相关，可能表明存在炎症衰老加速的趋势。同时，根据炎症SImAge时钟，未检测到两组之间在生物学年龄加速方面存在统计学上的显著差异，因为它们的CXCL9、CCL22和IL6水平相似，而这三种是对SImAge贡献最大的生物标志物。我们引入了一个可解释的深度神经网络来区分两组之间的个体炎症特征，准确率超过95%。所得结果使我们能够推测生活在极端寒冷气候中的人群中细胞因子和趋化因子谱的特异性，这可能反映了长期人类（不）适应寒冷条件与炎症衰老以及多种疾病发生风险之间的关系。
