Department of Biology, University of Maryland, College Park, MD, USA.
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Nat Commun. 2021 Mar 12;12(1):1615. doi: 10.1038/s41467-021-21900-2.
Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.
异常长寿的物种，包括许多蝙蝠，很少表现出明显的衰老迹象，这使得很难确定为什么不同物种的寿命存在差异。在这里，我们使用了 712 只已知年龄的蝙蝠的 DNA 甲基化 (DNAm) 图谱，代表 26 个物种，以鉴定与年龄和长寿相关的表观遗传变化。我们证明了 DNAm 可以准确预测生理年龄。在不同物种中，长寿与与年龄相关的位点的 DNAm 变化率呈负相关。此外，对几个蝙蝠基因组的分析表明，超甲基化的与年龄和长寿相关的位点不成比例地位于关键转录因子 (TF) 的启动子区域，并且富含与转录调控相关的组蛋白和染色质特征。预测的 TF 结合位点基序和富集分析表明，与年龄相关的甲基化变化受发育过程的影响，而与长寿相关的 DNAm 变化与先天免疫或肿瘤发生基因有关，这表明蝙蝠的长寿是由于增强的免疫反应和癌症抑制。
