Our study investigates gene expression in adipose tissue of Ames dwarf (df/df) mice, whose deficiency in growth hormone is linked to health and extended lifespan. Recognizing adipose tissue influence on metabolism, aging, and related diseases, we aim to understand its contribution to the health and longevity of df/df mice. We have identified gene and transcript expression patterns associated with critical biological functions, including metabolism, stress response, and resistance to cancer. Intriguingly, we identified genes that, despite maintaining unchanged expression levels, switch between different isoforms, impacting essential cellular functions such as tumor suppression, oncogenic activity, ATP transport, and lipid biosynthesis and storage. The isoform switching is associated with changes in protein domains, retention of introns, initiation of nonsense-mediated decay, and emergence of intrinsically disordered regions. Moreover, we detected various alternative splicing events that may drive these structural alterations. We also found changes in the expression of long non-coding RNAs (lncRNAs) that may be involved in the aging process and disease resistance by regulating crucial genes in survival and metabolism. Through weighted gene co-expression network analysis, we have linked four lncRNAs with 29 genes, which contribute to protein complexes such as the Mili-Tdrd1-Tdrd12 complex. Beyond safeguarding DNA integrity, this complex also has a wider impact on gene regulation, chromatin structure, and metabolic control. Our detailed investigation provides insight into the molecular foundations of the remarkable health and longevity of df/df mice, emphasizing the significance of adipose tissue in aging and identifying new avenues for health-promoting therapeutic strategies.

我们的研究调查了 Ames 矮小 （df/df） 小鼠脂肪组织中的基因表达，其生长激素缺乏与健康和延长寿命有关。认识到脂肪组织对新陈代谢、衰老和相关疾病的影响，我们的目标是了解它对 df/df 小鼠健康和长寿的贡献。我们已经确定了与关键生物学功能相关的基因和转录本表达模式，包括新陈代谢、应激反应和对癌症的抵抗力。有趣的是，我们鉴定了尽管保持表达水平不变，但在不同亚型之间切换的基因，影响基本的细胞功能，如肿瘤抑制、致癌活性、ATP 转运以及脂质生物合成和储存。亚型转换与蛋白质结构域的变化、内含子的保留、无义介导的衰变的开始以及固有无序区域的出现有关。此外，我们检测到可能驱动这些结构改变的各种选择性剪接事件。我们还发现，通过调节生存和代谢中的关键基因，可能参与衰老过程和抗病性的长链非编码 RNA （lncRNAs） 的表达发生变化。通过加权基因共表达网络分析，我们已经将 4 个 lncRNAs 与 29 个基因连接起来，这些基因有助于蛋白质复合物，例如 Mili-Tdrd1-Tdrd12 复合物。除了保护 DNA 完整性外，该复合物还对基因调控、染色质结构和代谢控制产生更广泛的影响。 我们的详细研究深入了解了 df/df 小鼠显着健康和长寿的分子基础，强调了脂肪组织在衰老中的重要性，并确定了促进健康的治疗策略的新途径。