Mosaic chromosomal alterations (mCAs) are frequently observed in cancer cells and are regarded as one of the common features of cancers. Strikingly, accumulating studies demonstrated that mCAs are also prevalent in elderly individuals without cancer, implying mCA could be a feature of aging and not necessarily a cancerous state. However, the genetic basis of mCA has been mostly unknown. Recent studies of autosomal mCA based on biobank-scale datasets, including UK Biobank and Biobank Japan, provided a glimpse into the underlying genetic mechanism. In this concise review, we briefly introduced mCA, its link with cancer and aging, and the emerging genetic mechanisms of this phenomenon. We highlighted the following aspects: (1) the interplay between somatic and inherited germline mutations in generating mosaicism; (2) monogenic and polygenic architectures of mCA; and (3) population-specific profiles of mCA. We provided a future perspective emphasizing the need to understand the connection between mCA and other characteristics of aging, in particular, the epigenetic and immunologic features.

镶嵌染色体改变 (mCA) 在癌细胞中经常观察到，被认为是癌症的常见特征之一。引人注目的是，越来越多的研究表明 mCA 在没有癌症的老年人中也很普遍，这意味着 mCA 可能是衰老的一个特征，不一定是癌症状态。然而，mCA 的遗传基础大多是未知的。最近基于生物库规模数据集（包括英国生物库和日本生物库）对常染色体 mCA 的研究提供了对潜在遗传机制的一瞥。在这篇简明的综述中，我们简要介绍了 mCA、它与癌症和衰老的联系，以及这种现象的新兴遗传机制。我们强调了以下几个方面：（1）体细胞和遗传性种系突变在产生嵌合体方面的相互作用；(2) mCA的单基因和多基因结构；(3) mCA 的特定人群概况。我们提供了一个未来的观点，强调需要了解 mCA 与衰老的其他特征之间的联系，特别是表观遗传和免疫学特征。