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.