Mitochondrial DNA sequences were found inserted in the nuclear genome of mouse peritoneal T lymphocytes that increased progressively with aging. These insertions were preferentially located at the pericentromeric heterochromatin. In the same individuals, binucleated T-cells with micronuclei showed a significantly increased frequency associated with age. Most of them were positive for centromere sequences, reflecting the loss of chromatids or whole chromosomes. The proliferative capacity of T lymphocytes decreased with age as well as the glutathione reductase activity, whereas the oxidized glutathione and malondialdehyde concentrations exhibited a significant increase.

These results may point to a common process that provides insights for a new approach to understanding immunosenescence. We propose a novel mechanism in which mitochondrial fragments, originated by the increased oxidative stress status during aging, accumulate inside the nuclear genome of T lymphocytes in a time-dependent way. The primary entrance of mitochondrial fragments at the pericentromeric regions may compromise chromosome segregation, causing genetic loss that leads to micronuclei formation, rendering aneuploid cells with reduced proliferation capacity, one of the hallmark of immunosenescence. Future experiments deciphering the mechanistic basis of this phenomenon are needed.

线粒体 DNA 序列被发现插入小鼠腹膜 T 淋巴细胞的核基因组中，随着年龄的增长逐渐增加。这些插入优先位于着丝粒周围的异染色质。在同一个体中，具有微核的双核 T 细胞显示出与年龄相关的显着增加的频率。它们中的大多数对着丝粒序列呈阳性，反映了染色单体或整个染色体的丢失。T淋巴细胞的增殖能力随着年龄的增长以及谷胱甘肽还原酶活性的降低而降低，而氧化型谷胱甘肽和丙二醛的浓度则显着增加。

这些结果可能指向一个共同的过程，为理解免疫衰老的新方法提供见解。我们提出了一种新机制，其中线粒体片段源于衰老过程中氧化应激状态的增加，以时间依赖性方式在 T 淋巴细胞的核基因组内积累。线粒体片段在着丝粒周围区域的主要入口可能会损害染色体分离，导致导致微核形成的遗传损失，使非整倍体细胞增殖能力降低，这是免疫衰老的标志之一。未来的实验需要破译这种现象的机制基础。