The biological markers of aging used to predict physical health status in older people are of great interest. Telomere shortening, which occurs during the process of cell replication, was initially considered a promising biomarker for the prediction of age and age-related outcomes (e.g., diseases, longevity). However, the high instability in detection and low correlation with age-related outcomes limit the extension of telomere length to the field of prediction. Currently, a growing number of studies have shown that dynamic DNA methylation throughout human lifetime exhibits strong correlation with age and age-related outcomes. Indeed, many researchers have built age prediction models with high accuracy based on age-dependent methylation changes in certain CpG loci. For now, DNA methylation based on epigenetic clocks, namely epigenetic or DNA methylation age, serves as a new standard to track chronological age and predict biological age. Measures of age acceleration (Δage, DNA methylation age – chronological age) have been developed to assess the health status of a person. In addition, there is evidence that an accelerated epigenetic age exists in patients with certain age-related diseases (e.g., Alzheimer’s disease, cardiovascular disease). In this review, we provide an overview of the dynamic signatures of DNA methylation during aging and emphasize its practical utility in the prediction of various age-related outcomes.

Colon cancer (CC) is one of the major malignancies worldwide, whose pathogenesis is complex and requires the accumulated alteration of multiple genes and signaling pathways. Condensins are multi-protein complexes that play pivotal roles in chromosome assembly and segregation during mitosis, meiosis and even tumorigenesis. Using tissue microarrays by immunohistochemistry and hematoxylin–eosin staining, we found that non-SMC condensin I complex subunit H (NCAPH) in colon cancerous tissues was higher than that in all corresponding adjacent non-cancerous tissues. We then characterized the exact function of the NCAPH in CC. We provided evidences showing that NCAPH is highly expressed in colorectal cancer cell lines comparing with normal human colonic epithelial cells, and identified many NCAPH mutations in CC patients. We found that depletion of NCAPH inhibits CC cell proliferation, migration in vitro and xenograft tumor formation in vivo. Furthermore, NCAPH knockdown promotes cell apoptosis and cell cycle arrest at G2/M phase. Interestingly, the NCAPH high expression in tumor tissues of colon patients had a significantly better prognosis and survival rate than low-expression patients, suggesting that NCAPH high expression promotes colonic cancerous cell proliferation; on the other hand, it may also sensitize these cells responding to chemo- or radio-therapies. Collectively, these findings reveal an important role of NCAPH in CC, indicating that NCAPH could be used as a new therapeutic target in future.

The permanent human settlement of the Tibetan Plateau (TP) has been suggested to have been facilitated by the introduction of barley agriculture ∼3.6 kilo-years ago (ka). However, how barley agriculture spread onto the TP remains unknown. Given that the lower altitudes in the northeastern TP were occupied by millet cultivators from 5.2 ka, who also adopted barley farming ∼4 ka, it is highly possible that it was millet farmers who brought barley agriculture onto the TP ∼3.6 ka. To test this hypothesis, we analyzed mitochondrial DNA (mtDNA) from 8277 Tibetans and 58 514 individuals from surrounding populations, including 682 newly sequenced whole mitogenomes. Multiple lines of evidence, together with radiocarbon dating of cereal remains at different elevations, supports the scenario that two haplogroups (M9a1a1c1b1a and A11a1a), which are common in contemporary Tibetans (20.9%) and were probably even more common (40–50%) in early Tibetans prior to historical immigrations to the TP, represent the genetic legacy of the Neolithic millet farmers. Both haplogroups originated in northern China between 10.0–6.0 ka and differentiated in the ancestors of modern Tibetans ∼5.2–4.0 ka, matching the dispersal history of millet farming. By showing that substantial genetic components in contemporary Tibetans can trace their ancestry back to the Neolithic millet farmers, our study reveals that millet farmers adopted and brought barley agriculture to the TP ∼3.6–3.3 ka, and made an important contribution to the Tibetan gene pool.