In a recent seminar trip to University of Michigan, I met with Bruce Richardson who explained the very interesting etiology of lupus, an autoimmune disease. He told me that lupus is caused by DNA demethylation, and substances that decrease DNA methylation could cause lupus as a side effect. Cancer drugs such as 5-aza with demethylation effect certainly have similar side effect, but cancer patients usually have bigger worries than DNA demethylation and lupus. He also explained why females are more likely to develop lupus, because an important autoimmune gene is on the X-chr. Females should have one X-chr silenced except in lupus patients, whereas males only have one copy of the gene to express.
Because of Bing Ren‘s talk on the association of aging with increased H3K27me3, I had always assumed that DNA methylation increases with aging. However, Bruce told me that in general DNA methylation decrease with aging, which could agree with Michael Zhang‘s idea that transposable elements are more active with aging. So perhaps the increased H3K27me3 with aging reflects the way cells compensate for the loss of DNA methylation. Since DNA methylation and H3K27me3 have their respective genome-wide specificities, maybe the specificity difference between the two could help explain the common aging-related disease.
Bruce also mentioned that antioxidant can reinforce DNA methylation, which partly explains why it is an anti-aging and anti-lupus agent. Also, from David Moore‘s research before, having a methylation-rich diet (plenty from vitamin tablet) could also prevent DNA demethylation, and perhaps aging as well.