Klotho geni, yaşlanma ve DNA metilasyonu

Doğal bir süreç olan yaşlanma, zamanın akışı içerisinde canlı organizmada görülen anatomik ve fizyolojik değişiklikler olarak kendini gösterir. Yaşlanma sürecinde hem çevresel hem de genetik faktörler etkili olur. Genetik faktörler arasında farklı metabolik yolakları kontrol eden birçok gen yer alır. Bu derlemede ele alınan Klotho (kl) geni bunlardan sadece biridir. Kl geni ilk kez farelerde saptanmış ve bu genin işlev görememesi halinde erken yaşlanma belirtilerinin ortaya çıktığı ve farelerin kısa ömürlü olduğu görülmüştür. Yakın tarihli çalışmalar kl geni anlatımının DNA metilasyonu ile epigenik olarak kontrol edildiği yönünde sonuçlar ortaya koymaktadır. Henüz yayınlanmamış bir çalışmamızda da DNMT enzimlerinin insan kl geni anlatımı üzerinde baskılayıcı etkiye sahip olduğu saptanmıştır. İnsan kl geninin işleyiş mekanizmasının aydınlatılmasının, Kl proteininin anlatım düzeyine bağlı olarak ortaya çıkabilecek sağlık problemlerinin giderilmesinde daha güvenilir yöntemlerin izlenmesine olanak sağlayacağı kanısındayız.

Anahtar Kelimeler:

Klotho, yaşlanma, DNA metilasyonu, DNMT enzimleri

Klotho gene, aging and DNA methylation

Aging is a natural process, which shows itself as anatomical and physiological changes in living organisms in the course of time. There are both environmental and genetic factors affecting the aging process. Within the genetic factors, several genes controlling different metabolic pathways involve in the aging process. Klotho (kl) gene, that is the subject of this review, is just one of genetic factors. Kl gene was first identified in mice and it was shown that dysfunction of this gene causes premature aging symptoms and short-lived of the mice. Recently, it was reported that kl gene could be epigenetically controlled by DNA methylation. In our unpublished study, we showed that DNMT enzymes have down-regulatory effects on human kl gene expression. We believe that elucidating the regulation mechanism of the human kl gene allows us more reliable methods to be followed for eliminating health problems that may arise due to low expression of Kl protein.

Keywords:

Klotho, aging, DNA methylation, DNMT enzymes,

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