İnsan Telomerleri 1000 Nükleotit Arttırılarak Yaşlanma Süresi Uzatıldı

İnsan Telomerleri

Gençlerde uzunluk bakımından 8-10 bin nükleotit arası olarak bilinen telomerler her hücre bölünmes safhasında bir miktar kısalarak en sonunda hücrenin bölününemeyerek ölmesine yol açmaktadır.Stanford Tıp Fakültesi’nden bilim insanlarının keşfettiği yeni bir metot ile insan telomerlerini 1000 nükleotit daha uzatarak yaşlanmayı geçiktirmeyi başardılar.



 Stanford Tıp Fakültesi’nde bilim insanları tarafından düzenlenen yeni bir metot ile kromozomların sonlarındaki koruyucu modül görevini yapan telomerlerin uzunluğu arttırılması ile hastalıkların ve yaşlanmanın hızı azaltılabilir.


Tedavisi gerçekleştirilen hücreler  tedavi edilmeyen hücrelere göre daha genç halde kalabiliyor. Modifiye RNA kullanılarak yapılan prosedürde araştırma veya ilaç denemeleri için fazla sayıda hücre ye erişilip üretimi gerçekleştirildi. Prosedür yardımıyla deri hücrelerindeki telomerler tedavisi mümkün olmayan hücrelere göre 40 keze kadar uzatılabildi.

Telomerler DNA zincirlerinin sonunda koruyucu görev gören kapaklar gibi çalışıyor. Gençlerde telomer uzunluğu 8,000-10,000 nükleotite kadar olabiliyor. Her hücre bölünmesinde bunlar kısalıyor, ve kritik uzunluğa ulaştığında hücre bölünmesi duruyor ve hücreler ölmeye başlıyor. Hücrelerin iç saati nedeniyle laboratuvar ortamında hücrelerin canlı tutulması oldukça zor. Ancak birkaç hücre bölünmesi gerçekleşebiliyordu. Hücre İçi Saati Geriye Kurmak   “Artık insan telomerlerinin 1000 nükleotite kadar uzatmanın yolunu bulduk hücre saatleri bu şekilde geriye almak insan ömründe pek çok yıla denk geliyor.


Bu sayede ilaç testleri veya hastalık modelleme çalışmaları için hücre sayısı büyük  ölçüde artıyor,” diyor Stanford’dan mikrobiyoloji ve immünoloji Prof. Dr. Helen Blau . Araştırmacılar modifiye mesajcı RNA kullanarak telomerleri uzattılar. DNA’daki genlerden aldığı bilgileri hücrelerin protein fabrikalarına taşıyan RNA’lar bu deneyde önemli rol taşıyor.


Deneydeki RNA’larda kodlama sekansı için TERT adı verilen doğal olarak telomeraz enzimi içeren aktif bir içerik kullanılıyor. Kök  hücreler tarafından tanımlanan telomeraz enzimi sperm ve yumurta hücrelerini meydana getirerek bu hücrelerin tam şeklinin bir sonraki nesle aktarılmasını güvence altına alıyor. Buna istinaden, diğer hücre türlerinde çok az düzeyde telomeraz enzimi tanımlanıyor.

Geçici Etkinin Avantajı Yeni geliştirilen tekniği bir diğer önemli avantajı ise diğer potansiyel metotlara göre geçici olması . Modifiye RNA hücrenin tedaviye bağışıklık cevabını azaltmak için tasarlanıyor ve TERT şifrelenen mesaj modifiye olmayan mesajda biraz daha uzun tutunuyor. Fakat 48 saat sonunda harcanarak yok oluyor. Sonrasında ise uzayan telomerler sonrasında progresif bir şekilde hücre bölünmesi ile tekrar kısalıyor. Biyolojik açıdan tedavi edilen hücreler böylece sonsuza kadar bölünmüyor, bu zaten insanlarda kanser riski taşıyacağından çok tehlikeli. Araştırmacılar modifiye mRNA’nın birkaç muhtemel uygulamasını buldular. 1000 nükleotit eklemek insan telomerlerinin % 10 daha fazla artışını gösteriyor.


Petri kabında bölünen cilt hücrelerinin 28, kas hücrelerinin ise 3 kez daha fazla bölündüğü anlaşıldı. “Modifiye TERT mRNA’nın çalıştığını görünce gerçekten şaşırdık ve memnun olduk. Çünkü TERT çok düzenleyici olduğundan diğer bir telomeraz bileşiğine bağlanmakta zorundadı. Daha önceki mRNA kodlanmış TERT denemeleri telomeraza karşı bir bağışıklık geliştirerek kaldırıcı bir etki yarattı. Buna karşın yeni metot nonimmünojenik.


Mevcut geçici telomer uzatıcı etkiler oldukça yavaş çalışıyor ,fakat bizim metotumuz sadece birkaç gün içinde telomer kısalmasını geriye çevirererek, nerdeyse on yıllık normal bir yaşlanma getiriyor. Bu da yeni tedavimizin kısa ve sürekli olmayacağını gösteriyor,” diyor Ramunas.
telomer ile ilgili görsel sonucu

Tedavinin Potansiyel Kullanım Alanları “Yeni yaklaşımımız yaşlanmaya ilişkin hastalıkları tedavi etmenin veya önlemenin yolunu açıyor. Telomer kısalmasıyla ilişkili elden ayaktan düşüren genetik hastalıklar için potansiyel bir tedavi olabilir,” diyor Blaus.


Blau ve meslektaşları daha önce,Duchenne müsküler distropisi adı verilen erkek çocuklarında kas kök hücrelerinin telomer uzunluğunun daha kısa olduğunu göstermişti. İşte bu bulgunun sadece hücrelerin fonksiyonunu anlamaya değil yeni kaslar üretmede neden fonksiyonel olmadığını ve laboratuar çalışmalarında neden etkilenen hücrelerin kısıtlı bir kabiliyeti olduğunu gösteriyor.


Çalışmayı sürdürren bilim insanları  şimdi diğer hücre tiplerinde yeni tekniği test ediyorlar. Tedavinin yaşlanmaya ilişkin genetik hastalıklar, kalp ve diyabet gibi hastalıklar üzerine potansiyel tedavi yöntemleri üretebileceği tahmin edilebilmekte ve “Bu çalışma telomer uzamasının geliştirilmesin ilişkin birinci adımı temsil ederken, hücre terapilerini geliştirerek, muhtemel hızlanmış yaşlanma bozukluklarını tedavi etmeyi amaçlıyor,” diyor.Stanford’da önceden Kardivasküler Tıp Uzmanı Prof. Dr. John Cooke Bugün Houston Methodist Araştırma Enstitüsü’nde kardivasküler bilimlere başkanlığını sürdürüyor.


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