Birçok doku, normal fizyolojik olaylar veya yaralanmaya yanıt olarak çoğalma ve yenilenme yeteneğine sahiptir. Kök hücrelerin bu benzersiz nitelikleri, organizma yaşlandıkça doku homeostazisinde oluşan kayıplar, proliferatif ve dejeneratif hastalıklara neden olmaktadır. Organizma yaşlanmasıyla sadece kök hücreye özgü değişiklikler değil, aynı zamanda çeşitli dokularda kök hücre işlevini ve rejeneratif kapasiteyi de etkileyen yerel ve sistemik koşullarda da değişiklikler meydana gelmektedir. Erişkin kök hücreler, kendi kendini yenileme ve çoklu hücre tiplerine farklılaşma yeteneği ile karakterizedir. Her ne kadar ölümsüz olarak kabul edilseler de replikatif yaşlanmaya tabi olmadıkları için hasar birikimine duyarlılık göstermektedirler. Kök hücrelerde yaşa bağlı işlev bozukluğu, hem hücreye özgü hem de hücre dışı mekanizmalardan kaynaklanmaktadır. Sürekli olarak yenilenen dokularda, kök hücre ve organ düzeyinde yaşlanmayı ayırt edebilmek için kök hücrelerin yaşlanmasına etki eden faktörleri anlamak gerekmektedir. Kök hücre fonksiyonundaki gerileme, organizmanın sağlığı ve canlılığı üzerinde etkisi olan doku fizyolojisinde değişikliklere neden olur. Hücresel yaşlanmanın altında yatan mekanizmalar; telomer yıpranması, proteostazdaki değişiklikler, epigenetik ortamdaki kaymalar, DNA hasarı, mutasyon yükü ve mitokondriyal işlev bozukluğu gibi içsel değişiklikleri içermektedir. Ek olarak dışsal değişiklikler, yerel niş/ makroçevresel değişikliklerden sistemik seviye değişikliklerine, ışın tedavisi, patojen ve reaktif oksijene maruz kalma gibi daha yüksek seviyeli çevresel zararlara kadar değişebilir. Bu derlemede, kök hücre popülasyonlarının yaşlanmaları, yaşlanmalarına etki eden faktörler ve yaşlanmaya karşı kullanılan ajanlar ele alınmaktadır.
Anahtar Kelimeler: Kök hücreler; yaşlanma; terapötikler
Many tissues have an ability to proliferate and regenerate for response to normal physiological events or injury. These unique qualities of stem cells lead to proliferative and degenerative diseases that occur in tissue homeostasis as the organism ages. As the organism ages, changes occur not only in stem cell-specific changes, but also in local and systemic conditions that affect stem cell function and regenerative capacity in various tissues. Adult stem cells are characterized by the ability to self-renewal within a tissue and differentiate into multiple cell types. Although they are considered immortal, they are susceptible to damage accumulation, as they are not subject to replicative aging. Age-related dysfunction in stem cells is caused by both cell-specific and extracellular mechanisms. In order to understand stem cell aging and to understand organ-level aging, it is necessary to understand the factors that affect the aging of stem cells. Ultimately, declines in stem cell function result in changes in tissue physiology that have an impact on the health of the organism and its viability. Mechanisms that underlie cellular aging includes intrinsic alterations, such as telomere attrition, changes in proteostasis, shifts in the epigenetic landscape, DNA damage, mutational burden and mitochondrial dysfunction. Additionally, extrinsic alterations can range from local niche/macro environmental changes to systemic level alterations to higher level environmental insults, such as irradiation, pathogen, and reactive oxygen exposure. In this review, the aging of stem cell populations, the factors that cause their aging, and the agents used against aging are discussed.
Keywords: Stem cells; aging; therapeutics
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