Effect of Energy Restriction on Lifespan via Sirtuins: SIRT1 and SIRT3

Abstract

Sirtuin protein family, the homologue of the yeast Sir2 protein in the mammalian organism, consists of 7 members (SIRT1-7). Sirtuin-1 (SIRT1), which has the highest Sir2 similarity, draws attention due to the positive effects of its activation on metabolism. The different localizations of sirtuins in the cell cause diversity in their functions, providing a wide range of effects from energy homeostasis to DNA repair mechanisms. The first discovered regulator of sirtuins was cellular NAD molecule. As a result of the organism’s exposure to less energy intake than normal, this restriction causes the NAD+/ NADH ratio in the cell to change in favor of NAD+. This new balance has been found to be associated with prolonged lifespan as a result of increased sirtuin activation in organisms at all levels, from yeasts to mammals. After the deacetylation functions were discovered, sirtuins were also referred to as ‘NAD-dependent deacetylase’. Despite being often limited to deacetylate lysine residues of histone proteins in lower organisms, sirtuins have a wide variety of protein targets in the mammalian organism. The purpose of this review article is to provide an overview of the importance of sirtuin proteins that can be induced by dietary changes and to summarize the effects of SIRT1 and SIRT3, which stand out with their positive metabolic functions, on metabolism through some target substrates.

Keywords

• Sirtuin
• energy
• SIRT1
• deacetylation
• epigenetic

Kalori Kısıtlamasının Sirtüinler Aracılığı ile Yaşam Süresine Etkisi: SIRT1 ve SIRT3

Abstract

Maya Sir2 proteininin memeli organizmadaki homoloğu olan sirtüin protein ailesi 7 üyeden oluşmaktadır (SIRT1-7). Sir2 benzerliği en yüksek olan Sirtüin-1 (SIRT1), aktivasyonunun metabolizmaya sağladığı pozitif etkiler nedeniyle dikkat çekmektedir. Sirtüinlerin hücredeki farklı lokalizasyonları, işlevlerinde de çeşitliliğe neden olarak enerji homeostazından DNA onarım mekanizmalarına kadar geniş bir etki alanı sağlamaktadır. Sirtüinlerin keşfedilen ilk regülatörü hücresel nikotinamid adenin dinükleotid (NAD) molekülü olmuştur. Organizmanın normalden az enerji alımına maruz kalması sonucu, oluşan bu kısıtlılık hücrede NAD+/NADH oranının NAD+ lehine değişmesine neden olmaktadır. Oluşan bu yeni denge, mayalardan memelilere her düzeydeki organizmada artmış sirtüin aktivasyonu sonucu uzamış yaşam süresi ile ilişkili bulunmuştur. Deasetilasyon işlevleri keşfedildikten sonra, sirtüinler ‘NAD-bağımlı deasetilaz’lar olarak da anılmaya başlamıştır. Düşük organizmalarda çoğunlukla histon proteinlerinin lizin rezidülerini deasetile etmekle sınırlı olsalar da, sirtünlerin memeli organizmasında çok çeşitli protein hedefleri mevcuttur. Bu derleme makalenin amacı, diyete bağlı değişiklikler ile indüklenebilen sirtüin proteinlerinin önemine dair genel bir bakış açısı sağlamak ve pozitif metabolik işlevleri ile öne çıkan SIRT1 ve SIRT3’ün bazı hedef substratları aracılığıyla metabolizma üzerindeki etkilerini özetlemektir.

Keywords

• Sirtüin
• enerji
• SIRT1
• deasetilasyon
• epigenetik

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