Mariño Guillermo, López-Otín Carlos
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
Autophagy. 2008 Aug;4(6):807-9. doi: 10.4161/auto.6478. Epub 2008 Jun 20.
It is widely-assumed that the autophagic activity of living cells decreases with age and probably contributes to the accumulation of damaged macromolecules and organelles during aging. Over the last few years, the study of segmental progeroid syndromes in which certain aspects of aging are manifested precociously or in exacerbated form, has increased our knowledge of the molecular basis of aging. We have recently reported the unexpected finding that distinct progeroid murine models exhibit an extensive basal activation of autophagy instead of the characteristic decline in this process occurring during normal aging. Further studies on Zmpste24-null progeroid mice, which are a reliable model of human Hutchinson-Gilford progeria, have revealed that the observed autophagic increase is associated with a series of metabolic alterations resembling those occurring under calorie restriction or in other situations reported to prolong lifespan. Here, we analyze these unexpected findings and discuss their possible implications for the development of premature aging.
人们普遍认为，活细胞的自噬活性会随着年龄增长而降低，这可能是衰老过程中受损大分子和细胞器积累的原因。在过去几年中，对部分早衰综合征的研究增加了我们对衰老分子基础的认识，在这些综合征中，衰老的某些方面会过早或以加剧的形式表现出来。我们最近报告了一个意外发现，即不同的早衰小鼠模型表现出自噬的广泛基础激活，而不是正常衰老过程中该过程特有的下降。对Zmpste24基因敲除的早衰小鼠（这是人类哈钦森 - 吉尔福德早衰症的可靠模型）的进一步研究表明，观察到的自噬增加与一系列代谢改变有关，这些改变类似于在热量限制或其他据报道可延长寿命的情况下发生的改变。在这里，我们分析这些意外发现，并讨论它们对早衰发展的可能影响。
