Finding Ponce de Leon's Pill: Challenges in Screening for Anti-Aging Molecules.
Finding Ponce de Leon's Pill: Challenges in Screening for Anti-Aging Molecules.
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DOI：
10.12688/f1000research.7821.1
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Lombard, David B
中科院分区：
文献类型：
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作者：
Kumar, Surinder;Lombard, David B
衰老的特征是退行性变化的渐进性积累，最终导致功能受损和死亡概率增加。它是许多人类疾病--包括癌症、2型糖尿病、心血管和神经退行性疾病--的主要风险因素，因此会造成巨大的社会和经济损失。老龄化研究的主要目标是开发干预措施，以延迟多种与年龄相关的疾病的发生，延长健康寿命(Health Span)。通过饮食限制或简单的基因操作可以在模式生物中实现延长寿命和健康的观察结果，促使人们寻找可以延长寿命的化合物。大多数调节哺乳动物衰老速度的途径在酵母、苍蝇和蠕虫中都有同源基因，这表明使用无脊椎动物模型进行初步筛选以确定这种药物干预是可能的。近年来，已发现几种化合物可以延长无脊椎动物的寿命，甚至可以延长啮齿类动物的寿命。在这里，我们总结了在从无脊椎动物到老鼠的各种生物中识别能够延长寿命的化合物方面所采用的策略和取得的进展，并讨论了将这项工作转化为人类疗法的艰巨挑战。
Aging is characterized by the progressive accumulation of degenerative changes, culminating in impaired function and increased probability of death. It is the major risk factor for many human pathologies - including cancer, type 2 diabetes, and cardiovascular and neurodegenerative diseases - and consequently exerts an enormous social and economic toll. The major goal of aging research is to develop interventions that can delay the onset of multiple age-related diseases and prolong healthy lifespan (healthspan). The observation that enhanced longevity and health can be achieved in model organisms by dietary restriction or simple genetic manipulations has prompted the hunt for chemical compounds that can increase lifespan. Most of the pathways that modulate the rate of aging in mammals have homologs in yeast, flies, and worms, suggesting that initial screening to identify such pharmacological interventions may be possible using invertebrate models. In recent years, several compounds have been identified that can extend lifespan in invertebrates, and even in rodents. Here, we summarize the strategies employed, and the progress made, in identifying compounds capable of extending lifespan in organisms ranging from invertebrates to mice and discuss the formidable challenges in translating this work to human therapies.