Longo Valter D, Antebi Adam, Bartke Andrzej, Barzilai Nir, Brown-Borg Holly M, Caruso Calogero, Curiel Tyler J, de Cabo Rafael, Franceschi Claudio, Gems David, Ingram Donald K, Johnson Thomas E, Kennedy Brian K, Kenyon Cynthia, Klein Samuel, Kopchick John J, Lepperdinger Guenter, Madeo Frank, Mirisola Mario G, Mitchell James R, Passarino Giuseppe, Rudolph Karl L, Sedivy John M, Shadel Gerald S, Sinclair David A, Spindler Stephen R, Suh Yousin, Vijg Jan, Vinciguerra Manlio, Fontana Luigi
Davis School of Gerontology and Department of Biological Sciences, Longevity Institute, University of Southern California, Los Angeles, CA, 90089, USA.
IFOM, FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Milano, Italy.
Aging Cell. 2015 Aug;14(4):497-510. doi: 10.1111/acel.12338. Epub 2015 Apr 22.
The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR-S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.
题为“延缓人类衰老的干预措施:我们准备好了吗?”的研讨会于2013年10月8日至13日在意大利埃里切举行,旨在汇聚衰老生物学和遗传学领域的顶尖专家,就发现和开发安全的干预措施以延缓人类衰老、延长健康寿命达成共识。与会者一致认为,有充分证据表明衰老干预措施将延缓和预防许多成人及老年慢性疾病的发病。关键途径已被确定,行为、饮食和药物学方法也已出现。尽管讨论了许多基因靶点和药物,且并非对所有干预措施都完全达成共识,但与会者选择了一组最具前景的策略,可在人体中测试其对健康寿命的影响。这些策略包括:(i)模拟长期饮食限制的饮食干预措施(周期性禁食模拟饮食、蛋白质限制等);(ii)抑制生长激素/胰岛素样生长因子-I轴的药物;(iii)抑制mTOR-S6K途径的药物;或(iv)激活AMPK或特定去乙酰化酶的药物。这些选择部分基于这些干预措施在简单模型生物和啮齿动物中具有延长寿命作用、预防或延缓多种与年龄相关疾病以及改善健康寿命的一致证据,以及它们在延长人类健康寿命方面具有安全有效的潜力。本文的作者是受邀参加该研讨会的演讲者和讨论者。以下总结突出了会议讨论的要点和结论。