Clinical Trials Targeting Aging.
Clinical Trials Targeting Aging.
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DOI：
10.3389/fragi.2022.820215
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发表时间：
2022
影响因子：
--
通讯作者：
Scheibye-Knudsen, Morten
中科院分区：
文献类型：
--
作者：
Nielsen, Johannes Leth;Bakula, Daniela;Scheibye-Knudsen, Morten
发病率和死亡率的风险随着年龄的增长呈指数级增长。慢性炎症、DNA损伤的积累、线粒体功能障碍和衰老细胞负荷增加是导致这种情况的因素。机制研究已经揭示了特定的途径和过程，这可能导致与年龄相关的表型，如虚弱，身体弹性降低和多发病率。缓解衰老后果的有希望的治疗方法包括热量限制和靶向长寿途径的抑制剂，如雷帕霉素（mTOR）的机制靶点，sirtuins和衰老细胞中的抗凋亡途径。这些途径和过程的调节在动物模型中显示出显著的健康和寿命延长结果。然而，目前还不清楚类似的结果是否适用于人类。翻译的要求是开发年龄和发病率相关的生物标志物，因为当人类寿命为终点时，纵向试验是困难的，不可行，不实用，也不符合伦理。目前的生物标志物和人类抗衰老干预研究的结果将涵盖在本文中。如果研究药物的安全性和耐受性继续不成为进一步研究的障碍，则针对衰老的临床试验的未来可能是具有更大人群的2期和3期研究。
The risk of morbidity and mortality increases exponentially with age. Chronic inflammation, accumulation of DNA damage, dysfunctional mitochondria, and increased senescent cell load are factors contributing to this. Mechanistic investigations have revealed specific pathways and processes which, proposedly, cause age-related phenotypes such as frailty, reduced physical resilience, and multi-morbidity. Among promising treatments alleviating the consequences of aging are caloric restriction and pharmacologically targeting longevity pathways such as the mechanistic target of rapamycin (mTOR), sirtuins, and anti-apoptotic pathways in senescent cells. Regulation of these pathways and processes has revealed significant health- and lifespan extending results in animal models. Nevertheless, it remains unclear if similar results translate to humans. A requirement of translation are the development of age- and morbidity associated biomarkers as longitudinal trials are difficult and not feasible, practical, nor ethical when human life span is the endpoint. Current biomarkers and the results of anti-aging intervention studies in humans will be covered within this paper. The future of clinical trials targeting aging may be phase 2 and 3 studies with larger populations if safety and tolerability of investigated medication continues not to be a hurdle for further investigations.
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影响因子：
15.8
作者：
Civitarese AE;Carling S;Heilbronn LK;Hulver MH;Ukropcova B;Deutsch WA;Smith SR;Ravussin E;CALERIE Pennington Team
通讯作者：
CALERIE Pennington Team
影响因子：
37.8
作者：
Diguet N;Trammell SAJ;Tannous C;Deloux R;Piquereau J;Mougenot N;Gouge A;Gressette M;Manoury B;Blanc J;Breton M;Decaux JF;Lavery GG;Baczkó I;Zoll J;Garnier A;Li Z;Brenner C;Mericskay M
通讯作者：
Mericskay M
影响因子：
7.8
作者：
Fiorito G;Caini S;Palli D;Bendinelli B;Saieva C;Ermini I;Valentini V;Assedi M;Rizzolo P;Ambrogetti D;Ottini L;Masala G
通讯作者：
Masala G
影响因子：
7.1
作者：
Dollerup, Ole L.;Christensen, Britt;Jessen, Niels
通讯作者：
Jessen, Niels
影响因子：
20.8
作者：
Covarrubias AJ;Kale A;Perrone R;Lopez-Dominguez JA;Pisco AO;Kasler HG;Schmidt MS;Heckenbach I;Kwok R;Wiley CD;Wong HS;Gibbs E;Iyer SS;Basisty N;Wu Q;Kim IJ;Silva E;Vitangcol K;Shin KO;Lee YM;Riley R;Ben-Sahra I;Ott M;Schilling B;Scheibye-Knudsen M;Ishihara K;Quake SR;Newman J;Brenner C;Campisi J;Verdin E
通讯作者：
Verdin E