Charles River Laboratories, Wilmington, MA, United States; CNS Biology, Takeda, San Diego, CA, United States.
Departments of Biochemistry and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Buck Institute for Research on Aging, Novato, CA, United States.
Neurosci Biobehav Rev. 2020 Jan;108:453-458. doi: 10.1016/j.neubiorev.2019.11.021. Epub 2019 Nov 26.
Increased healthcare and pharmaceutical understanding has led to the eradication of many childhood, infectious and preventable diseases; however, we are now experiencing the impact of aging disorders as the lifespan increases. These disorders have already become a major burden on society and threaten to become a defining challenge of our generation. Indications such as Alzheimer's disease gain headlines and have focused the thinking of many towards dementia and cognitive decline in aging. Indications related to neurological function and related behaviors are thus an extremely important starting point in the consideration of therapeutics.However, the reality is that pathological aging covers a spectrum of significant neurological and peripheral indications. Development of therapeutics to treat aging and age-related disorders is therefore a huge need, but represents a largely unexplored path. Fundamental scientific questions need to be considered as we embark towards a goal of improving health in old age, including how we 1) define aging as a therapeutic target, 2) model aging preclinically and 3) effectively translate from preclinical models to man. Furthermore, the challenges associated with identifying novel therapeutics in a financial, regulatory and clinical sense need to be contemplated carefully to ensure we address the unmet need in our increasingly elderly population. The complexity of the challenge requires different perspectives, cross-functional partnerships and diverse concepts. We seek to raise issues to guide the field, considering the current state of thinking to aid in identifying roadblocks and important challenges early. The need for therapeutics that address aging and age-related disorders is acute, but the promise of effective treatments provides huge opportunities that, as a community, we all seek to enable effectively as soon as possible.
医疗卫生和制药领域知识的增长使得许多儿童期传染病和可预防疾病得以消除;然而,随着寿命的延长,我们现在正面临与衰老相关疾病的影响。这些疾病已经成为社会的主要负担,并有可能成为我们这一代人的一个决定性挑战。阿尔茨海默病等疾病的出现成为头条新闻,促使许多人关注衰老过程中的痴呆和认知能力下降。因此,与神经功能和相关行为相关的疾病是考虑治疗方法的一个极其重要的起点。然而,事实上,病理性衰老涵盖了一系列重要的神经和外周疾病。因此,开发治疗衰老和与年龄相关疾病的疗法是一项巨大的需求,但这也是一条尚未得到充分探索的道路。在我们努力实现老年健康的目标时,需要考虑一些基本的科学问题,包括我们如何 1)将衰老定义为治疗靶点,2)在临床前模拟衰老,以及 3)将其从临床前模型有效地转化为人类。此外,还需要仔细考虑在财务、监管和临床方面识别新疗法的相关挑战,以确保我们满足日益老龄化人口的未满足需求。挑战的复杂性需要不同的观点、跨职能的合作关系和多样化的理念。我们旨在提出问题以指导该领域,考虑当前的思维状态,以帮助尽早识别障碍和重要挑战。治疗衰老和与年龄相关疾病的疗法需求迫切,但有效的治疗方法的前景提供了巨大的机会,作为一个社区,我们都希望尽快有效地实现这些机会。