Sex Differences in Mouse Longevity and Responses to Geroprotective Drugs: Implications for Human Intervention.
Sex Differences in Mouse Longevity and Responses to Geroprotective Drugs: Implications for Human Intervention.
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小鼠寿命的性别差异和对老年保护药物的反应：对人类干预的影响。
DOI：
10.1093/ppar/prad026
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Nelson,JamesF
中科院分区：
文献类型：
--
作者：
Jiang,Nisi;Nelson,JamesF
从生物学上讲，衰老的过程涉及到一个人一生中分子、细胞和生理过程的变化，这些变化会导致功能能力的丧失、韧性的降低、健康的下降和死亡的可能性增加。然而，较少被认识到的是其他过程，如学习和记忆，在没有神经退行性疾病的情况下，这些过程使经验和韧性得以积累。老龄化的这些好处和其他好处导致了“长寿红利”的重要概念(Olshansky等人，2007年)。找出既能最大限度地减少老龄化的负面影响，又能最大限度地发挥老龄化积极作用的方法，应该推动一项不仅有利于个人，也有利于更大范围的社区，并最终惠及整个社会的政策。在这里，我们提供一些关于衰老性别差异的生物学研究如何有助于制定政策，使我们的生活随着年龄的增长更健康、更有意义的努力的一些观点。无论衰老过程的某个特定组成部分具有积极或消极的影响，其变化的速度、幅度和性质都存在显著的性别差异(Austad&Fischer，2016；Mauvais-Jarvis等人，2020)。因此，我们必须保持警惕，努力了解构成这些差异的生物机制中的性别差异，以及潜在的文化和环境因素。努力制定政策，使我们所有人都能随着年龄的增长拥有更有意义和更健康的生活，需要承认和应对这些性别差异，以确保妇女和男子都能从政策变化和执行中获得同样的好处。例如，直到最近，药物有效性和安全性的临床试验主要在男性身上进行，这可能是女性药物不良反应发生率较高的原因(Madla等人，2021年)。显然，研究政策应该更多地强调理解性别差异，这反过来可以改善基于证据的政策制定。虽然我们的重点是性别差异背后的生物学因素，但同样的论点也适用于研究环境和文化因素，这些因素导致了年龄增长的性别差异。本文的第一个目的是概述人类衰老过程中的主要性别差异，然后介绍一个在衰老过程中显示类似性别差异的动物模型。需要这样的动物模型来发现性别差异的生物学基础，因为它可以通过实验进行研究。还将举例说明其在解释衰老过程中性别差异的生物学机制方面的作用。然后，我们将描述在这个动物模型中测试的一些治疗干预措施，这些干预措施显示出延长健康寿命和改善衰老的一些有害方面的希望。我们将强调这些干预措施在效果上的显著性别差异，这再次强调了在我们所有的研究努力和政策制定中认识到性别是一个关键变量的重要性。尽管已经提出了许多理论，并在确定衰老的潜在原因方面取得了巨大进展，但它们的相对重要性仍然没有得到很好的理解(Bengtson&Settersten，2016)。即使是用科学可衡量的方式来定义衰老也是具有挑战性的。人口统计指标，如人口的平均寿命和最长寿命，以及死亡率随年龄增长的速度，包括一种评估保护老年人的干预措施是否有效或一个人口的老龄化速度是否比另一个人口更快的方法。事实上，人类衰老中性别差异的最明显例子之一是中位寿命，这是…
The process of aging, biologically speaking, involves changes in molecular, cellular, and physiological processes over the life course of an individual that lead to losses in functional capacities, reduced resilience, decreased health, and increased vulnerability to death. Less recognized, however, are other processes such as learning and memory, which, in the absence of neurodegenerative disease, enable the accrual of experience and resilience. These and other benefits of aging have led to the important concept of the “longevity dividend”(Olshansky e t al., 2007). Identifying ways both to minimize the negative and maximize the positive aspects of aging should drive policy that will benefit not only the individual but the larger community and ultimately, society at large. Here we offer some perspectives on how biological research on sex differences in aging can contribute to developing policies that better serve efforts in make lives healthier and more meaningful as we grow older. Whether a particular component of the aging process has positive or negative ramifications, there are marked sex differences in its rate, magnitude, and nature of change (Austad & Fischer, 2016; Mauvais-Jarvis et al., 2020). We must therefore be alert and seek to understand the sex differences in the biological mechanisms that underlie them, as well as the underlying cultural and environmental factors. Efforts to develop policies that enable all of us to have more meaningful and healthier lives as we grow older need to recognize and respond to these sex differences to ensure that both women and men achieve the same benefits of policy changes and implementation. Clinical trials of drugs for efficacy and safety, for example, until recently were mainly conducted in men, which likely underlies the higher incidence of adverse drug reactions in women (Madla et al., 2021). Clearly, research policy should put more emphasis on understanding sex differences, which can in turn improve evidence-based policymaking. Although our focus is on the biological factors underlying sex differences, the same arguments hold for studying environmental and cultural factors that contribute to sex differences in aging. The first aim of this article is to provide an overview of major sex differences in human aging and then introduce an animal model that shows similar sex differences during aging. Such an animal model is needed to discover the biological basis for those sex differences, because it can be studied experimentally. Examples of its utility for elucidating the biological mechanisms responsible for sex differences in aging will be given. We will then describe some of the therapeutic interventions tested in this animal model that show promise for extending healthy lifespan and ameliorating some of the deleterious aspects of aging. We will highlight the remarkable sex differences in the efficacy of those interventions, which again underscore the importance of recognizing sex as a key variable in all our research endeavors and policymaking. Although many theories have been proposed and enormous strides have been made in identifying potential causes of aging, their relative importance is still not well understood (Bengtson & Settersten, 2016). Even defining aging in a scientifically measurable way is challenging. Demographic measures, such as the average and maximal lifespan of a population and the rate at which mortality increases with chronological age, comprise one way to assess whether geroprotective interventions are working or whether one population is aging more rapidly than another. Indeed, one of the clearest examples of sex difference in human aging is the median lifespan, which …
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影响因子：
2.4
作者：
Brayton, C. F.;Treuting, P. M.;Ward, J. M.
通讯作者：
Ward, J. M.
作为衰老研究模型的外来小鼠：争论和招股说明书。
影响因子：
4.2
作者：
Miller,RA;Austad,S;Burke,D;Chrisp,C;Dysko,R;Galecki,A;Jackson,A;Monnier,V
通讯作者：
Monnier,V
DOI：
--
发表时间：
2016
期刊：
影响因子：
--
作者：
V. Bengtson;R. Settersten;B. Kennedy;N. Morrow;Jacqui Smith
通讯作者：
Jacqui Smith
影响因子：
29
作者：
Austad SN;Fischer KE
通讯作者：
Fischer KE
影响因子：
5.2
作者：
S. Olshansky;D. Perry;Richard A. Miller;R. Butler
通讯作者：
R. Butler