Wise John P
NeuroWise Laboratory of Environmental Neurotoxicology, Pediatrics Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, United States.
Front Aging. 2022 Sep 21;3:1014675. doi: 10.3389/fragi.2022.1014675. eCollection 2022.
We are imminently faced with the challenges of an increasingly aging population and longer lifespans due to improved health care. Concomitantly, we are faced with ubiquitous environmental pollution linked with various health effects and age-related diseases which contribute to increased morbidity with age. Geriatric populations are rarely considered in the development of environmental regulations or in toxicology research. Today, life expectancy is often into one's 80s or beyond, which means multiple decades living as a geriatric individual. Hence, adverse health effects and late-onset diseases might be due to environmental exposures as a geriatric, and we currently have no way of knowing. Considering aging from a different perspective, the term "gerontogen" was coined in 1987 to describe chemicals that accelerate biological aging but has largely been left out of toxicology research. Thus, we are challenged with a two-faced problem that we can describe as a "toxic aging coin"; on one side we consider how age affects the toxic outcome of chemicals, whereas on the other side we consider how chemicals accelerate aging (i.e. how chemicals act as gerontogens). Conveniently, both sides of this coin can be tackled with a single animal study that considers multiple age groups and assesses basic toxicology of the chemical(s) tested and aging-focused endpoints. Here, I introduce the concept of this toxic aging coin and some key considerations for how it applies to toxicology research. My discussion of this concept will focus on the brain, my area of expertise, but could be translated to any organ system.
由于医疗保健的改善，我们正迫切面临人口老龄化加剧和寿命延长的挑战。与此同时，我们面临着无处不在的环境污染，它与各种健康影响和与年龄相关的疾病有关，这些疾病会导致随着年龄增长发病率上升。在环境法规的制定或毒理学研究中，很少考虑老年人群体。如今，预期寿命常常能达到80多岁甚至更长，这意味着要作为老年人生活数十年。因此，不良健康影响和迟发性疾病可能是由于老年时的环境暴露所致，而我们目前对此一无所知。从不同角度看待衰老，“老年源”一词于1987年被创造出来，用于描述加速生物衰老的化学物质，但在很大程度上被排除在毒理学研究之外。因此，我们面临着一个可以被描述为“有毒衰老硬币”的双面问题；一方面，我们考虑年龄如何影响化学物质的毒性结果，而另一方面，我们考虑化学物质如何加速衰老（即化学物质如何作为老年源起作用）。方便的是，这枚硬币的两面都可以通过一项考虑多个年龄组并评估所测试化学物质的基本毒理学和以衰老为重点的终点的单一动物研究来解决。在此，我介绍这个有毒衰老硬币的概念以及它如何应用于毒理学研究的一些关键考虑因素。我对这个概念的讨论将聚焦于大脑，这是我的专业领域，但也可以推广到任何器官系统。
