Worldwide, people are getting older, and this prolonged lifespan unfortunately also results in an increased prevalence of age-related neurodegenerative diseases, contributing to a diminished life quality of elderly. Age-associated neuropathies typically include diseases leading to dementia (Alzheimer’s and Parkinson’s disease), as well as eye diseases such as glaucoma and age-related macular degeneration. Despite many research attempts aiming to unravel aging processes and their involvement in neurodegeneration and functional decline, achieving healthy brain aging remains a challenge. The African turquoise killifish (Nothobranchius furzeri) is the shortest-lived reported vertebrate that can be bred in captivity and displays many of the aging hallmarks that have been described for human aging, which makes it a very promising biogerontology model. As vision decline is an important hallmark of aging as well as a manifestation of many neurodegenerative diseases, we performed a comprehensive characterization of this fish’s aging visual system. Our work reveals several aging hallmarks in the killifish retina and brain that eventually result in a diminished visual performance. Moreover, we found evidence for the occurrence of neurodegenerative events in the old killifish retina. Altogether, we introduce the visual system of the fast-aging killifish as a valuable model to understand the cellular and molecular mechanisms underlying aging in the vertebrate central nervous system. These findings put forward the killifish for target validation as well as drug discovery for rejuvenating or neuroprotective therapies ensuring healthy aging.

在世界范围内，人们正在变老，不幸的是，寿命的延长也导致与年龄相关的神经退行性疾病的患病率增加，导致老年人的生活质量下降。与年龄相关的神经病通常包括导致痴呆的疾病（阿尔茨海默病和帕金森病），以及眼部疾病，例如青光眼和与年龄相关的黄斑变性。尽管许多研究试图揭示衰老过程及其与神经退行性变和功能衰退的关系，但实现健康的大脑衰老仍然是一个挑战。非洲绿松石鳉鱼（Nothobranchiusfurzeri）是已知的寿命最短的脊椎动物，可以圈养繁殖，并表现出许多人类衰老的特征，这使其成为一种非常有前途的生物老年学模型。由于视力下降是衰老的重要标志，也是许多神经退行性疾病的表现，因此我们对这种鱼的衰老视觉系统进行了全面的表征。我们的工作揭示了鳉鱼视网膜和大脑中的几个衰老特征，这些特征最终导致视觉性能下降。此外，我们还发现了老鳉鱼视网膜中发生神经退行性事件的证据。总而言之，我们介绍了快速衰老的鳉鱼的视觉系统，作为了解脊椎动物中枢神经系统衰老的细胞和分子机制的有价值的模型。这些发现提出了将鳉鱼用于目标验证以及药物发现，以确保健康衰老的恢复活力或神经保护疗法。