Ridderinkhof K Richard, Krugers Harm J
Department of Psychology, University of Amsterdam, Amsterdam, Netherlands.
Amsterdam Center for Brain and Cognition (ABC), University of Amsterdam, Amsterdam, Netherlands.
Front Hum Neurosci. 2022 Jun 29;16:815759. doi: 10.3389/fnhum.2022.815759. eCollection 2022.
While aging is an important risk factor for neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, age-related cognitive decline can also manifest without apparent neurodegenerative changes. In this review, we discuss molecular, cellular, and network changes that occur during normal aging in the absence of neurodegenerative disease. Emerging findings reveal that these changes include metabolic alterations, oxidative stress, DNA damage, inflammation, calcium dyshomeostasis, and several other hallmarks of age-related neural changes that do not act on their own, but are often interconnected and together may underlie age-related alterations in brain plasticity and cognitive function. Importantly, age-related cognitive decline may not be reduced to a single neurobiological cause, but should instead be considered in terms of a densely connected system that underlies age-related cognitive alterations. We speculate that a decline in one hallmark of neural aging may trigger a decline in other, otherwise thus far stable subsystems, thereby triggering a cascade that may at some point also incur a decline of cognitive functions and mental well-being. Beyond studying the effects of these factors in isolation, considerable insight may be gained by studying the larger picture that entails a representative collection of such factors and their interactions, ranging from molecules to neural networks. Finally, we discuss some potential interventions that may help to prevent these alterations, thereby reducing cognitive decline and mental fragility, and enhancing mental well-being, and healthy aging.
虽然衰老对于诸如阿尔茨海默病和帕金森病等神经退行性疾病来说是一个重要的风险因素，但与年龄相关的认知衰退也可能在没有明显神经退行性变化的情况下出现。在这篇综述中，我们讨论了在没有神经退行性疾病的正常衰老过程中发生的分子、细胞和网络变化。新出现的研究结果表明，这些变化包括代谢改变、氧化应激、DNA损伤、炎症、钙稳态失调以及其他一些与年龄相关的神经变化特征，这些变化并非单独起作用，而是常常相互关联，共同构成了与年龄相关的大脑可塑性和认知功能改变的基础。重要的是，与年龄相关的认知衰退可能不能归结于单一的神经生物学原因，而应从一个紧密相连的系统角度来考虑，这个系统是与年龄相关的认知改变的基础。我们推测，神经衰老的一个特征的衰退可能会引发其他原本稳定的子系统的衰退，从而引发一系列连锁反应，在某个时候可能还会导致认知功能和心理健康的下降。除了单独研究这些因素的影响之外，通过研究包含这些因素及其相互作用的代表性集合（从分子到神经网络）的整体情况，可能会获得相当多的见解。最后，我们讨论了一些可能有助于预防这些改变的潜在干预措施，从而减少认知衰退和心理脆弱性，增强心理健康和健康老龄化。
