The traditional view considered forgetting as a passive process where memory traces gradually fade due to the natural weakening of neural connections. However, studies on olfactory memory in Drosophila have revealed that forgetting is an active process controlled by specific neural circuits. Caenorhabditis elegans is a widely used model organism in neurobiological research due to its relatively simple nervous system. Despite its simplicity C. elegans exhibits complex behaviors influenced by environmental factors and prior experiences. Similar to Drosophila, C. elegans can actively initiate neural circuits based on the type of memory that needs to be forgotten, which supports using C. elegans as a model for studying forgetting. These characteristics facilitate the identification of genes and pathways involved in forgetting in C. elegans. In this review, we discuss recent advances in understanding forgetting mechanisms in C. elegans through three well-characterized olfactory learning paradigms. The insights derived from C. elegans offer a valuable framework for understanding the molecular and cellular mechanisms underlying forgetting, with potentially broader implications for memory regulation in more complex organisms.

Dementia constitutes a significant public health crisis, accounting for one-third of deaths among the elderly and exceeding the combined mortality of breast and prostate cancers. Alzheimer's disease (AD), the predominant form of dementia (60–70%), primarily manifests as late-onset AD (LOAD), which constitutes over 95% of all AD cases. The risk of developing LOAD escalates dramatically with age, affecting approximately half of individuals over 85 years of age, thus positioning LOAD as a critical age-related medical challenge. The present study proposes a novel conceptual framework for understanding LOAD, positing it not merely as a discrete disease but rather as a maladaptive trajectory of brain aging, in which physiological aging processes progressively evolve into pathological states. This transition is driven by synergistic interactions between genetic susceptibility, environmental exposures, and aging-related mechanisms, with epigenetic alterations serving as a central dynamic mediator. This analysis demonstrates that genetic factors, aging, and environmental influences collectively regulate LOAD susceptibility through a multidimensional interplay: while genes directly drive pathological pathways, their expression is dynamically modulated by age and environmental context via epigenetic mechanisms. Deciphering these complex interactions provides crucial insights into LOAD pathogenesis. This reconceptualisation necessitates a paradigm shift in therapeutic strategy. Rather than focusing exclusively on amyloid-centric approaches, we advocate targeting core aging mechanisms to enhance brain resilience. The most promising interventions aim to counteract maladaptive cognitive decline by improving proteostasis, modulating epigenetic drivers, and suppressing chronic neuroinflammation. This would reposition healthy brain aging as the cornerstone of LOAD prevention and treatment.

随着人口老龄化速度加快，我国以阿尔茨海默病为主的老年痴呆发病人数持续增加。多项研究证据表明糖摄入量过高是患阿尔茨海默的重要风险因子之一。随着零糖零卡健康生活方式提出，天然甜味剂因安全性高、低热量和代谢方式简单等优点被广泛应用于食品和医药行业。然而，天然甜味剂作为糖替代品在食品中添加是否能有效降低患阿尔茨海默的风险？为评估目前常用的天然甜味剂对阿尔茨海默的影响，本研究应用AD（Alzheimer's disease）线虫模型对7个目标甜味剂进行筛选。得到的主要研究结果如下：根皮苷、罗汉果苷、甜茶苷、甜菊糖苷、赤藓糖醇能有效延缓CL4176麻痹、改善CL2355学习缺陷；D-阿洛酮糖加速CL4176麻痹，且未能改善CL2355学习缺陷；木糖醇作用效果不明显。本研究进行为天然甜味剂的安全使用提供理论依据。