A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer’s disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-β and tau pathologies, and improved the animals’ memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational–experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis.

Oral lichen planus (OLP) is a chronic mucosal inflammatory disease. The World Health Organization has described it as a potentially malignant condition. The pathogenesis of OLP remains to be fully elucidated, but extensive evidence suggests that immunologic and inflammatory factors have important roles. MicroRNAs (miRs), which are small non-coding RNAs, have been reported to be involved in OLP. In particular, miR-155 is significantly upregulated in patients with OLP. miR-155 has numerous functions and is closely linked to inflammation and immune system regulation. However, in-depth studies of the mechanisms via which miR-155 is involved in OLP are currently insufficient. Considering the close association between miR-155 and immune regulation as well as the importance of immune factors in OLP, the role of miR-155 in the immune system was herein summarized with a focus on OLP. The present review provides a basis for further study of the molecular mechanisms underlying the development and progression of OLP.

Oral potentially malignant disorders (OPMD) develop in a complex tissue microenvironment where they grow sustainably, acquiring oral squamous cell carcinoma (OSCC) characteristics. The malignant tumor depends on interactions with the surrounding microenvironment to achieve loco-regional invasion and distant metastases. Unlike abnormal cells, the multiple cell types in the tissue microenvironment are relatively stable at the genomic level and, thus, become therapeutic targets with lower risk of resistance, decreasing the risk of OPMD acquiring cancer characteristics and carcinoma recurrence. However, deciding how to disrupt the OPMD and OSCC microenvironments is itself a daunting challenge, since their microenvironments present opposite capacities, resulting in diverse consequences. Furthermore, recent studies revealed that tumor-associated immune cells also participate in the process of differentiation from OPMD to OSCC, suggesting that reeducating stromal cells may be a new strategy to prevent OPMD from acquiring OSCC characteristics and to treat OSCC. In this review, we discuss the characteristics of the microenvironment of OPMD and OSCC as well as new therapeutic strategies.

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Since its introduction as a genetic model organism, Caenorhabditis elegans has yielded insights into the causes of aging. In addition, it has provided a molecular understanding of mechanisms of neurodegeneration, one of the devastating effects of aging. However, C. elegans has been less popular as an animal model to investigate DNA repair and genomic instability, which is a major hallmark of aging and also a cause of many rare neurological disorders. This article provides an overview of DNA repair pathways in C. elegans and the impact of DNA repair on aging hallmarks, such as mitochondrial dysfunction, telomere maintenance, and autophagy. In addition, we discuss how the combination of biological characteristics, new technical tools, and the potential of following precise phenotypic assays through a natural life-course make C. elegans an ideal model organism to study how DNA repair impact neurodegeneration in models of common age-related neurodegenerative diseases.

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Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery (ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community.