Accelerated neuronal aging in vitro ∼melting watch ∼

Abstract

In developed countries, the aging of the population and the associated increase in age-related diseases are causing major unresolved medical, social, and environmental matters. Therefore, research on aging has become one of the most important and urgent issues in life sciences. If the molecular mechanisms of the onset and progression of neurodegenerative diseases are elucidated, we can expect to develop disease-modifying methods to prevent neurodegeneration itself. Since the discovery of induced pluripotent stem cells (iPSCs), there has been an explosion of disease models using disease-specific iPSCs derived from patient-derived somatic cells. By inducing the differentiation of iPSCs into neurons, disease models that reflect the patient-derived pathology can be reproduced in culture dishes, and are playing an active role in elucidating new pathological mechanisms and as a platform for new drug discovery. At the same time, however, we are faced with a new problem: how to recapitulate aging in culture dishes. It has been pointed out that cells differentiated from pluripotent stem cells are juvenile, retain embryonic traits, and may not be fully mature. Therefore, attempts are being made to induce cell maturation, senescence, and stress signals through culture conditions. It has also been reported that direct conversion of fibroblasts into neurons can reproduce human neurons with an aged phenotype. Here, we outline some state-of-the-art insights into models of neuronal aging in vitro. New frontiers in which stem cells and methods for inducing differentiation of tissue regeneration can be applied to aging research are just now approaching, and we need to keep a close eye on them. These models are forefront and intended to advance our knowledge of the molecular mechanisms of aging and contribute to the development of novel therapies for human neurodegenerative diseases associated with aging.

Fountain of youth—Targeting autophagy in aging

“…Considering that aging is an incredibly complex and not yet fully understood process, an in vitro model which can preserve the genotype and the aging phenotype of the donor would be beneficiary to study neuronal autophagy during human aging in detail ( Torrent et al, 2015 ; Mertens et al, 2018 ). Direct cellular reprogramming, a relatively novel technique can potentially overcome some of the limitations of currently well-known and widely used cellular reprogramming techniques in studying neuronal aging in vitro ( Drouin-Ouellet et al, 2017 ; Inagaki et al, 2022 ; Figure 1C ). During direct neural reprogramming, cells are being transdifferentiated into induced neurons (iNs) without going through a pluripotent or progenitor phase by using a combination of proneuronal transcription factors, microRNAs, growth factors and chemical compounds.…”