Opportunities for organoids as new models of aging

Abstract

The biology of aging is challenging to study, particularly in humans. As a result, model organisms are used to approximate the physiological context of aging in humans. However, the best model organisms remain expensive and time-consuming to use. More importantly, they may not reflect directly on the process of aging in people. Human cell culture provides an alternative, but many functional signs of aging occur at the level of tissues rather than cells and are therefore not readily apparent in traditional cell culture models. Organoids have the potential to effectively balance between the strengths and weaknesses of traditional models of aging. They have sufficient complexity to capture relevant signs of aging at the molecular, cellular, and tissue levels, while presenting an experimentally tractable alternative to animal studies. Organoid systems have been developed to model many human tissues and diseases. Here we provide a perspective on the potential for organoids to serve as models for aging and describe how current organoid techniques could be applied to aging research.

Figure 1.

Types of organoids. (A) Tissue fragments and explants are generated from native tissue with little disruption to cell and ECM organization and no intermediate period in 2D culture. This limits total sample size and manipulability but is unmatched in mimicking the original tissue. (B) Reconstituted organoids are assembled in vitro from cultured or sorted cells. This permits cell expansion and modular assembly of components. However, some subpopulations or phenotypes, such as senescent and hormone-responsive cells, may be lost during culture. (C) Stem cell–derived organoids are differentiated from multipotent adult tissue stem cells or PSCs under the appropriate differentiation and maintenance conditions. PSCs specifically can generate rare tissue and cell types, but have limited maturity and lose the hallmarks of aging.