Table 1.

Strategies to improve the maturation and model aging in in brain organoid cultures.

	Benefits	Limitations	References
Prolonged culture periods (more than 250 days)	Mature synapses, dendritic spines and network dynamics. Proper glia differentiation Enable the myelination process	Increases the cost of production and reduces reproducibility	Quadrato et al. (2016)
Co-culture with other cell types	Favours maturation of neurons and circuits formation	Technically challenging, considering different cell types with different proliferation and differentiation rhythms	Bhaduri et al. (2020)
Genetic engineering	Control of proliferation, differentiation and maturation processes in hIPSC	Altered cell physiology inappropriate in translational medicine	Miller et al. (2013), Li et al. (2017), and Ma et al. (2022)
Pharmacological or environmental strategies	Allows induction of aging in hIPSC	Alterations of the natural and physiological cellular mechanisms	Vera et al. (2016) and Kim et al. (2019a,b)