Effects of minocycline and rapamycin in gamma-irradiated human embryonic stem cells-derived cerebral organoids

Cellular reprogramming as a tool to model human aging in a dish

“…Recent studies have used organoids to study cellular aging 14 , 102 , 103 and to identify treatments to ameliorate age-related diseases 104 , 105 . For example, brain organoids generated from iPSCs isolated from patients suffering from ataxia-telangiectasia (carrying a mutation in the ataxia-telangiectasia-mutated (ATM) gene that encodes the ATM kinase) have been used to investigate the impact of ATM kinase absence in the nervous system 14 .…”

“…Importantly, inhibition of cGAS and STING-dependent inflammation effectively suppressed self-DNA-induced SASP activation and rescued the neuropathological features in brain organoids. In a separate study, brain organoids generated from AD iPSC-derived cells or γ-irradiated brain organoids generated from wild-type cells, have been also used to screen drugs 104 , 105 . Moreover, aged colon organoids were obtained from human iPSCs to investigate whether DNA damage response was inversely correlated with an increase in the production of growth hormone 102 .…”

Strategies for modeling aging and age-related diseases

“…This led to the finding that the activation of the cGAS-STING pathway, a part of the immune response, leads to premature cellular aging. Furthermore, cerebral organoids derived from iPSCs irradiated with gamma radiation to induce cell damage followed by the investigation of whether anti-aging substances minocycline and rapamycin play a role in cell viability, proliferation, and differentiation 25 . It was identified that the pre-conditioning of neurospheres to rapamycin before irradiation and to minocycline after irradiation confers neuroprotection and rescues developmental potential of the cerebral organoid.…”