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. 2020 Nov 9;22(Suppl 2):ii221. doi: 10.1093/neuonc/noaa215.927

TAMI-39. AGE-DEPENDENT PHENOTYPIC CONVERSION FROM NEURONAL ACTIVITY TO NEURO-INFLAMMATION IN GLIOBLASTOMA PROGRESSION

Daisuke Yamashita 1, Victoria Flanary 2, Rachel Munk 3, Kazuhiro Sonomura 4, Saya Ozaki 1, Riki Kawaguchi 5, Satoshi Suehiro 1, Sadashib Ghosh 2, Zhihong Chen 6, Shinobu Yamaguchi 2, Svetlana Komarova 2, Soniya Bastola 2, Joshua Bernstock 7, Gwendalyn King 2, Dr Kunieda 1, Dolores Hambardzumyan 6, Toru Kondo 8, Harley Kornblum 5, David Crossman 2, James Hackney 2, Steve Horvath 5, Taka-aki Sato 4, Myriam Gorospe 3, Ichiro Nakano 2
PMCID: PMC7650979

Abstract

The rise in population aging worldwide is causing an unparalleled increase in death from many cancers, including glioblastoma (GBM). Here, we have explored the impact of aging and rejuvenation on GBM tumorigenesis. Compared with neuro-inflammatory old GBM, young GBM displayed elevated neuronal/synaptic signaling via brain-derived neurotrophic factor (BDNF) and SLIT and NTRK like-family member 6 (SLITRK6), promoting favorable survival rates. These effects were attributed to the rise in nicotinamide adenine dinucleotide (NAD+) levels, as brain rejuvenation by parabiosis or administration of nicotinamide mononucleotide (NMN) in mice elicited a younger phenotype with activated neuronal/synaptic signaling and improved outcomes. Our data indicate that age-associated NAD+ loss contributes to the highly aggressive GBM by the shift from neuronal/synaptic activity to neuro-inflammation in the elderly brain. These findings have therapeutic and preventive implications in GBM and provide mechanistic insights into the exacerbation of GBM tumorigenesis by aging.


Articles from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Oxford University Press

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