| First Author | Burns JC | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32579115 | Mgi Jnum | J:292138 |
| Mgi Id | MGI:6445477 | Doi | 10.7554/eLife.57495 |
| Citation | Burns JC, et al. (2020) Differential accumulation of storage bodies with aging defines discrete subsets of microglia in the healthy brain. Elife 9:e57495 |
| abstractText | To date, microglia subsets in the healthy CNS have not been identified. Utilizing autofluorescence (AF) as a discriminating parameter, we identified two novel microglia subsets in both mice and non-human primates, termed autofluorescence-positive (AF(+)) and negative (AF(-)). While their proportion remained constant throughout most adult life, the AF signal linearly and specifically increased in AF(+) microglia with age and correlated with a commensurate increase in size and complexity of lysosomal storage bodies, as detected by transmission electron microscopy and LAMP1 levels. Post-depletion repopulation kinetics revealed AF(-) cells as likely precursors of AF(+) microglia. At the molecular level, the proteome of AF(+) microglia showed overrepresentation of endolysosomal, autophagic, catabolic, and mTOR-related proteins. Mimicking the effect of advanced aging, genetic disruption of lysosomal function accelerated the accumulation of storage bodies in AF(+) cells and led to impaired microglia physiology and cell death, suggestive of a mechanistic convergence between aging and lysosomal storage disorders. |
