Table 3.
Proposed therapeutic approaches for the rejuvenation of senescent microglia.
| Approaches | Effects |
|---|---|
| ANTI-INFLAMMATORY AND ANTIOXIDANT APPROACHES | |
| Minocycline | Inhibits microglial activation, decreases microglial proinflammatory cytokine production |
| IL1RA | Inhibits IL1β-mediated proinflammatory signaling |
| Dietary supplementation with antioxidants: flavonoids (e.g., luteolin, quercetin, genistein, hesperetin), retinoids/carotenoids (e.g., astaxanthin, crocin, crocetin, retinoic acid, lutein, zeaxanthin), vitamins (E and D3) | Exerts antioxidant and anti-inflammatory effects, decreases markers of neuroinflammation |
| PREVENTING OR REVERSING MICROGLIAL “RUN-DOWN” IN AGING | |
| Decreasing lipofuscin accumulation with visual cycle modulators (ACU-4429, fenretinide) | Partially inhibits the visual cycle to decrease ocular lipofuscin formation in retinal microglia |
| Stimulation of microglial autophagy (e.g., anti-lipolytic drugs, rapamycin) | Increases autophagy to promote mitochondria turnover in microglia |
| Stimulation of TFAM expression or activity (e.g., resveratrol, brimonidine) | Inhibits accumulation of mtDNA mutations in microglial mitochondria, decreasing ROS production |
| MODULATION OF THE AGING MICROGLIAL MILIEU | |
| Stimulation of CX3CL1-CX3CR1 signaling | Decreases microglial activation states |
| Stimulation of CD200-CD200R signaling [stimulation of IL4 signaling, fibroblast growth loop (FGL)] | Decreases microglial activation states |
| Exercise | Decreases microglial activation states, up-regulates proliferation of neural precursor cells |
| REPLACEMENT OF AGED MICROGLIA | |
| Depletion, followed by autologous or exogenous repletion by bone marrow derived cells | Enables the replacement of endogenous aged microglia with “replacement” immune cells that can carry out microglial functions |
| Cell-based therapies involving stem cells | Enables the replacement of endogenous aged microglia with “replacement” immune cells that can carry out microglial functions |