A new Geroscience paper reports that nicotinamide riboside (NR) supplementation can partially reverse microglial aging and improve cognitive performance in old male mice, reinforcing the idea that NAD⁺ restoration is a credible lever for protecting the aging brain. In 22-month-old mice—roughly equivalent to late-life humans—eight weeks of NR (400 mg/kg/day) restored NAD⁺/NADH balance, reduced glial activation, and shifted microglial gene expression away from inflammatory, chemokine-rich states toward a younger, homeostatic phenotype. The transcriptomic data are consistent with a microglial “reset”: inflammatory genes were broadly suppressed, while genes supporting learning, memory, and gliogenesis were upregulated.
These molecular changes translated into better performance on memory tasks. NR-treated mice retained nest-building capacity, performed better in Y-maze assessments of working memory, and showed stronger recognition memory. Importantly, NR also reduced expression of lipoprotein lipase, a marker of “disease-associated microglia,” and attenuated age-related increases in microglial fatty-acid metabolism—one of the signatures believed to drive maladaptive neuroinflammation with age.
Actionable Insights for Longevity-Oriented Biohackers
The study strengthens several practical directions that serious longevity biohackers already explore:
1. NAD⁺ precursor supplementation remains one of the more defensible brain-aging interventions.
NR and NMN both raise NAD⁺, though NR has more direct data in mammalian brain tissue. This study reinforces its potential for microglial homeostasis—an upstream determinant of cognitive aging. Individuals using NR typically employ doses in the 300–600 mg/day range; the murine dose used here is not directly translatable but supports the mechanistic rationale for human experimentation.
2. Stack NR with lifestyle practices that independently raise NAD⁺.
Exercise, time-restricted feeding, and cold exposure all boost NAD⁺ turnover and AMPK-SIRT1 signaling. Stacking NR with these behaviors may have additive effects on mitochondrial maintenance and inflammatory tone.
3. Target microglial inflammation through parallel mechanisms.
Compounds with evidence for microglial modulation—such as low-dose lithium, EPA-rich omega-3s, spermidine, and caloric restriction mimetics—may synergize with NAD⁺ precursors. The present study highlights fatty-acid metabolism in microglia as a distinct node; interventions that reduce lipotoxicity (omega-3s, metabolic flexibility training, improved insulin sensitivity) plausibly complement NR.
4. Cognitive tracking should accompany any self-experimentation.
Because behavioral improvements were central to this study, biohackers should pair NAD⁺ precursor use with objective measures: dual-n-back, CANTAB-style assessments, sleep-quality metrics, and HRV-based inflammation proxies.
Limitations
All data come from aged male mice; microglial aging is sexually dimorphic in rodents and humans. The intervention was short relative to lifespan, and murine cognition only approximates human cognitive domains. NR corrected only part of the age-related transcriptomic drift, indicating partial rejuvenation, not full reversal.
Still, the study sharpens the mechanistic link between NAD⁺ depletion, microglial dysfunction, and cognitive aging—and offers credible, testable strategies that longevity-focused individuals can incorporate while awaiting human trial data.
Source Paper (Open Access): Nicotinamide riboside supplementation restores microglial health and improves cognition in aged male mice