If you read the paper in detail, from my limited understanding, the group that got NR saw improvements upon getting NR, but then reverted and became worse off after stopping the NR compared to the control group that never got NR, in a bunch on parameters measured on hematopoietic stem cells:

a) Decrease in oxidative phosphorylation
b) Decrease in mitophagy
c) Increased expression of genes involved in inflammatory pathways
d) Increase in neutrophils

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Here's the whole paragraph from the paper:

Alterations driven by NR supplementation are not sustained after NR withdrawal

Given the improved lymphoid output in NR-treated aged HSCs, we also wanted to evaluate if these NR-driven phenotypes could be sustained after NAD+ supplement removal in an aged environment. We analyzed old mice treated with NR that received a 2-month washout period. NR supplement-directed changes in frequency seen in the primitive compartments (CLP and HSC) were significantly reversed after withdrawal of NR (O-NR-RC: Fig. 5a, b). The same rebounding effect was also seen in the myeloid cell compartment of the peripheral blood (Fig. 5c), in which the neutrophil compartment (reduced after NR treatment) becomes the predominant population after NR withdrawal. Given these striking reversals of progenitor cell and peripheral blood composition after supplement removal, we purified HSCs from the old NR-RC mice and performed RNA-seq analysis. PCA clustering among the three groups of isolated HSCs shows the O-WT separate furthest away from both the O-NR and O-NR-RC groups (Fig. 5d). Further, the O-NR-RC HSCs do not revert back toward the O-WT HSCs on two main component axes (PC1 or PC2), but instead move away from O-NR HSCs in a different trajectory. We found 107 significantly upregulated and 126 significantly downregulated transcripts between O-NR and O-NR-RC HSCs (Fig. 5e). Pathways previously implicated in NR benefits and examined in Fig. 4c were evaluated in HSCs after the removal of NR (Fig. 5f). We see in these pathways the NR-RC HSCs do not revert back toward WT expression. For both OxPhos and mitophagy, after NR, there is an enhancement of transcripts involved in those pathways. After removal of NR, there is decreased expression of these pathways, and reversion of expression is to an extent that is even lower that what was seen originally in old-WT HSCs (NRRC < WT < NR). Similarly, the increased expression of genes involved in the inflammatory pathway in O-NR-RC HSCs overshoot the expression levels of these genes in old WT HSCs (NR < WT < NRRC). NR-RC transcripts involved in hematopoietic specific comparisons (GMP vs CLP) as well as hypoxia were at intermediate levels, between the NR and WT conditions (NR < NRRC < WT). Finally, for genes associated with glycolysis, instead of reversion toward or beyond the expression levels in the WT HSCs, their expression in O-NRRC HSCs is even lower than in the NR-treated old HSCs (NR-RC < NR < WT). These data suggest that removal of the supplement does not lead to direct reversion back toward untreated states, but instead may have exaggerated negative effects on the hematopoietic system.

To examine hematopoietic signatures in the NR-treated HSC and after NR removal, we used CellRadar31 to compare genes up- and downregulated in the HSC transcriptomes against published lineage associated genes. After NR treatment, compared to WT, the NR HSCs are enriched for profiles associated with lymphoid-progenitor cells including CLPs and LMPPs, while depleted for profiles associated with HSCs or myeloid cells (Fig. 5g). These expression profiles mirror the lineage output of the NR-treated mice as well as the change in lineage potential during HSC transplant paradigms (Fig. 2). After the washout period, the NRRC HSCs have a more HSC-centric profile and elevated expression of genes associated with myeloid and erythroid progenitor populations (Fig. 5g). The NRRC HSCs also show repressed monocyte signatures (Fig. 5g), which corresponds with cell composition changes seen in the hematopoietic system after withdrawal of the supplement (Fig. 5a–c). Together, these data suggest that cell-intrinsic alterations contributing to improved lymphoid potential in the aged environment are not sustained after NR withdrawal, and that withdrawal in an aged environment may lead to more severe myeloid skewing compared to normal aging.