Nutraceutical intervention reverses the negative effects of blood from aged rats on stem cells

Abstract

Aging is associated with a decline in function in many of the stem cell niches of the body. An emerging body of literature suggests that one of the reasons for this decline in function is due to cell non-autonomous influences on the niche from the body. For example, studies using the technique of parabiosis have demonstrated a negative influence of blood from aged mice on muscle satellite cells and neurogenesis in young mice. We examined if we could reverse this effect of aged serum on stem cell proliferation by treating aged rats with NT-020, a dietary supplement containing blueberry, green tea, vitamin D3, and carnosine that has been shown to increase neurogenesis in aged rats. Young and aged rats were administered either control NIH-31 diet or one supplemented with NT-020 for 28 days, and serum was collected upon euthanasia. The serum was used in cultures of both rat hippocampal neural progenitor cells (NPCs) and rat bone marrow-derived mesenchymal stem cells (MSCs). Serum from aged rats significantly reduced cell proliferation as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2'-deoxyuridine (BrdU) assays in both NPCs and MSCs. Serum from aged rats treated with NT-020 was not different from serum from young rats. Therefore, NT-020 rescued the effect of serum from aged rats to reduce stem cell proliferation.

Keywords: Aging; NT-020; Proliferation; Stem cells.

Fig. 1

a Treatment of NPCs with old rat serum (ORS, N = 5) reduces relative cell proliferation as measured by mitochondrial MTT when compared with young rat serum (YRS, N = 5), whereas the serum from old rats treated with NT-020 (ORS-NT, N = 5) is significantly higher than that found with old rat serum (one-way ANOVA F(2,12) = 65.45 followed by Sidak’s multiple comparison test *p < 0.05; **p < 0.001). A similar effect is observed in (b) when examining BrdU-positive cells after 48-h treatment with 10 % serum. There is a significant negative effect of old rat serum on the number of BrdU-positive cells, and this is increased in NPCs treated with serum from old rats fed NT-020 (one-way ANOVA F(2,17) = 13.64, followed by Sidak’s multiple comparison test ***p < 0.001; *p < 0.05)

Fig. 2

a Bar graphs demonstrating that treatment of aged rats with NT-020, but not young rats, significantly increased the relative cellular proliferation in MSCs treated with serum from these rats (one-way ANOVA F(3,16) = 8.746 followed by Sidak’s multiple comparison test **=p < 0.01). b It can be observed that old rat serum decreases proliferation of MSCs when compared with young serum when measured using BrdU. Serum from aged rats treated with NT-020 increased the proliferation of MSCs when compared with serum from aged controls (one-way ANOVA F(3,12) = 11.22 followed by Sidak’s multiple comparison ***p < 0.001; *p < 0.05)