Study summary · research use only
AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this in vitro study using human adipose-derived mesenchymal stromal cells (MSCs) cultured to passage (P) 5, cells were grown in normal medium (control), medium with AICAR (1 mM) and nicotinamide (NAM, 5 mM), or both, for 5 weeks to P10, with proliferation, differentiation, apoptosis, autophagy, morphology, and mTORC1/AMPK activity compared among groups. AICAR, NAM, or both were associated with increased proliferation and osteogenic differentiation, greatest with both combined, plus decreased β-galactosidase expression and younger morphologic features. NAM was associated with reduced total cellular ROS in aged MSCs while AICAR was not, and AICAR-treated cells showed the highest proliferation capacity but also the highest apoptosis. The authors describe co-administration as showing an additive or synergistic effect on cellular senescence.
Abstract
Mesenchymal stromal cell (MSC) stemness capacity diminishes over prolonged in vitro culture, which negatively affects their application in regenerative medicine. To slow down the senescence of MSCs, here, we have evaluated the in vitro effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, and nicotinamide (NAM), an activator of sirtuin1 (SIRT1). Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10. Cell proliferation, differentiation capacity, level of apoptosis and autophagy, morphological changes, total cellular reactive oxygen species (ROS), and activity of mTORC1 and AMPK were compared among different treatment groups. MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both. Treatment with AICAR or NAM led to decreased expression of β-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs. Furthermore, while NAM administration could significantly reduce the total cellular ROS in aged MSCs, AICAR treatment did not. Moreover, AICAR-treated cells possess a high proliferation capacity; however, they also show the highest level of cellular apoptosis. The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy. Selective inhibition of mTORC1 by AICAR and NAM boosts autophagy, retains MSCs' self-renewal and multi-lineage differentiation capacity, and postpones senescence-associated changes after prolonged in vitro culture. Additionally, co-administration of AICAR and NAM shows an additive or probably a synergistic effect on cellular senescence.
pepmg summarizes the peer-reviewed literature and links to every source — it sells nothing, ships nothing, and gives no medical, dosing, or human-use guidance. Don't just trust this summary: follow the citation to its source and read it yourself. Research use only.