Abstract
Single-ingredient dietary supplements have demonstrated some potential to extend lifespan and improve healthspan; however, the efficacy of defined multi-ingredient nutraceuticals remains underexplored. Senolytic interventions have been successful in reducing multi-morbidity, frailty, and cognitive decline in animal models and are seen as promising anti-ageing interventions in mammals. We compared the effects of a 12-ingredient nutraceutical on mice lifespan and healthspan markers with that of a high efficacy senolytic intervention consisting of a low dose of Navitoclax combined with the specific mitochondrial uncoupler BAM15. Both interventions were started at old age (20 months). The supplement was given daily until the end of the experiment (30 months of age), but the senolytic intervention consisted of two short (5 days each) rounds of treatment at 20 and 23 months of age. Despite late onset, both interventions increased median lifespan similarly by around 20% over controls. The senolytic intervention significantly reduced frailty progression and improved cognitive function after the second round of treatment, but without subsequent treatment, these effects appeared to wane at later ages. The multi-ingredient supplement tended to reduce frailty progression steadily with time, albeit not significant, and maintained cognitive function. Mechanistically, in vitro, there was no evidence of senolytic activity of the multi-ingredient nutraceutical as a whole nor of its individual ingredients. Continuous multi-ingredient dietary supplementation shows promise in achieving comparable anti-ageing efficacy as a senolytic intervention.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Typos have been corrected: In Results, “C57BL/6J” to “C57Bl/6J”; “(Median survival increased .....) from 703 [637,714] days in controls to 830 [670,864] days in the DS group and to 850 [645,889] days in the SEN group.” to “from 703 [637,720] days in controls to 830 [645,868] days in the DS group and to 834 [637,889] days in the SEN group.”; in ‘Discussion’, “There was evidence of senolytic activity of the NOVOS multi-ingredient supplement or its individual ingredients in human fibroblasts.” to “There was no evidence of senolytic activity of the NOVOS multi-ingredient supplement or its individual ingredients in human fibroblasts.”
