Key Points:
- Meclizine extends male mouse lifespan by ~8%.
- Astaxanthin prolongs the lifespan of male mice by ~12%.
- Interestingly, fisetin, a compound known for eliminating aging-related dysfunctional cells (senescent cells), confers no effects on either mouse lifespan or tissue senescence.
A consortium of researchers that test longevity interventions in mice uses a large number of mice to enhance the statistical power of their findings. Moreover, they perform their tests at three different locations — the University of Michigan, the Jackson Laboratory in Maine, and the University of Texas Health Science Center at San Antonio — to assure the replicability and reliability of their results.
In the past, this consortium has only found seven interventions that prolong mouse lifespan. These include the anti-diabetes drugs acarbose and canagliflozin, the antioxidant compounds nordihydroguaiaretic acid and protandim, a weaker form of the sex hormone estrogen called 17-α-estradiol, the immunosuppressant rapamycin, and the anti-inflammatory compound aspirin. More recently, however, researchers from this group have identified two more compounds that can be easily attained over-the-counter.
Published in GeroScience, Richard Miller and colleagues show that the anti-motion sickness drug meclizine and the antioxidant compound astaxanthin moderately extend male mouse median lifespans. Meclizine extends the male mouse median lifespan by ~8%, while astaxanthin prolongs median lifespan by ~12%. Interestingly, these researchers also tested fisetin, a senolytic compound. Senolytics are known to eliminate aging-related dysfunctional cells (senescent cells). Fisetin has been shown in previous studies to extend mouse lifespan, and this study found that it had no such lifespan-extending effects. Furthermore, fisetin did not show evidence of eliminating senescent cells. These findings, deriving from rigorous and meticulous experimentation techniques, suggest that the over-the-counter compounds meclizine and astaxanthin could be candidates for future human trials testing their potential pro-longevity benefits.
Meclizine and Astaxanthin Significantly Extend Male Mouse Lifespan
The new, highly anticipated data showed that meclizine increases male, but not female, median lifespan by ~8%. Miller and colleagues chose to test this antihistamine, anti-nausea, and anti-vertigo drug, because it suppresses the activation of a cell growth-regulating protein complex — mTORC1. Rapamycin, a drug shown to prolong both male and female lifespan also inhibits mTORC1 but has immunosuppressive and red blood cell production inhibiting side effects. Because meclizine suppresses mTORC1 similar to rapamycin but is not known for having rapamycin’s side effects, the researchers found it to be an attractive candidate for lifespan enhancement effects.
The other over-the-counter supplement shown to extend median lifespan in male mice by ~12% was the antioxidant astaxanthin. Interestingly, astaxanthin has a pink or light reddish hue, and it is produced in algae. Trout, krill, shrimp and crayfish that eat astaxanthin-containing algae thus attain a pinkish coloration. Because astaxanthin had been shown to extend lifespan in other animal models such as yeast, worms, and flies, Miller and colleagues chose to test its effects on lifespan in mice.
Interestingly, a plant-derived compound that has been shown to have senolytic effects and extend mouse lifespan in other research, fisetin, did not prolong lifespan in Miller and colleagues’ study. Moreover, the researchers did not find that it reduces a protein marker often used to identify senescent cells — p16 — in the liver, kidney, or brain tissues of mice. These findings suggest that fisetin may not be all that it has been cracked up to be related to eliminating senescent cells and extending mouse lifespan.
“Positive results, like those reported here for [astaxanthin] and [meclizine], are important contributions to the literature, providing new clues about mechanisms of aging and pathways to prevent age-related disease and disability,” say Miller and colleagues. “Ultimately, this will suggest clinical treatments.”
Following Up with Human Trials Testing Meclizine and Astaxanthin
The lifespan extension effects of meclizine and astaxanthin in male mice may pave the way for human trials testing whether these compounds confer pro-longevity benefits. Because of Miller and colleagues’ rigorous testing, their identification of potential lifespan-extending compounds elicits excitement among the aging research community. As such, it seems likely that follow-up research testing the effects of these two compounds on aging will ensue in the next few years.
One caveat is that the lifespan-promoting effects of meclizine and astaxanthin did not occur in females. This is not a new phenomenon in mouse research since numerous molecules tested in mice have greater benefits for one sex compared to the other. For example, rapamycin was shown to have a greater lifespan extension effect in females.
The reasons for these sex differences remain unclear, but there are some clues. In the experiment showing that rapamycin works better in females, females had more rapamycin in their blood. In the same regard, Miller and colleagues showed in this study that males, with longer median lifespans, had higher concentrations of meclizine and astaxanthin in their blood. Since higher doses of a compound usually increase blood levels, the possibility looms that the sex with lower blood concentrations of a given compound requires higher doses to increase their blood levels and for a longevity-related effect to occur.
The results showing that fisetin did not extend mouse lifespan or reduce senescent cells are also intriguing. As research has demonstrated fisetin to be a potent senolytic with potential mouse lifespan-extending effects, Miller and colleagues’ findings derived from rigorous and meticulous testing techniques run counter to prevailing classifications of this molecule. Nonetheless, these researchers were not able to reproducibly detect fisetin in the mice’s blood plasma. Along those lines, using higher doses of fisetin may be necessary for this compound to confer pro-longevity benefits. For this reason, Miller and colleagues’ group may not necessarily stop testing fisetin for longevity-related benefits.
Anyone interested in taking meclizine and/or astaxanthin can easily find and order both compounds online. The long-term effects of ingesting these compounds are not well-understood. Therefore, it is advisable for anyone considering their extended use to consult with a physician beforehand.
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