Key Points:
- Combining oxytocin with the anti-inflammatory extends the median lifespan of old mice by 14%.
- Oxytocin combined with the anti-inflammatory improves the endurance, agility, grip strength, and memory of old mice.
- The combo suppresses inflammation in old mice.
The concentrations of multiple molecules within our body become altered with age. These alterations include a decline in the “love” hormone oxytocin (OT) and an elevation in a signaling protein called TGF-β. To address these particular alterations, UC Berkeley scientists administered OT and an Alk5 inhibitor (A5i) that inhibits TGF-β to mice. Impressively, as published in Aging, this combo prolonged the lifespan of male mice.
More specifically, OT+A5i extended the median lifespan (0.5 probability of survival, as shown in the image above) of male mice by 14% if counting from birth. However, OT+A5i treatment was administered when the mice were 25-month-old, roughly equivalent to 70-year-old humans. Therefore, if counting from 25 months of age, the combo increased the remaining lifespan of male mice by 73.73%. Unfortunately, for unknown reasons, the therapeutic combo did not extend the lifespan of female mice.
Oxytocin + A5i Extends Healthspan
Healthspan is a term used by geroscientists to describe the duration of life spent in good health. Ideally, an increase in lifespan accompanies an increase in healthspan, as, for example, living to the age of 100 may only be desirable if cognitively lucid and physically fit. Thus, the Berkeley researchers assessed the physical and mental health of mice treated with OT+A5i.
The results showed that, compared to untreated mice, OT+A5i-treated mice ran longer (on the front portion of a small treadmill), suggesting improved endurance. The OT+A5i-treated mice were also able to hang upside down (on mesh wiring) for a longer duration, suggesting improved grip strength, coordination, balance, and agility. Moreover, the treated mice explored novel objects more than objects they were habituated to, suggesting improved short-term memory. Since this did not occur in females, these findings demonstrate that oxytocin + A5i improves the healthspan of male mice.
Oxytocin + A5i Suppresses Inflammation
To obtain an idea of how OT+A5i prolongs lifespan and healthspan, the researchers examined changes in protein levels. After four months of OT+A5i treatment, it was found that high levels of pro-inflammatory proteins decreased in male but not female mice. These findings suggest that a reduction in inflammation contributes to the lifespan and healthspan benefits of OT+A5i in male but not female mice.
Finding an Alk5 inhibitor
While oxytocin supplements are readily available, usually in the form of a nasal spray, Alk5 inhibitors may be more difficult to come by. An Alk5 inhibitor known as vactosertib was shown to be safe in a clinical trial, but has yet to be approved by the Food and Drug Administration (FDA). A possible alternative to vactosertib could be ginseng, which has been shown to inhibit TGF-β and MM9. However, naturally occurring Alk5 inhibitors like ginseng may be less potent than a drug like vactosertib.
Still, oxytocin and Alk5 inhibition were not tested separately, so it is difficult to ascertain the contribution of each compound to the extension of lifespan and healthspan. Each compound on its own has been shown to reap healthspan but not lifespan benefits. Therefore, there may be a possible synergetic effect on lifespan when combining oxytocin with Alk5 inhibition. While speculative, this could mean that supplementation with oxytocin and ginseng could act synergistically.
Combining Longevity Interventions for Better Results
If anything, the study points to the utility of combining longevity interventions, like oxytocin and Alk5 inhibitors, for a more comprehensive and complete therapy. Due to the complex multifactorial nature of aging, a single intervention may not suffice in restoring cellular health. Supporting this idea, a recent study showed that combining two FDA-approved drugs (rapamycin with trametinib) extended the lifespan of mice.
Even so, covering the multitude of age-related alterations with just two compounds is difficult. This is why nutraceutials like Restorin contain multiple longevity interventions designed to target the most important age-related alterations, including senescent cells, chronic inflammation, and mitochondrial dysfunction. In the field of geroscience, where scientists are continuously identifying compounds that slow aging, multi-interventions like Restorin are likely to become the most effective treatment methods.
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