During my previous post I mentioned how the evolutionary theory of aging was tested empirically by selective breeding of fruit flies for longevity and later on for shorter lifespans.
The longer lived fruit flies obtained in the lab got the nickname of Methuselah flies. Displaying a longer mean and maximum lifespan, they expressed hundreds of genes differently compared to shorter-lived fruit flies. They also had better resistance to stress.
If aging happens because the force of natural selection diminishes with age as fewer individuals contribute to the next generation’s gene pool then a logical conclusion may be that adaptogens or substances that increase the adaptation to one’s environment may function as anti-aging therapies.
And since so many genes are expressed differently between the longer-lived and the short-lived fruit flies – possibly in other species as well – it is highly unlikely that one substance may be enough to delay aging.
Adaptogens are substances which increase the nonspecific stress resistance of an organism. Since they don’t follow the model of “one target, one drug” and many clinical trials were done in the USSR in the 60s and 70s with not much published data according to current good laboratory practice standards, the adaptogenic concept is not yet accepted by the European Medicines Agency. Yet this doesn’t preclude some substances from increasing stress resistance and acting as adaptogens as it happened in experiments published in this paper.
The short story is that 3 groups of Drosophila melanogaster fruit flies were used:
-the control group
-SC100 treated flies
-SC100 treated flies starting on day 36
where SC100 is a dietary supplement containing 4 herbal extracts:
- Astragalus membranaceus root – which activates VEGF and inhibits mTOR in rats
- Pterocarpus marsupium bark – which is a source of resveratrol analogs such as pterostilbene (25% standardized in the used extract), marsupin and pterosupin
- pine bark extract containing oligomeric proanthocyanidins (85% standardized) – the latter activate endothelial nitric oxide synthesis (NOS) and inhibit NF-KappaB
- L-theanine (98% pure) – an amino acid from green tea which crosses the blood-brain barrier and binds to GABA
This cocktail of herbal extracts acted on quite a few of the metabolic pathways involved in aging: mTOR, NOS, NF-KappaB, VEGF. The SC100 treated flies not only lived longer but also displayed increased partial starvation (10% dilution of food) and heat (29 C) stress resistance. If everything else remained constant, my take is that this mix of substances acted as an adaptogen and this is how life extension was achieved.
Compared to controls, treated fruit flies had a 27% increased mean lifespan when they were started on SC100 on day 36 of the longevity assay and 49% when they were treated with it from the beginning.
Control fruit flies were all dead at 60 days.
Lifetime treated fruit flies were all dead at 134 days.
The treated fruit flies who were started on SC100 on day 36 lived almost as much and even in this case, the maximum lifespan achieved by survivors was doubled.
Unlike calorie restriction which also extends lifespan in fruit flies but diminishes fecundity, SC100 increased fertility in older females (of 4 weeks) whereas no difference in fertility existed in younger ones (of 2 weeks).
Yet SC100 did not prolong lifespan significantly if the fruit flies lived in a low stress environment with a normal circadian rhythm, probably because a low stress environment extends lifespan in the control fruit flies as well.
The treatment that was administered to the fruit flies corresponds to a human dose equivalent of 900 mg or 2 capsules per day. I’ve noticed that since publishing the above mentioned paper on fruit flies, the Stem Cell 100® and Stem Cell 100+® dietary supplements contain many more herbal extracts with the latter also containing folate, vitamin B12 and vitamin D3; yet outside a proven deficit in these vitamins, I’d stay away from supplementing with them.
Unlike the large sample sized fruit fly study mentioned above, Stem Cell 100+® was tested on a tiny sample of 15 healthy subjects in an open label pilot study registered here. They took a 650mg capsule twice daily for 15 months and the results were published here and here.
My take on all this is that lifespan can be extended either by reducing stress in the environment or by increasing stress resistance. Most likely it is a combination of both.
For example, very long-lived marine invertebrates live on the bottom of the sea where there is not much variation in environmental parameters like temperature. Increased stress resistance is more widely encountered in long-lived and/or negligibly senescent species as these live in environments with few nutrients, intermittent oxygen and low temperatures.
While many of these adaptations took place by natural selection, such interventions have prolonged lifespans in lab conditions as well. Calorie restriction may act as a mild stressor which increases the stress resistance of the organism thereby making it last longer while lowering the environmental temperature increases lifespan in many invertebrates. Exercise may act in a similar manner to increase lifespan.
Through their systemic effects, pharmacological adaptogens may trigger in a shorter time what evolution is capable of after lots of generations: an increased level of stress resistance at advanced ages and with it delayed aging and longer lifespans. As such, this group of substances could provide a different strategy to slow the rate of aging and postpone the onset of many age-related diseases.
References
Villeponteau, B., Matsagas, K., Nobles, A. C., Rizza, C., Horwitz, M., Benford, G., & Mockett, R. J. (2015). Herbal supplement extends life span under some environmental conditions and boosts stress resistance. PloS one, 10(4), e0119068.
Villeponteau, B. (2018). Multipath Herbal Nutraceutical Improves Self-Reported Markers of Health and Life Expectancy in Clinical Study. SF J Herb Med, 2(1).
Villeponteau, B., & Still, Y. L. (2017). Treating multiple antiaging pathways improves health markers in open label clinical study. Translational Medicine Communications, 2(1), 9.
