Montclair Film Festival On Aging

Are Hormetins the new Fountain of Youth in Aging?

Although aging is inevitable—most likely due to the accumulation of damage at the cellular level, rather than from any one specific program—the actual rate of aging can be an adaptive feature in nature. So although we will all die, there is a certain amount of plasticity in how fast we age and therefore how early or late we die. This plasticity is likely to be controlled by relatively simple mechanisms. Aging research focusing on this plasticity has shown some encouraging results.

Hormetins—sometimes referred to as adaptogens—are a mild stress-induced action that has long-term and broad beneficial effects. Following the dictum that what does not kill you make you stronger, hormetins kick start the body to respond to the mild stress and this response has broader and longer-lasting benefits. Benefits that translate to living longer.

Mild Stress can be induced through four main methods. The easiest and most common is physical activity like exercise, heat, gravity and irradiation. There are emerging interest in psychological methods like meditation, brain exercises, juggling and balancing. However, out of all these methods, hormetins—a unit of a hormesis—are best defined by a supplement. Pop a pill and let your body do the work.

Nutritional stress includes caloric restriction, and anti-oxidants, polyphenols—found more commonly in as fruit and vegetables, tea, red wine, coffee, chocolate, olives, and extra virgin olive oil—flavonoids—plants especially parsley, onions, berries, tea, bananas, all citrus fruits, red wine, and dark chocolate—and lastly micronutrients—that include some vitamins and trace amounts of  iron, cobalt, chromium, copper, iodine, manganese, selenium, zinc and molybdenum..

The trick is to ensure that the trauma is mild enough not to be counterproductive.  With nutrients this is easier to achieve since most of these nutritional supplements are water-soluble and therefore in cases of ineffectiveness you are at worst producing expensive urine.

The problem with nutrients is that everyone is trying to make a buck. Not just snake-oil salesman but also academicians and researchers getting into the “business” of selling immortality and anti-aging pills. In table 2 are a number of nutrients on the far right and far left, that are promoted as beneficial to living longer. On the far right, from Rhodioia  down to Glucosamine, these are said to contribute to the mechanism to their left (shaded smaller cirlces), from Stress Resilience to Tumor Suppression.

We can see that although there are many potential mechanisms, in this review there are nine mechanisms they all contribute to the two main and connected mechanisms through their anti-oxidant benefits and by mimicking caloric restriction (large shaded circles to the left).

Hormesis represents a gyroscope in maintaining a balance between an individual and the environment. Even if a slight elevation of a certain toxic chemical, event or condition in the environment occurs, the body chemistry changes to prepare for it. But this balancing act is not without limitation. The capacity for the body to make biological/chemical adjustments is limited, but there is plasticity in this system of person–environment interaction. Nadine Saul with the Humboldt-University of Berlin and his colleagues have argued that the process of hormesis is a balance that has both positive and negative outcomes. It emerged that for every longevity improvement, there is a reduction in the capacity of the organism for growth, mobility, stress resistance, or reproduction. Saul argues (correctly it seems) that longevity comes at a price, and although hormesis seems to promote longevity, other hormetic costs may ensue, some of which are unknown and unpredictable.

The mechanism of hormesis remains an enigma, although we continue to learn more about how the body develops resilience in response to changes in the environment. In 1962, Italian geneticist Ferruccio Ritossa discovered that heat shock proteins are produced when cells are exposed to a variety of stresses. Initially identified with fruit flies that were exposed to a burst of heat resulting in the production of new proteins that help cells survive. The epigenes responsible for this are called “vitagenes” and maintain balance within cells under stressful conditions. As with the heat shock proteins, these act as chaperones, as minders, in assisting the establishment of “proper protein behavior.” Despite these terms, we do not know how this function is carried out.

Similarly, we now acknowledge that caloric restriction itself might be effective because of its hermetic qualities—a shock to the body—rather than through diet. This might be the case since there are  multiple ways of producing the same effect without adhering to a diet of calorie reduction. The underlying mechanism—rather than the reduction of calories—becomes important. And the underlying mechanism is a shock. If we accept this mechanism, then we should ask “why?”   Why does a shock cause the body to build resilience?

The answer is both simple and radical. A shock causes the body to build resilience because the body is designed to do exactly that. Our body interacts with the environment in order to survive. And to accomplish this adaptation there must be plasticity, some wiggle room, in our capacity. And our biology is a constellation of different entities that depend on each other. How it does this adaptation is more enigmatic, but we now know that there are plasmids and bacteria that help address the needs of our body. These might even recombine with our own DNA to make these adaptations more permanent.

Just as Thales of Miletus (624-546 BCE) the ancient Greek philosopher created science by arguing that we should stop referring to natural phenomena as the “will of god,” in our world we should move away from looking at end of life diseases as “caused by aging” and become more appreciative of the balance we maintain with our natural world. By discarding the new mythology of aging—immortality gurus—we can then focus on plasticity in older age. The fountain of youth might be a fountain for living-well in older ages.

© USA Copyrighted 2017 Mario D. Garrett 

References

Garrett, M. (2017). Immortality: With a Lifetime Guarantee. Createspace. USA.

Lenart, P., & Bienertová-Vašků, J. (2017). Keeping up with the Red Queen: the pace of aging as an adaptation. Biogerontology, 18(4), 693-709.

Rattan, S. I. (2017). Hormetins as Drugs for Healthy Aging. In Anti-aging Drugs (pp. 170-180). Royal Society of Chemistry.