Nonlinear Stimulation and Hormesis in Human Aging: Practical Examples and Action Mechanisms

Abstract

The process of aging is accompanied by a progressive reduction of biological dynamical sophistication, resulting in an increased probability of dysfunction, illness, and death. This loss of sophistication is inherent in all aging organisms. However, it may be possible to retard the rate of loss of biological complexity by introducing an increased amount of nonlinear, nonmonotonic external stimulation that challenges the organism and forces it to upregulate its biological processes. This can be achieved by exploiting the multiple effects of hormesis, through a wide range of challenges including physical, mental, and biological stress. Hormesis is widely encountered in biological systems, and its effects are also seen in humans. It is possible to use hormetic strategies (both conditioning hormesis and postexposure conditioning hormesis) to enhance the function of repair processes in aging humans and therefore prevent age-related chronic degenerative diseases and prolong healthy lifespan. Such techniques include dietary restriction and calorie restriction mimetics, intermittent fasting, environmental enrichment, cognitive and sense stimulation, sexuality-enhancing strategies, exposure to low or to high temperatures, and other physicochemical challenges. Current research supports the general principle that any type of a hormetic dose-response phenomenon has an effect that does not depend on the type of stressor and that it can affect any biological model. Therefore, novel types of innovative, mild, repeated stress or stimulation that challenge a biological system in a dose-response manner are likely to have an effect that, properly harnessed, can be used to delay, prevent, or reverse age-related changes in humans.

Pathways of Prevention: A Scoping Review of Dietary and Exercise Interventions for Neurocognition

“…Hormesis reflects the adaptive response of the brain to intermittent, low-dose environmental exposures (e.g. dietary energy restriction) that enhance systemic functional response capabilities [97,98]. More recent evidence suggests that alterations in phospholipid metabolism may be particularly important to the progression of subclinical ADRD biomarkers of cortical atrophy [99].…”

Psychoneuroendocrine immunology (PNEI) and longevity

“…Other forms of hormesis and PNEI interaction regard the possibility to have mental and social stimulation through environmental enrichment, social and spiritual activities, technology (i.e. internet) which are able to act in a hormetic fashion on the PNEI components: a possible positive stimulation has been emphasized by Kyriazis within this field [80] .…”

Cybernetic Principles of Aging and Rejuvenation: The Buffering- Challenging Strategy for Life Extension

“…Such a hormetic effect of physical stress has recently been promoted as an anti-aging strategy by several authors (Gems & Partridge, 2008;Kyriazis, 2010;Rattan, 2008). However, the original definition of hormesis (Calabrese & Baldwin, 2002) is a dose-dependent effect of stressors: initially, for small amounts, the effect is positive, but as the dose increases, the effect becomes increasingly negative.…”

“…This ensures both that we accumulate a wide range of protective, buffering nutrients, such as antioxidants, and that we get exposed to a wide variety of toxins to challenge the organism's detoxification capabilities. Several authors suggest that the disease-preventing and lifeextending effects of many vegetables, such as those from the cabbage family, and spices, such as turmeric and pepper, are actually due to the hormetic effect of the toxins they contain in order to ward off predation (Kyriazis, 2010;Rattan, 2008).…”

“…While this general, "cybernetic" approach towards life extension and rejuvenation is new, most of its components have already been proposed and investigated by different authors, in particular from the "paleo" (De Vany, 2010;Durant, 2013;Sisson, 2009) and "hormetic" (Gems & Partridge, 2008;Kyriazis, 2010;Rattan, 2008) producing an overall benefit that is more than the sum of its parts. This can be understood by examining the positive feedback involved in aging.…”