A View of Aging Centered Around the Capacity for Hormesis

It is not too far from the truth to say that everyone in the field of aging research has their own theory of aging. Enormous amounts of data exists, measurements of near every aspect of cellular biochemistry, to note the ways in which these aspects change with age, yet we lack the framework to link all of the data together, to firmly state what is important and what is not, what is cause, what is consequence, and how exactly the network of age-related changes are linked to one another. Aging is a dark forest in which the boundaries are well mapped, but only a few of the interior features have been well explored.

So why not a view of aging centered around hormesis? That is the topic covered by today's open access commentary. It is similar in many ways to views of aging centered around the capacity for resilience in the face of stress. If a biological system cannot right itself after experiencing some form of perturbation, then the odds of catastrophic failure might be expected to be higher. This, at the core of it, is aging: an increased risk of catastrophic failure resulting from loss of functional capacity. Unfortunately, when it comes to treating aging as a medical condition one can't stop there, and the fine details of the biochemistry involved are in fact of great importance.

Hormesis defines the limits of lifespan

This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of numerous degenerative diseases and debilitating effects of aging. It proposes that the most fundamental, evolutionary-based integrative strategy to sustain and protect health is based on the concept of hormesis. This concept integrates anti-oxidant, anti-inflammatory, and cellular repair responses at all levels of biological organization (i.e., cell, organ and organism) within the framework of biphasic dose responses that describe the quantitative limits of biological plasticity in all cells and organisms from bacteria and plants to humans.

A major feature of the hormetic concept is that low levels of biological, chemical, physical and psychological stress upregulate adaptive responses that not only precondition, repair and restore normal functions to damaged tissues/organs but modestly overcompensate, reducing ongoing background damage, thereby enhancing health beyond that in control groups, lacking the low level "beneficial" stress. Higher doses of such stress often become counterproductive and eventually harmful. Hormesis is active throughout the life-cycle and can be diminished by aging processes affecting the onset and severity of debilitating conditions/diseases, especially in elderly subjects.

The most significant feature of the hormetic dose response is that the limits of biological plasticity for adaptive processes are less than twice that of control group responses, with most, at maximum, being 30-60 % greater than control group values. Yet, these modest increases can make the difference between health or disease and living or dying. The quantitative features of these adaptive hormetic dose responses are also independent of mechanism. These features of the hormetic dose response determine the capacity to which systems can adapt/be protected, the extent to which biological performance (e.g., memory, resistance to injury/disease, wound healing, hair growth, or lifespan) can be enhanced/extended and the extent to which synergistic interactions may occur.

Hormesis defines the quantitative rules within which adaptive processes operate and is central to evolution and biology and should become transformational for experimental concepts and study design strategies, public health practices, and a vast range of therapeutic strategies and interventions.

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