Non-linear actions of physiological agents: Finite disarrangements elicit fitness benefits

Abstract

Finite disarrangements of important (vital) physiological agents and nutrients can induce plethora of beneficial effects, exceeding mere attenuation of the specific stress. Such response to disrupted homeostasis appears to be universally conserved among species. The underlying mechanism of improved fitness and longevity, when physiological agents act outside their normal range is similar to hormesis, a phenomenon whereby toxins elicit beneficial effects at low doses. Due to similarity with such non-linear response to toxins described with J-shaped curve, we have coined a new term “mirror J-shaped curves” for non-linear response to finite disarrangement of physiological agents. Examples from the clinical trials and basic research are provided, along with the unifying mechanisms that tie classical non-linear response to toxins with the non-linear response to physiological agents (glucose, oxygen, osmolarity, thermal energy, calcium, body mass, calorie intake and exercise). Reactive oxygen species and cytosolic calcium seem to be common triggers of signaling pathways that result in these beneficial effects. Awareness of such phenomena and exploring underlying mechanisms can help physicians in their everyday practice. It can also benefit researchers when designing studies and interpreting growing number of scientific data showing non-linear responses to physiological agents.

Balance between Health Risks and Benefits for Outdoor Workers Exposed to Solar Radiation: An Overview on the Role of Near Infrared Radiation Alone and in Combination with Other Solar Spectral Bands

“…The phenomenon by which an agent is stimulatory (then potentially beneficial) at low doses and hazardous at higher doses is known as "hormesis" or "adaptive response." Hormesis was shown to occur at all levels of the biological organization (cell, tissue or the whole body), for a variety of effects, both acute or long-lasting (including carcinogenesis), as well as in relation to physiological agents (see for instance [40][41][42]). The adaptive response may result in increased resilience of tissues and the whole body to environmental and physiological stresses.…”

Phoenix dactylifera L. Pollen and Fluvoxamine Maleate Protect PC12 Cells Against H2O2-Induced Oxidative Stress by Involvement of Nrf2 and SIGMAR1 Gene Expression

“…According to findings, H2O2 below 100 µM is nontoxic. Previous studies have demonstrated that H2O2 can inhibit cell growth and cause cell death; higher doses of H2O2 can lead to oxidative stress (24). In this study, 100 µM H2O2 induced oxidative stress with less severe apoptotic effects.…”

Heart failure in patients is associated with downregulation of mitochondrial quality control genes

“…11,39 Such dichotomy in the effects of UPRmt elements on heart could be a result of a non-linear response, whereby a moderate activation of UPRmt protects cardiomyocytes, while its excessive activity becomes harmful. 1,40 UPRmt protease YME1L reduces mitochondrial protein import by inactivating TIM17A, which is a mechanism downstream of eIF2α activation. 8 Our results demonstrate downregulation of most of tested elements of TIM23 and TIM22 translocons in ICM and DCM, which could in patients with HF prevent overload of mitochondria with proteins in a situation when UPRmt activity is reduced.…”

“…Similarly, upregulation of LONP1 and OMI caused HF 11,39 . Such dichotomy in the effects of UPRmt elements on heart could be a result of a non‐linear response, whereby a moderate activation of UPRmt protects cardiomyocytes, while its excessive activity becomes harmful 1,40 …”