Interspecies Chemical Signals Released into the Environment may Create Xenohormetic, Hormetic and Cytostatic Selective Forces that Drive the Ecosystemic Evolution of Longevity Regulation Mechanisms

Abstract

Various organisms (i.e., bacteria, fungi, plants and animals) within an ecosystem can synthesize and release into the environment certain longevity-extending small molecules. Here we hypothesize that these interspecies chemical signals can create xenohormetic, hormetic and cytostatic selective forces driving the ecosystemic evolution of longevity regulation mechanisms. In our hypothesis, following their release into the environment by one species of the organisms composing an ecosystem, such small molecules can activate anti-aging processes and/or inhibit pro-aging processes in other species within the ecosystem. The organisms that possess the most effective (as compared to their counterparts of the same species) mechanisms for sensing the chemical signals produced and released by other species and for responding to such signals by undergoing certain hormetic and/or cytostatic life-extending changes to their metabolism and physiology are expected to live longer then their counterparts within the ecosystem. Thus, the ability of a species of the organisms composing an ecosystem to undergo life-extending metabolic or physiological changes in response to hormetic or cytostatic chemical compounds released to the ecosystem by other species: 1) increases its chances of survival; 2) creates selective forces aimed at maintaining such ability; and 3) enables the evolution of longevity regulation mechanisms.

Empirical Validation of a Hypothesis of the Hormetic Selective Forces Driving the Evolution of Longevity Regulation Mechanisms

“…One of the key aspects of our hypothesis of the hormetic selective forces driving the evolution of longevity regulation mechanisms is an assumption that all yeast species within an ecosystem can respond to LCA and other bile acids released into the ecosystem by animals (Goldberg et al, 2010a,b; Burstein et al, 2012a). This response consists in the ability of yeast to develop mechanisms of protection against cellular damage caused by the mildly toxic molecules of bile acids (Goldberg et al, 2010a,b; Burstein et al, 2012a).…”

“…This response consists in the ability of yeast to develop mechanisms of protection against cellular damage caused by the mildly toxic molecules of bile acids (Goldberg et al, 2010a,b; Burstein et al, 2012a). Of note, our analysis of how different concentrations of LCA impact yeast longevity has revealed that this bile acid delays yeast chronological aging by eliciting a hormetic stress response (Goldberg et al, 2010b; Burstein et al, 2012a), which is characterized by a non-linear and biphasic dose–response curve (Goldberg et al, 2010a; Calabrese and Mattson, 2011; Burstein et al, 2012a; Calabrese et al, 2012; Leonov et al, 2015; Lutchman et al, 2016).…”

“…Bile acids extend healthy lifespan in animals also because they act as signaling molecules that enable to sustain lipid, glucose, and energy homeostasis (Motola et al, 2006; Gerisch et al, 2007; Russell and Kahn, 2007; Ramalho et al, 2008; Thomas et al, 2008; Amaral et al, 2009; Hylemon et al, 2009; Lefebvre et al, 2009; Monte et al, 2009; Tiwari and Maiti, 2009; Vallim and Edwards, 2009; Goldberg et al, 2011, 2013; Pols et al, 2011; Wollam et al, 2011, 2012; Lee and Schroeder, 2012; Chiang, 2013; de Aguiar Vallim et al, 2013; Groen and Kuipers, 2013; Li and Chiang, 2013; Magner et al, 2013; Arlia-Ciommo et al, 2014b; Mahanti et al, 2014). Moreover, bile acids extend healthy lifespan in animals because these mildly toxic molecules with detergent-like properties can activate detoxification of xenobiotics, thus promoting chemical hormesis and operating as endobiotic regulators of aging that improve health and prolong longevity (Amador-Noguez et al, 2004, 2007; Gems, 2007; Russell and Kahn, 2007; Gems and Partridge, 2008; Burstein et al, 2012a; Arlia-Ciommo et al, 2014b; Li and Chiang, 2014; Medkour and Titorenko, 2016). …”

“…We therefore hypothesized that bile acids released into the environment by animals composing an ecosystem may act as interspecies chemical signals that create selective pressure for the evolution of longevity regulation mechanisms in yeast within this ecosystem (Goldberg et al, 2010a; Burstein et al, 2012a). Our hypothesis posits the following: (1) only yeast exposed to exogenous bile acids can develop mechanisms of protection against cellular damage caused by these external stress agents and hormetic stimuli; (2) some of these mechanisms developed against bile acid-induced cellular damage can also protect yeast against damage and stress accumulated purely with age; (3) only those yeast species that have developed (due to exposure to exogenous bile acids) the most protective mechanisms against bile acid-induced cellular damage can also develop protective mechanisms against damage and stress accumulated with age; and (4) these yeast species are therefore expected to live longer (Goldberg et al, 2010a,b; Burstein et al, 2012a). In this hypothesis, the presence of exogenous bile acids creates hormetic selective force that drives the evolution of not only protective mechanisms against bile acid-induced cellular damage but also longevity regulation mechanisms that protect against damage and stress accumulated with age.…”

“…In this hypothesis, the presence of exogenous bile acids creates hormetic selective force that drives the evolution of not only protective mechanisms against bile acid-induced cellular damage but also longevity regulation mechanisms that protect against damage and stress accumulated with age. Moreover, this hypothesis suggests that yeast cells that are not exposed to exogenous bile acids cannot develop mechanisms of protection against cellular damage caused by these mildly toxic molecules (Goldberg et al, 2010a,b; Burstein et al, 2012a). Thus, these yeast cells are unable to develop mechanisms of protection against damage and stress accumulated purely with age.…”