Longevity, cellular senescence and the gut microbiome: lessons to be learned from crocodiles

Abstract

Crocodiles are flourishing large-bodied ectotherms in a world dominated by endotherms. They survived the Cretaceous extinction event, that eradicated the dinosaurs who are thought to be their ancestral hosts. Crocodiles reside in polluted environments; and often inhabit water which contains heavy metals; frequent exposure to radiation; feed on rotten meat and considered as one of the hardy species that has successfully survived on this planet for millions of years. Another capability that crocodiles possess is their longevity. Crocodiles live much longer than similar-sized land mammals, sometimes living up to 100 years. But how do they withstand such harsh conditions that are detrimental to Homo sapiens ? Given the importance of gut microbiome on its' host physiology, we postulate that the crocodile gut microbiome and/or its' metabolites produce substances contributing to their “hardiness” and longevity. Thus, we accomplished literature search in PubMed, Web of Science and Google Scholar and herein, we discuss the composition of the crocodile gut microbiome, longevity and cellular senescence in crocodiles, their resistance to infectious diseases and cancer, and our current knowledge of the genome and epigenome of these remarkable species. Furthermore, preliminary studies that demonstrate the remarkable properties of crocodile gut microbial flora are discussed. Given the profound role of the gut microbiome in the health of its' host, it is likely that the crocodile gut microbiome and its’ metabolites may be contributing to their extended life expectancy and elucidating the underlying mechanisms and properties of these metabolites may hold clues to developing new treatments for age-related diseases for the benefit of Homo sapiens .

Novel Sources of Bioactive Molecules: Gut Microbiome of Species Routinely Exposed to Microorganisms

“…Consequently, these microorganisms should also be recovered and the activities of their metabolites should be determined. Recent analyses of crocodilian genomes showed that these have evolved very slowly over the past several million years, and it would be useful to understand how these slow-evolving species are able to thrive over millions of years, despite ongoing environmental changes [ 86 ]. Alternatively or concurrently, the development of these gut microbial species and/or metabolites for use as probiotics should be explored.…”

Effect of Microgravity on the Gut Microbiota Bacterial Composition in a Hindlimb Unloading Model

“…Various reports indicate that the microbiome can impart protection against many disorders, such as systemic metabolic disease (type 2 diabetes and obesity), inflammatory bowel disease, eczema, and allergic diseases, whereas dysbiosis in the gut, can in turn, lead to the development of disease as well as affect the immune system [24][25][26]. The role of the gut microbiome in astronaut health is only recently becoming apparent, as depicted in the NASA twins study which revealed decreases in bacterial diversity and the overall composition of the gut microbiome was affected, but the precise effects on astronaut health are unknown [27]. Moreover, the study of the gut microbiome in astronauts has limitations.…”

Microbiome and One Health: Potential of Novel Metabolites from the Gut Microbiome of Unique Species for Human Health

“…Thus, the development of strategies to restore gut microbial diversity and maintain the precise ratios of bacterial species within the gut for optimal health are required and should be investigated in future space missions as well as in analog missions, or ground based in vivo and in vitro models of microgravity/stress/ageing or various models of disease. Increased understanding of the novel molecules produced by fascinating species such as cockroaches and crocodiles and their precise and detailed effects on ageing, longevity, cancer, cellular senescence or overall human health are warranted [ 15 ]. Recent studies have depicted the potent anticancer and antibacterial nature of molecules from these species [ 26 ].…”

“…Studying the gut microbiome of animals has received much less attention. Nonetheless, with the awareness of the concept of one health, which refers to the connection of human, animal, plant, and environmental health, it is logical to investigate the gut microbiome of unique and interesting animals such as long-lived animals including reptiles who have evolved, adapted and survived successfully over millions of years, dwelling in often harsh environments containing heavy metals and coming across radiation [ 15 ]. Other species such as cockroaches are of interest, given their status as one of the most successful and diverse insects.…”