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      Longevity: Lesson from Model Organisms

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          Abstract

          Research on longevity and healthy aging promises to increase our lifespan and decrease the burden of degenerative diseases with important social and economic effects. Many aging theories have been proposed, and important aging pathways have been discovered. Model organisms have had a crucial role in this process because of their short lifespan, cheap maintenance, and manipulation possibilities. Yeasts, worms, fruit flies, or mammalian models such as mice, monkeys, and recently, dogs, have helped shed light on aging processes. Genes and molecular mechanisms that were found to be critical in simple eukaryotic cells and species have been confirmed in humans mainly by the functional analysis of mammalian orthologues. Here, we review conserved aging mechanisms discovered in different model systems that are implicated in human longevity as well and that could be the target of anti-aging interventions in human.

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          Most cited references145

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          RAS Proteins and Their Regulators in Human Disease.

          RAS proteins are binary switches, cycling between ON and OFF states during signal transduction. These switches are normally tightly controlled, but in RAS-related diseases, such as cancer, RASopathies, and many psychiatric disorders, mutations in the RAS genes or their regulators render RAS proteins persistently active. The structural basis of the switch and many of the pathways that RAS controls are well known, but the precise mechanisms by which RAS proteins function are less clear. All RAS biology occurs in membranes: a precise understanding of RAS' interaction with membranes is essential to understand RAS action and to intervene in RAS-driven diseases.
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            daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans.

            A C. elegans neurosecretory signaling system regulates whether animals enter the reproductive life cycle or arrest development at the long-lived dauer diapause stage. daf-2, a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member. Decreases in DAF-2 signaling induce metabolic and developmental changes, as in mammalian metabolic control by the insulin receptor. Decreased DAF-2 signaling also causes an increase in life-span. Life-span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity.
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              Evolutionary and biomedical insights from the rhesus macaque genome.

              The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                09 July 2019
                July 2019
                : 10
                : 7
                : 518
                Affiliations
                Dipartimento di Discipline Chirurgiche, Oncologiche e Stomatologiche, Università di Palermo, Via del Vespro 129, 90100 Palermo, Italy
                Author notes
                Author information
                https://orcid.org/0000-0002-7530-1516
                Article
                genes-10-00518
                10.3390/genes10070518
                6678192
                31324014
                be06356d-9715-46fd-a95e-128059a5c892
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 April 2019
                : 02 July 2019
                Categories
                Review

                model systems,aging,signal transduction,molecular senescence

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