Person: Ma, Siming
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Ma
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Siming
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Ma, Siming
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Publication Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino acid status(2014) Lee, Byung Cheon; Kaya, Alaattin; Ma, Siming; Kim, Gwansu; Gerashchenko, Maxim; Yim, Sun Hee; Hu, Zhen; Harshman, Lawrence G.; Gladyshev, VadimReduced methionine (Met) intake can extend lifespan of rodents, but whether this regimen represents a general strategy for regulating aging has been controversial. Here we report that Met restriction extends lifespan in both fruit flies and yeast, and that this effect requires low amino acid status. Met restriction in Drosophila mimicks the effect of dietary restriction and is associated with decreased reproduction. However, under conditions of high amino acid status, Met restriction is ineffective and the trade-off between longevity and reproduction is not observed. Overexpression of InRDN or Tsc2 inhibits lifespan extension by Met restriction, suggesting the role of TOR signaling in the Met control of longevity. Overall, this study defines the specific roles of Met and amino acid imbalance in aging and suggests that Met restiction is a general strategy for lifespan extension.Publication Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation(eLife Sciences Publications, Ltd, 2014) Avanesov, Andrei S.; Ma, Siming; Pierce, Kerry A; Yim, Sun Hee; Lee, Byung Cheon; Clish, Clary B; Gladyshev, VadimAging is thought to be associated with increased molecular damage, but representative markers vary across conditions and organisms, making it difficult to assess properties of cumulative damage throughout lifespan. We used nontargeted metabolite profiling to follow age-associated trajectories of >15,000 metabolites in Drosophila subjected to control and lifespan-extending diets. We find that aging is associated with increased metabolite diversity and low-abundance molecules, suggesting they include cumulative damage. Remarkably, the number of detected compounds leveled-off in late-life, and this pattern associated with survivorship. Fourteen percent of metabolites showed age-associated changes, which decelerated in late-life and long-lived flies. In contrast, known metabolites changed in abundance similarly to nontargeted metabolites and transcripts, but did not increase in diversity. Targeted profiling also revealed slower metabolism and accumulation of lifespan-limiting molecules. Thus, aging is characterized by gradual metabolome remodeling, and condition- and advanced age-associated deceleration of this remodeling is linked to mortality and molecular damage. DOI: http://dx.doi.org/10.7554/eLife.02077.001Publication Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii(Nature Pub. Group, 2013) Seim, Inge; Fang, Xiaodong; Xiong, Zhiqiang; Lobanov, Alexey V.; Huang, Zhiyong; Ma, Siming; Feng, Yue; Turanov, Anton A.; Zhu, Yabing; Lenz, Tobias Leander; Gerashchenko, Maxim V.; Fan, Dingding; Hee Yim, Sun; Yao, Xiaoming; Jordan, Daniel Michael; Xiong, Yingqi; Ma, Yong; Lyapunov, Andrey N.; Chen, Guanxing; Kulakova, Oksana I.; Sun, Yudong; Lee, Sang-Goo; Bronson, Roderick; Moskalev, Alexey A.; Sunyaev, Shamil; Zhang, Guojie; Krogh, Anders; Wang, Jun; Gladyshev, VadimBats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt’s bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4–8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity. Here we report sequencing and analysis of the Brandt’s bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function. Unique sequence changes in growth hormone and insulin-like growth factor 1 receptors are also observed. The data suggest that an altered growth hormone/insulin-like growth factor 1 axis, which may be common to other long-lived bat species, together with adaptations such as hibernation and low reproductive rate, contribute to the exceptional lifespan of the Brandt’s bat.Publication The transcriptome of the bowhead whale Balaena mysticetus reveals adaptations of the longest-lived mammal(Impact Journals LLC, 2014) Seim, Inge; Ma, Siming; Zhou, Xuming; Gerashchenko, Maxim; Lee, Sang-Goo; Suydam, Robert; George, John C.; Bickham, John W.; Gladyshev, VadimMammals vary dramatically in lifespan, by at least two-orders of magnitude, but the molecular basis for this difference remains largely unknown. The bowhead whale Balaena mysticetus is the longest-lived mammal known, with an estimated maximal lifespan in excess of two hundred years. It is also one of the two largest animals and the most cold-adapted baleen whale species. Here, we report the first genome-wide gene expression analyses of the bowhead whale, based on the de novo assembly of its transcriptome. Bowhead whale or cetacean-specific changes in gene expression were identified in the liver, kidney and heart, and complemented with analyses of positively selected genes. Changes associated with altered insulin signaling and other gene expression patterns could help explain the remarkable longevity of bowhead whales as well as their adaptation to a lipid-rich diet. The data also reveal parallels in candidate longevity adaptations of the bowhead whale, naked mole rat and Brandt's bat. The bowhead whale transcriptome is a valuable resource for the study of this remarkable animal, including the evolution of longevity and its important correlates such as resistance to cancer and other diseases.Publication Molecular Patterns and Signatures of Longevity(2016-05-02) Ma, Siming; Sinclair, David A.; Gladyshev, Vadim N.; Church, George M.; Sunyaev, Shamil R.Since their divergence from a common ancestor some 200 million years ago, mammals have undergone significant diversification in physiology, morphology, habitat, size, and longevity. The maximum lifespan of mammalian species ranges from under 3 to over 200 years, but the molecular basis of such variation is poorly understood. While many genes, pathways, dietary interventions, and pharmacological compounds have been shown to influence the lifespan of model organisms, it is not known whether the same mechanisms are responsible for the longevity variation across different species. This thesis presents the analyses of gene expression and the levels of metabolites, chemical elements, and/or proteins, across multiple organs and tissues of up to 42 species of mammals, as well as the analyses of 5 long-lived mouse models, 22 natural isolates of yeast, and 16 species of fruit flies, to identify the molecular patterns and signatures associated with species longevity. The results show that longer-lived mammals up-regulate ribosomal proteins and genes involved in DNA repair, and down-regulate ubiquitin-mediated proteolysis and apoptotic functions. Some of the metabolic changes in long-lived mammals, such as higher levels of sphingomyelins and glycerophospholipids but lower levels of polyunsaturated triacylglycerols, were also observed in long-lived mouse models. Yeast strains of varying replicative lifespan differed in their aerobic respiration capacity, attributable to different protein composition in mitochondria. Long-lived fruit flies overexpressed the genes involved in lipid metabolism but suppressed the genes involved in neuronal development. Many genes previously implicated in lifespan control in model organisms also showed the expected correlation with the longevity traits across species. This thesis presents the snapshots of the complex changes associated with species natural lifespan variation and offers new insights into the mechanisms of longevity control and potential lifespan extension strategies.