scispace - formally typeset
Search or ask a question
Author

Ramon Tabtiang

Bio: Ramon Tabtiang is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Gene & Reporter gene. The author has an hindex of 2, co-authored 3 publications receiving 2968 citations.

Papers
More filters
Journal ArticleDOI
02 Dec 1993-Nature
TL;DR: Finding that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type raises the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation.
Abstract: We have found that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type. This lifespan extension, the largest yet reported in any organism, requires the activity of a second gene, daf-16. Both genes also regulate formation of the dauer larva, a developmentally arrested larval form that is induced by crowding and starvation and is very long-lived. Our findings raise the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation. daf-2 and daf-16 provide entry points into understanding how lifespan can be extended.

3,146 citations

Journal ArticleDOI
TL;DR: The results suggest that Nut1p, Nut2p, Sin4p, and Ccr4p define a group of proteins that negatively regulate transcription in a subtle manner which is revealed by artificial reporter genes.
Abstract: The URS2 region of the Saccharomyces cerevisiae HO upstream region contains 10 binding sites for the Swi4p/Swi6p transcription factor and confers Swi4p dependence for transcription. Using a hybrid promoter, UASGAL (upstream activation sequence of GAL1)-URS2R, in which the GAL1-10 regulatory region is fused to the proximal 360 bp of URS2, we isolated mutants in which Swi4p is no longer required for transcription. Mutations of SIN4, ROX3, SRB8, SRB9, SRB10, SRB11, and two novel genes, NUT1 and NUT2, relieve the requirement of Swi4p for expression of this reporter. We found that NUT1 (open reading frame [ORF] YGL151w) is a nonessential gene, that NUT2 (ORF YPR168w) is essential, and that both Nut1p and Nut2p encode nuclear proteins. Deletion of NUT1 causes a constitutive, Swi4p-independent phenotype only in combination with the nut2-1 allele or an allele of CCR4. In contrast, inactivation of a temperature-sensitive allele of NUT2, nut2-ts70, alone causes constitutivity. nut1Δ nut2-1 cells and sin4Δ cells exhibit Swi4p-independent expression of an ho-lacZ reporter but not of an intact ho gene. Likewise, a pPHO5-lacZ construct is constitutively expressed in nut1 nut2 mutants relative to their wild-type counterparts. These results suggest that Nut1p, Nut2p, Sin4p, and Ccr4p define a group of proteins that negatively regulate transcription in a subtle manner which is revealed by artificial reporter genes.

51 citations

01 Jan 2005
TL;DR: The history of science is pockmarked with such sudden appearances of new fields of research that historians will wonder how the process of understanding ageing really began: why is it that classical genetic studies of lifespan only really began in the 1990s?
Abstract: A mutation which doubles C. elegans life span (imagine being 140). Worm Breeder's Gazette 12 (5): 94. A source of fascination for historians is the way that particular cultural movements or traditions, conflicts and so forth spring onto the scene, seemingly out of nowhere. I remember wondering as a boy during the 1960s where rock and roll music had come from. From watching television it seemed to me that after a long prehistory of Bing Crosby and Frank Sinatra, by some extraordinary process there had suddenly appeared, ex nihilo, the Beatles and Herman's Hermits. Such miraculous births are a popular topic for scientific historians. Arthur Koestler, for example, wondered about the renaissance of cosmology after the dark ages, and the origins of modern physics: how did the process begin that led to Isaac Newton and Albert Einstein? Koestler dismissed Copernicus as a medievalist who just happened to be right with his heliocentric theory. For Koestler the first recognisably modern physicist was Johannes Kepler, who devised his three laws of planetary motion in the early 1600s. Much of Koestler's book The Sleepwalkers is dedicated to exploring how someone like Kepler could exist, a man so much a child of the dark ages (he narrowly rescued his mother from being burned as a witch). How was it that he wandered out of the medieval darkness? The history of science is pockmarked with such sudden appearances of new fields of research. One such is the recent emergence of lifespan genetics – the topic of my own research. Perhaps at some future time, when the biology of ageing is long since fully elucidated, and treatments for ageing-related diseases such as cardiovascular disease and ageing-related cancers and dementias is routine, historians will wonder how the process of understanding ageing really began. While the biology of the ageing process remains largely mysterious, it has always been obvious that longevity is largely under genetic control: different animal species have very different lifespans, even when protected from external causes of mortality. This has to be a function of their genome. If lifespan is genetically determined in the same way as, say development, morphology, behaviour, why is it that classical genetic studies of lifespan only really began in the 1990s? After all, ageing is an interesting topic, since for most of us it represents our death. On the face of it, in failing to examine the genetics of ageing …

Cited by
More filters
Journal ArticleDOI
06 Jun 2013-Cell
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.

9,980 citations

Journal ArticleDOI
TL;DR: In light of the recent advances in understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, the exciting therapeutic opportunities for targeting this pathway to treat these diseases are discussed.
Abstract: Phosphatidylinositol 3-kinases (PI3Ks) evolved from a single enzyme that regulates vesicle trafficking in unicellular eukaryotes into a family of enzymes that regulate cellular metabolism and growth in multicellular organisms. In this review, we examine how the PI3K pathway has evolved to control these fundamental processes, and how this pathway is in turn regulated by intricate feedback and crosstalk mechanisms. In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases.

2,935 citations

Journal ArticleDOI
24 Mar 2010-Nature
TL;DR: The nematode Caenorhabditis elegans ages and dies in a few weeks, but humans can live for 100 years or more, which means that over evolutionary time mutations have increased lifespan more than 2,000-fold.
Abstract: The nematode Caenorhabditis elegans ages and dies in a few weeks, but humans can live for 100 years or more. Assuming that the ancestor we share with nematodes aged rapidly, this means that over evolutionary time mutations have increased lifespan more than 2,000-fold. Which genes can extend lifespan? Can we augment their activities and live even longer? After centuries of wistful poetry and wild imagination, we are now getting answers, often unexpected ones, to these fundamental questions.

2,466 citations

Journal ArticleDOI
10 May 2002-Science
TL;DR: The evidence presented in this paper suggests that the apparent leveling off of life expectancy in various countries is an artifact of laggards catching up and leaders falling behind, not a sign that life expectancy is approaching its limit.
Abstract: Is human life expectancy approaching its limit? Many--including individuals planning their retirement and officials responsible for health and social policy--believe it is, but the evidence presented in the Policy Forum suggests otherwise. For 160 years, best-performance life expectancy has steadily increased by a quarter of a year per year, an extraordinary constancy of human achievement. Mortality experts have repeatedly asserted that life expectancy is close to an ultimate ceiling; these experts have repeatedly been proven wrong. The apparent leveling off of life expectancy in various countries is an artifact of laggards catching up and leaders falling behind.

2,462 citations

Journal ArticleDOI
15 Aug 1997-Science
TL;DR: 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.
Abstract: 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.

2,167 citations