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Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive Aug 15, 2013

 

HLH-30/TFEB appears flourescent within these C. elegans worms.

Credit: Sanford-Burnham Medical Research Institute






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Key protein identified that affects aging

New findings could lead to the development of therapeutic agents for age-related diseases.

Scientists at Sanford-Burnham Medical Research Institute have identified a key factor that regulates autophagy, the process of cleansing cells from waste material and cellular debris.

The findings, published in Nature Communications today, could lead to the development of new therapies for age-related disorders that are characterized by a breakdown in this process.


Malene Hansen, Ph.D., associate professor in Sanford-Burnham's Del E. Webb Center for Neuroscience, Aging and Stem Cell Research, and her team as well as collaborators found a transcription factor—an on/off switch for genes—that induces autophagy in animal models, including the nematode C. elegans, the primary model organism studied in the Hansen lab.


This transcription factor, called HLH-30, coordinates the autophagy process by regulating genes with functions in different steps of the process. Two years ago, researchers discovered a similar transcription factor, or orthologue, called TFEB that regulates autophagy in mammalian cells.

"HLH-30 is critical to ensure longevity in all of the long-lived C. elegans strains we tested. These models require active HLH-30 to extend lifespan, possibly by inducing autophagy. We found this activation not only in worm longevity models, but also in dietary-restricted mice, and we propose the mechanism might be conserved in higher organisms as well,"says Hansen.

HLH-30 is the first transcription factor reported to function in all known autophagy-dependent longevity paradigms, strengthening the emerging concept that autophagy can contribute to long lifespan. In a previous study, Hansen and her colleagues discovered that increased autophagy has an anti-aging effect, possibly by promoting the activity of an autophagy-related, fat-digesting enzyme. With these findings, scientists now know a key component of the regulation of autophagy in aging.


Hansen's team is now working to find therapeutic targets, particularly upstream kinases, molecules that change protein function, which might actually phosphorylate the transcription factor to alter its function.


"We already have a clue about the protein TOR, a master regulator that influences metabolism and aging in many species, but there might be other kinases that regulate HLH-30 or TFEB activity as well," says lead study author Louis René Lapierre, Ph.D., a postdoctoral fellow in Hansen's laboratory, and a recent recipient of a K99/R00 Pathway to Independence career award from the National Institutes of Health.

Autophagy has become the subject of intense scientific scrutiny over the past few years, particularly since the process—or its malfunction—is implicated in many human diseases, including cancer, Alzheimer's, as well as cardiovascular disease and neurodegenerative disorders.

HLH-30 and TFEB may represent attractive targets for the development of new therapeutic agents against such diseases.

Abstract not available.

The research was funded by the National Institutes of Health (P50 AG005131), the National Institute on Aging (F31 AG029222, R01 AG038664, R01 AG039756), the NIGMS (R01 GM101056).

The study was co-authored by C. Daniel De Magalhaes Filho, Glenn Center for Aging, Salk Institute for Biological Studies; Philip R. McQuary, Sanford-Burnham; Chu-Chiao Chu, Sanford-Burnham; Jessica T. Chang, Sanford-Burnham; Sara Gelino, Sanford-Burnham; Binnan Ong, Sanford-Burnham; Andrew E. Davis, Sanford-Burnham; Javier E. Irazoqui, Harvard Medical School; and Andrew Dillin, Glenn Center for Aging, Salk Institute for Biological Studies.

About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of diseases and devising the innovative therapies of tomorrow. Sanford-Burnham takes a collaborative approach to medical research with major programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory and childhood diseases. The Institute is recognized for its National Cancer Institute-designated Cancer Center and expertise in drug discovery technologies. Sanford-Burnham is a nonprofit, independent institute that employs 1,200 scientists and staff in San Diego (La Jolla), California, and Orlando (Lake Nona), Florida. For more information, visit us at http://www.sanfordburnham.org.

Original press release: http://www.eurekalert.org/pub_releases/2013-08/smri-ssi080513.php