About

Stephen L. Helfand is the George D. Eggleston Endowed Professor of Biochemistry and a Professor in the Department of Molecular Biology, Cell Biology and Biochemistry at Brown University. He also serves as Vice Chair for Research in the Department of Neurology. His research focuses on understanding the molecular genetic mechanisms underlying aging and longevity, primarily using the model system Drosophila melanogaster. Helfand's academic background includes a BS from Stanford University, where he worked with Dr. Norman K. Wessells and discovered the neuronal growth factor later renamed Ciliary Neurotrophic Factor, and an MD from Albert Einstein College of Medicine. He completed his Medical Internship at Montefiore Medical Center and Neurology Residency at Massachusetts General Hospital, and is Board Certified in Neurology. His postdoctoral training included work with Drs. Corey Goodman and David Hogness at Stanford and with John Carlson at Yale. Helfand has held positions at the University of Connecticut Health Center before joining Brown University in 2005. His laboratory's research aims to elucidate the molecular mechanisms of aging, with notable contributions recognized through awards such as the MERIT award from the National Institute on Aging, the Glenn Award for Research in Biological Mechanisms of Aging, and the Glenn Foundation/American Federation of Aging Research Breakthroughs in Gerontology Award. He has been elected a Fellow of the AAAS and the Gerontological Society of America, and in 2019, he was elected Chair Elect for the Biological Science Section of the Gerontological Society of America. Helfand is also involved with several research centers and committees at Brown University, contributing to the fields of molecular biology, neurobiology, and aging.

Research topics

• Biology
• Genetics
• Evolutionary biology
• Computational biology

Selected publications

• The Fourth Annual Symposium of the Midwest Aging Consortium

  The Journals of Gerontology Series A · 2024-11-01 · 1 citations

  articleOpen access

  The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023. The symposium featured presentations on a wide array of topics, including studies on slow-aging animals, cellular senescence and senotherapeutics, the role of the immune system in aging, metabolic changes in aging, neuronal health in aging, and biomarkers for measuring the aging process. Speakers shared findings from studies involving a variety of animals, ranging from commonly used species such as mice, rats, worms, yeast, and fruit flies, to less-common ones like naked mole-rats, painted turtles, and rotifers. MAC continues to emphasize the importance of supporting emerging researchers and fostering a collaborative environment, positioning itself as a leader in aging research. This symposium not only showcased the current state of aging biology research but also highlighted the consortium's role in training the next generation of scientists dedicated to improving the healthspan and well-being of the aging population.

  PublisherOA PDFDOI

• A specialized metabolic pathway partitions citrate in hydroxyapatite to impact mineralization of bones and teeth

  Proceedings of the National Academy of Sciences · 2022-11-02 · 45 citations

  articleOpen access

  Citrate is a critical metabolic substrate and key regulator of energy metabolism in mammalian cells. It has been known for decades that the skeleton contains most (>85%) of the body’s citrate, but the question of why and how this metabolite should be partitioned in bone has received singularly little attention. Here, we show that osteoblasts use a specialized metabolic pathway to regulate uptake, endogenous production, and the deposition of citrate into bone. Osteoblasts express high levels of the membranous Na + -dependent citrate transporter solute carrier family 13 member 5 ( Slc13a5 ) gene. Inhibition or genetic disruption of Slc13a5 reduced osteogenic citrate uptake and disrupted mineral nodule formation. Bones from mice lacking Slc13a5 globally, or selectively in osteoblasts, showed equivalent reductions in cortical thickness, with similarly compromised mechanical strength. Surprisingly, citrate content in mineral from Slc13a5 −/− osteoblasts was increased fourfold relative to controls, suggesting the engagement of compensatory mechanisms to augment endogenous citrate production. Indeed, through the coordinated functioning of the apical membrane citrate transporter SLC13A5 and a mitochondrial zinc transporter protein (ZIP1; encoded by Slc39a1 ), a mediator of citrate efflux from the tricarboxylic acid cycle, SLC13A5 mediates citrate entry from blood and its activity exerts homeostatic control of cytoplasmic citrate. Intriguingly, Slc13a5 -deficient mice also exhibited defective tooth enamel and dentin formation, a clinical feature, which we show is recapitulated in primary teeth from children with SLC13A5 mutations. Together, our results reveal the components of an osteoblast metabolic pathway, which affects bone strength by regulating citrate deposition into mineral hydroxyapatite.

  PublisherOA PDFDOI

• Sirt6 regulates lifespan in <i>Drosophila melanogaster</i>

  Proceedings of the National Academy of Sciences · 2022 · 51 citations

  Senior authorCorresponding
  • Biology
  • Evolutionary biology
  • Genetics

  Significance Sirt6 is well known for its role in regulating the aging process, particularly for its ability to extend lifespan in mice when overexpressed. However, the underlying molecular mechanisms responsible for lifespan regulation by Sirt6 are not well understood. Here, we characterized dSirt6 in fruit flies ( Drosophila melanogaster ). We found that dSirt6 functions very similarly to mammalian Sirt6 at the molecular and biochemical levels. Furthermore, overexpressing dSirt6 increased lifespan in flies. dSirt6 overexpression extends lifespan, in part, by opposing the activity of Myc, a master regulator of protein synthesis, which is associated with decreased protein synthesis. These findings have relevance for the treatment of age-related disease by modulating Sirt6 activity.

  PublisherDOI

• The role of retrotransposable elements in ageing and age-associated diseases

  Nature · 2021 · 427 citations

  • Biology
  • Evolutionary biology
  • Genetics
  PublisherOA PDFDOI

• Evidence that overnight fasting could extend healthy lifespan

  Nature · 2021-09-29 · 4 citations

  letter1st authorCorresponding
  PublisherDOI

• The longevity gene mIndy (I’m Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms

  JCI Insight · 2021-01-24 · 21 citations

  articleOpen access

  Reduced expression of the plasma membrane citrate transporter INDY (acronym I'm Not Dead, Yet) extends life span in lower organisms. Deletion of the mammalian Indy (mIndy) gene in rodents improves metabolism via mechanisms akin to caloric restriction, known to lower blood pressure (BP) by sympathoadrenal inhibition. We hypothesized that mIndy deletion attenuates sympathoadrenal support of BP. Continuous arterial BP and heart rate (HR) were reduced in mINDY-KO mice. Concomitantly, urinary catecholamine content was lower, and the decreases in BP and HR by mIndy deletion were attenuated after autonomic ganglionic blockade. Catecholamine biosynthesis pathways were reduced in mINDY-KO adrenals using unbiased microarray analysis. Citrate, the main mINDY substrate, increased catecholamine content in pheochromocytoma cells, while pharmacological inhibition of citrate uptake blunted the effect. Our data suggest that deletion of mIndy reduces sympathoadrenal support of BP and HR by attenuating catecholamine biosynthesis. Deletion of mIndy recapitulates beneficial cardiovascular and metabolic responses to caloric restriction, making it an attractive therapeutic target.

  PublisherOA PDFDOI

• Impact papers on aging in 2009

  UNC Libraries · 2020-10-30

  articleOpen access

  The editorial board of Aging reviews research papers published in 2009, which they believe have or will have a significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, DNA damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacologic interventions into aging. The emerging message in 2009 is that aging is not random but determined by a genetically-regulated longevity network and can be decelerated both genetically and pharmacologically.

  PublisherDOI

• Mechanisms of Lifespan Extension by Sirt6 in Drosophila melanogaster

  Innovation in Aging · 2020-12-01

  articleOpen accessSenior author

  Abstract Sirt6 is a multifunctional enzyme that regulates numerous cellular processes connected to longevity. Overexpressing Sirt6 extends lifespan in mice, but the underlying cellular mechanisms are unclear. Here, we used the powerful genetic tools and short lifespan of Drosophila melanogaster to better understand the precise mechanisms by which Sirt6 regulates longevity. Sirt6 OE in flies produces robust extension of median lifespan in both sexes. Molecular and biochemical analyses reveal that Sirt6 OE reduces expression of genes involved in protein synthesis, including many Myc target genes, via epigenetic regulation. We will further discuss our findings on the connection between Sirt6, Myc, and the molecular regulation of protein synthesis and lifespan, as well as additional Sirt6 longevity mechanisms we identified, including autophagy and silencing of transposable elements.

  PublisherOA PDFDOI

• The Future of Aging Research

  Innovation in Aging · 2020-12-01

  articleOpen access1st authorCorresponding

  Abstract We are at a particularly propitious time in the history of the biology of aging and the science of health and humanity. It is a time for us to “Honor the Past, Enrich the Future”. Not long ago the study of the biology of aging was exclusively one of description of what happened with age—how do organisms, including humans, change with age at the level of proteins, cells, tissues and physiology. The identification of major genetic factors that substantially increase life span in model organisms ushered in the advent of a highly exploratory period focusing on the molecular, cellular and genetics mechanisms of aging. The convergence of many different streams of basic and clinical research have brought us to today, where we stand on the cusp of new environmental, molecular genetic and pharmacological breakthroughs in the biology of aging that presage new interventions that promise a healthier lifespan. The presentations in this Presidential Symposium will be from four Early Career Investigators presenting their own pioneering research in some of the most important areas of research in the biology of aging.

  PublisherOA PDFDOI

• LINE1 Derepression in Aged Wild-Type and SIRT6-Deficient Mice Drives Inflammation

  Cell Metabolism · 2019-03-07 · 493 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant K11HD000736

  NIH · $318k · 1989

• NIH Grant R01AG025277

  NIH · $1.5M · 2011

• Control of Gene Expression and Life Span

  NIH · $5.5M · 2004–2019

• NIH Grant R37AG016667

  NIH · $3.8M · 2016

• NIH Grant R01AG016667

  NIH · $1.5M · 2004

Frequent coauthors

• Nicola Neretti

  Providence College

  65 shared

• Andreas L. Birkenfeld

  German Center for Diabetes Research

  58 shared

• Jason G. Wood

  Providence College

  51 shared

• W Ruehl

  Urbana University

  50 shared

• Cheng-Yi Chang

  Taichung Hospital

  50 shared

• Blanka Rogina

  UConn Health

  43 shared

• John M. Sedivy

  Brown University

  33 shared

• Johannes H. Bauer

  Klinikum Brandenburg

  32 shared

Education

• B.S.

  Stanford University

• M.D.

  Albert Einstein College of Medicine

• Other, Department of Zoology

  UC London

• Other

  Stanford University

• Other

  Yale University

Awards & honors

• Ellison Medical Foundation Senior Scholar
• MERIT award from the National Institute on Aging
• Glenn Award for Research in Biological Mechanisms of Aging (…
• Glenn Foundation/American Federation of Aging Research Break…
• Fellow of the AAAS (2017)