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  • Derek M. Huffman, Ph.D.

Derek M. Huffman, Ph.D.

Derek M. Huffman

Associate Professor, Department of Molecular Pharmacology

Associate Professor, Department of Medicine (Endocrinology)

Contact Information

718.430.4278718.430.8557derek.huffman@einsteinmed.edu

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Golding Building, Room 201
Bronx, NY 10461

Research Profiles

More Resources: Department of Molecular Pharmacology

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Professional Interests

Dr. Huffman is an Assistant Professor of Medicine and Molecular Pharmacology, Co-Director of the Einstein Healthy Aging Physiology Core, and Member of the Einstein Aging Center, Cancer Center, and Diabetes Research Center at the Albert Einstein College of Medicine. Dr. Huffman’s research is focused on three areas:

  1. The biology of aging: role of IGF-1 signaling
  2. Central insulin and IGF-1 signaling
  3. Role of obesity and aging on cancer risk

1) The biology of aging: role of IGF-1 signaling – I am primarily interested in understanding the interplay between endocrine and metabolic systems with aging and age-related diseases. There is a clear link between aging and metabolism across species. In mammalians, aging is characterized metabolically by accretion of visceral fat, insulin resistance, dyslipidemias and metabolic inflexibility. This dysregulation in metabolism has been linked to increased risk for numerous age-related diseases and accelerated aging. Likewise, growth factors and body size have been closely tied to lifespan. Indeed, dwarf mice live longer than normal mice, small dogs live longer than large dogs, and ponies live longer than thoroughbreds. This phenomenon is believed to be attributed to a reduction in growth hormone (GH)/insulin-like growth factor-1 (IGF-1) signaling, and less signaling through this axis has been has been linked to improved longevity in model organisms. Furthermore, in humans, high IGF-1 levels are associated with increased cancer risk, but are paradoxically linked with protection from cardiovascular disease, type 2 diabetes and osteoporosis. Thus, the relevance of IGF-1 to aging in humans remains unclear.

Relevant to this paradox, we have recently uncovered novel, beneficial effects of centrally-acting IGF-1 on peripheral metabolism. Furthermore, we have found that as compared to central insulin treatment, central IGF-1 replacement in old, insulin-resistant rats, more effectively restores peripheral insulin action. This has led us to hypothesize that optimally modulating IGF-1 signaling to promote healthy aging and longevity in humans may require shifting the balance of IGF-1 from the periphery to the central nervous system (CNS) in order to maximize the 'good' effects of IGF-1, while minimizing its 'bad' effects on cancer in the periphery. We are currently testing this hypothesis in animal models using a combination of genetic and pharmacologic approaches, combined with several state-of-the-art strategies to evaluate healthy aging in these animals. We are specifically evaluating the potential of IGF-1 receptor (IGF-1R) antibodies, currently used in clinical trials to treat cancer, as a pharmacologic strategy to reduce peripheral (but not central) IGF-1R signaling in hopes that this may serve as a translational tool for treating some manifestations of aging in humans, thus ""bridging the gap"" between basic biological discovery and human therapeutic strategy.

2) Central insulin and IGF-1 signaling – A second area involves understanding the mechanism(s) whereby insulin and IGF-1 signaling in the brain control peripheral metabolism. Ongoing studies have uncovered novel similarities and differences between insulin and IGF-1 in regards to their ability to regulate glucose metabolism via the CNS. These studies involve tandem central infusion of peptides and/or inhibitors during a euglycemic clamp in awake, unstressed animals. These studies thus far seem to suggest a potentially important role for insulin receptor/IGF-1R hybrids in the brain. In addition, aged animals demonstrate central insulin resistance, but respond remarkably well to central IGF-1, suggesting that IGF-1 may be a better ligand in the brain than insulin for treating some manifestations of aging. Studies are also ongoing using BOLD-fMRI to assess the impact of central insulin and IGF-1 in the brain as well as with Dr. Young-Hwan Jo on the role of insulin, IGF-1, and their receptors, on electrical activity in specific neuronal populations.

3) Role of obesity and aging on cancer risk – A third area involves the role of aging, obesity and diet on cancer risk. In a pre-clinical model of prostate cancer, we have previously found that cancer risk was linked to energy balance and body mass, but independent of food intake. Likewise, using a surgical model of visceral fat removal, we have found that ablating visceral fat stores in male rats extended their longevity, thus uncoupling the effects of fat from nutrients on lifespan for the first time. More recently, we have found that visceral fat removal is protective from adenoma development and improved survival in a female model of intestinal cancer, providing the first causal evidence linking adiposity to this site-specific cancer. Future areas of interest in this area include studies uncovering the mechanisms behind this link, to determine how abdominal obesity and nutrient availability act independently during the various stages of tumor promotion and progression. We are particularly interested in interrogating the epigenetic changes that occur in specific intestinal stem cells with obesity and aging and how these might relate to later cancer risk. We are also employing parabiosis surgery between young and old animals to assess the role of systemic factors from young and old environments on this process.

Selected Publications

Original Communications (selected)

Milman S, Atzmon G, Huffman DM, Wan J, Crandall JP, Cohen P and Barzilai N. Low Insulin-like Growth Factor-1 Level Predicts Survival in Humans with Exceptional Longevity. Aging Cell 2014 Aug;13(4):769-71 PMC4116456

Huffman DM, Farias-Quipildor G, Mao K, Zhang X, Wan J, Apontes P, Cohen P, Barzilai N. Central IGF-1 Restores Whole-Body Insulin Action in a Model of Age-Related Insulin Resistance and IGF-1 Decline Aging Cell. 2016 Feb;15(1):181-86. PMC4717281

Cobb LJ, Lee C, Xiao J, Yen K, Wong RG, Nakamura HK, Mehta HH, Gao Q, Ashur C, Huffman DM, Wan J, Muzumdar RH, Barzilai N, Cohen P. Naturally-occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers Aging 2016 Apr;8(4):796-809 PMC4925829

Tabrizian, T, Wang D, Guan F, Hu Z, Beck A, Delahaye F, Huffman DM. Apc inactivation, but not obesity, synergizes with Pten deficiency to drive intestinal stem cell-derived tumorigenesis. Endocr Relat Cancer 2017 Mar 28 PMC5505256

Burgos ES, Walters RO, Huffman DM, Shechter D. A simplified characterization of S-adenosyl-L-methionine-consuming enzymes with 1-Step EZ-MTase: a universal and straightforward coupled-assay for in vitro and in vivo setting. Chem Sci 2017 8, 6601-6612 PMC5676521

Hudgins AD, Tazearslan C, Tare A, Zhu Y, Huffman DM, Suh Y. Age- and tissue-specific expression of senescence biomarkers in mice. Front Genet 2018 Feb 23;9:59 PMC5829053

Andrew MS*, Huffman DM, Rodriguez-Ayala E, Kent JW, Nava-Gonzalez EJ, Jorge B, Williams NN, Lavianda-Molina HA, Peterson RM, Bastarrachea RA. Removal of Mesenteric Visceral Fat Reverses Insulin Resistance in Baboons. Surg Obes Relat Dis 2018 Mar 9. pii: S1550-7289(18)30127-8. PMC6391994

Mao K, Farias Quipildor G, Tabrizian T, Guan F, Walters RO, Delahaye F, Hubbard GB, Ikeno Y, Ejima K, Li P, Allison DB, Beltran P, Cohen P, Barzilai N, Huffman DM. Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nat Commun 2018 Jun 19;9(1):2394. PMC6008442

Guan F, Tabrizian T, Novaj A, Nakanishi M, Rosenberg DW, Huffman DM. Dietary walnuts protect against obesity-driven intestinal stem cell decline and tumorigenesis Front Nutr 2018 May 31;5:37. PMC5990619

Choi J, Rakhilin N, Gadamsetty P, Joe DJ, Lipkin SM, Tabrizian T, Huffman DM, Shen X, Nishimura N. Rapid recovery of crypt patterns after focal damage requires coordinated cell motion instead of proliferation and is impaired by aging. Sci Rep 2018 Jul 20;8(1):10989. PMC6054609

Walters RO, Arias E, Diaz A, Burgos ES, Guan F, Tiano S, Mao K, Green CL, Qiu Y, Shah H, Wang D, Hudgins AD, Tabrizian T, Tosti V, Shechter D, Fontana L, Kurland IJ, Barzilai N, Cuervo AM, Promislow DEL, Huffman DM. Sarcosine is uniquely modulated by aging and dietary restriction in rodents and humans Cell Rep 2018 Oct 16;25(3):663-676.e6. PMC6280974

Farias-Quipildor G, Mao K, Hu Z, Novaj A, Cui MH, Gulinello M, Branch CA, Gubbi S, Patel K, Moellering DR, Tarantini S, Kiss T, Yabluchanskiy A, Ungvari Z, Sonntag WE, Huffman DM. Central IGF-1 reduces depressive-like behavior and improves cognitive and physical performance with aging preferentially in male mice Geroscience 2019 May 10 PMC6544744

Morrison EJ, Champagne DP, Dzieciatkowska M, Nemkov T, Zimring JC, Hansen KC, Guan F, Huffman DM, Santambrogio L, D'Alessandro A. Parabiosis Incompletely Reverses Aging-Induced Metabolic Changes and Oxidant Stress in Mouse Red Blood Cells. Nutrients. 2019 Jun 14;11(6). pii: E1337. PMC6627295

Book Chapters, Reviews and Editorials

Huffman DM and Barzilai N. Animal Models of Visceral Obesity. Book Chapter from Abdominal Obesity and the Endocannabinoid System: From Basic Aspects to Clinical Management of Related Cardiometabolic Risk. Editor: Jean-Pierre Despres, PhD. Informa Healthcare.

Barzilai N, Huffman DM, Cohen P and Muzumdar RH. The role of IGF-1 and its partners in central and peripheral metabolism: Considerations for extending healthy lifespan. Book Chapter from Research and Perspectives in Endocrine Interactions: IGFs: Local Repair and Survival Factors Throughout the Life Span. Springer Publishing.

Huffman DM and Barzilai N. Contribution of Adipose Tissue to Health-Span and Longevity. Book Chapter from Body Composition and Aging. Editor: Charles Mobbs, PhD, Karger Publishing. Interdiscip Top Gerontol. 2010;37:1-19.

Huffman DM. Exercise as a Calorie Restriction Mimetic: Implications for Improving Healthy Aging and Longevity. Book Chapter from Body Composition and Aging. Editor: Charles Mobbs, PhD, Karger Publishing. Interdiscip Top Gerontol. 2010;37:157-174.

Huffman DM and Barzilai N. Role of visceral adipose tissue in aging. (Invited review) Biochemical and Molecular Mechanisms of Aging: from Model Systems to Human Longevity. Biochemica et Biophysica Acta 2009 Oct; 1790(10):1117-23. PMCID: PMC2779572

Huffman DM and Calvert JW. Exercise to the rescue. J Physiol 2011 589(24): 5919-5920. PMC3286671

Barzilai N, Huffman DM, Muzumdar RH, and Bartke A. Perspectives in Diabetes: The Critical Role of Metabolic Pathways in Aging. Diabetes 2012 61(6): 1315-22. PMCID: PMC3357299

Huffman DM. Editorial Comment to Inhibition of cortactin and SIRT1 expression attenuates migration and invasion of prostate cancer DU145 cells: Making sense of SIRT1 and prostate cancer. Int J Urol 2012 19(1) 79-80.

Denis GV, Huffman DM, and LeBrasseur NK. The Biology of Aging: Role in Cancer, Metabolic Dysfunction and Health Disparities. Book Chapter from Energy Balance and Cancer. Editors: Deborah J. Bowen, Gerald V. Denis, Nathan A. Berger. Springer 2014

Chusyd DE, Wang D, Huffman DM, Nagy TR. Relationships between rodent white adipose fat pads and human white adipose fat depots Front Nutr 2016 Apr 19;3:10 PMC4835715

Huffman DM, Schafer MJ, LeBrasseur NK. Energetic interventions for healthspan and resiliency with aging. Exp Gerontol 2016 May 31 PMC5133182

Milman S, Huffman DM, Barzilai N. The Somatotropic Axis in Human Aging: Framework for the Current State of Knowledge and Future Research. Cell Metab 2016 Jun 14;23(6):980-9 PMCID: PMC4919980

Huffman DM, Justice J, Stout MB, Kirkland JL, Barzilai N, Austad SN. Evaluating Healthspan in Pre-Clinical Models of Aging and Disease: Guidelines, Challenges and Opportunities for Geroscience.  Gerontol A Biol Sci Med Sci 2016 Aug 16 PMC5055649

Gubbi S, Farias Quipildor G, Barzilai N, Huffman DM, Milman S. IGF-1: The Jekyll & Hyde of the aging brain. 2018 J Mol Endocrinol 2018 Jul;61(1):T171-T185. PMC5988994

Gandy S, Huffman DM. Unexpected systemic phenotypes result from focal combined deficiencies of forebrain insulin receptor/IGF-1 receptor signaling. Proc Natl Acad Sci 2019 Mar 11. PMC6442574

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