Dr. Sofiya Milman is Professor of Medicine and of Genetics, Interim Vice-Chair for Research in the Department of Medicine, and Director of Human Longevity Studies at Einstein’s Institute for Aging Research. Dr. Milman’s research focuses on a unique population of centenarians and their families who are generally free of age-related diseases. Healthy longevity runs in most of these families, suggesting a heritable basis for this phenomenon. Dr. Milman's team conducts translational research focused on the discovery of genomic mechanisms that regulate endocrine and metabolic pathways that protect against common age-related diseases, like diabetes, cardiovascular disease and Alzheimer's. 

Many of the discovered longevity genes and phenotypes are related to hormonal pathways. Changes in most hormones are observed throughout the human lifespan, but it remains unknown whether the observed changes cause aging, are associated with age but are not the cause of aging, or are protective for the aging body. Identification of protective endocrine parameters will inform our understanding of the mechanisms of healthy aging and lead to the discovery of interventions that protect from age-related diseases.

A biological pathway that has been repeatedly implicated in aging is the somatotropic axis that involves signaling via growth hormone and insulin-like growth factor-I (IGF-I).  Substantial evidence exists that diminished signaling via this pathway delays aging, resulting in longer lifespan and health-span, not only in animal models, but also in humans. In fact, Dr. Milman's research demonstrated that lower IGF-I levels were associated with longer survival and better cognition in humans with exceptional longevity and provided evidence against supplementing older adults with growth hormone in an attempt to delay aging. Dr. Milman's team uses computational approaches to integrade genetic information, such as whole-exome sequencing, with rich phenotype data in families with inherited longevity to understand the genetic and molecular mechanisms that lead to protective effects of low IGF-I. 

     1. Zhang WB, Ye K, Barzilai N, Milman S. The antagonistic pleiotropy of insulin-like growth factor 1. Aging Cell 2021; 20(9), e13443; PMCID: PMC8441393 

     2. DeVito LM, Barzilai N, Cuervo AM, Niedernhofer LJ, Milman S, Levine M, Promislow D, Ferrucci L, Kuchel GA, Mannick J, Justice J, Gonzales MM, Kirkland JL, Cohen P, Campisi J. Extending human healthspan and longevity: a symposium report. Ann NY Acad Sci 2021

     3. Zhang WB, Aleksic S, Gao T, Weiss EF, Demetriou E, Verghese J, Holtzer R, Barzilai N, Milman S. Insulin-like Growth Factor-1 and IGF Binding Proteins Predict All-Cause Mortality and Morbidity in Older Adults. Cells 2020; 9(6):E1368, PMCID:PMC7349399

     4. Zhang ZD, Milman S, Lin J, Barzilai N, Gorbunova V, Ladiges WC, Niedernhofer LF, Suh Y, Robbins PD, Vijg J. Genetics of extreme human longevity to guide drug discovery for healthy ageing. Nat Metab 2020; 2(8)663-672.

     5. Lehallier B, Gate D, Schaum N, Nanasi T, Lee SE, Yousef H, Moran Losada P, Berdnik D, Keller A, Verghese J, Sathyan S, Franceschi C, Milman S, Barzilai N, Wyss-Coray T. Undulating changes in human plasma proteome profiles across the lifespan. Nat Med 2019; 25(12):1843-1850; PMCID: PMC7062043

     6. Gubbi S, Quipildor GF, Barzilai N, Huffman DM, Milman S. 40 Years of IGF-1: IGF-1: the Jekyll and Hyde of the aging brain. J Mol Endocrinol 2018; 61(1):T171-T185. PMCID: PMC5988994

     7. Gubbi S, Schwartz E, Crandall JP, Verghese J, Holtzer R, Atzmon G, Braunstein R, Barzilai N, Milman S. Effect of Exceptional Parental Longevity and Lifestyle Factors on Prevalence of Cardiovascular Disease in Offspring. Am J Cardiol 2017

     8. Ismail K, Nussbaum L, Sebastiani P, Andersen S, Perls T, Barzilai N, Milman S. Compression of Morbidity is Observed Across Cohorts with Exceptional Longevity. J Am Geriatr Soc 2016; 64(8):1583-91. PMCID: PMC4988893

    9. 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; 23(6):980-9. PMCID: PMC4919980

    10. Perice L, Barzilai N, Verghese J, Weiss EF, Holtzer R, Cohen P, Milman S. Lower Circulating Insulin-like Growth Factor-I is Associated with Better Cognition in Females with Exceptional Longevity Without Compromise to Muscle Mass and Function. Aging Albany NY) 2016; 8(10): 2414-2424. PMCID: PMC5115897

    11. Milman S, Barzilai N. Dissecting the Mechanisms Underlying Unusually Successful Human Health Span and Life Span. Cold Spring Harb Perspect Med 2015 Dec 4. PMCID: PMC4691799 

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