Sofiya Milman, MD, MSc, enjoys exploring new frontiers. A gerontologist physician-scientist at Montefiore Einstein and Director of Human Longevity Studies at Einstein’s Institute for Aging Research, Dr. Milman studies a unique population of centenarians. “There are a lot of unknowns in the field of aging,” she said. “It’s a new frontier of research.”
Hooked on Aging
An Associate Professor of Medicine (Divisions of Endocrinology and Geriatrics) and Genetics at Einstein and an attending physician in Endocrinology at Montefiore, Dr. Milman was fascinated by physiology and genetics during her college years and at SUNY Stonybrook School of Medicine, from which she received her medical degree in 2006. Following internal medicine residency and fellowship in endocrinology, both at Montefiore, a life-changing opportunity arose to combine her passions for physiology and genetics through work with Nir Barzilai, MD, director of Institute for Aging Research, the Nathan Shock Center of Excellence in the Biology of Aging, and of the Glenn Center for the Biology of Human Aging at Einstein. During her two years of post-doctoral training in translational gerontology and genetics at Einstein’s Institute for Aging Research under Dr. Barzilai’s mentorship, she got hooked on the study of aging and found her life’s work.
“I realized there’s so much we still don’t know about the physiology of aging, especially what happens in the endocrine system,” Dr. Milman recalled recently. Marrying her training in endocrinology and her interest in gerontology would allow her to pursue her passion: contributing to the discovery of new ideas related to physiology and biology and incorporating genetics to see “how our genes actually control our physiology and allow us to age in a healthy way.” To obtain the additional skills she would need to conduct her own research, she enrolled in Einstein’s Clinical Research Training Program and graduated in 2013 and joined the Einstein faculty that same year.
Today, Dr. Milman’s research focuses on a population of Ashkenazi Jewish centenarians and their children who exhibit a group of special traits. Healthy longevity runs in most of these families, suggesting a heritable basis for this phenomenon. Her team conducts translational research aimed at the discovery of genomic mechanisms that regulate endocrine and metabolic pathways that protect against common age-related diseases such as diabetes, cardiovascular disease and Alzheimer's disease.
NIH Support to Study Delays in Aging
Dr. Milman was recently awarded a five-year, $4 million R01 grant from the National Institute on Aging (NIA) to identify genetic variants and their downstream actions that protect certain individuals and their progeny from the effects of aging-- a major risk factor for Alzheimer’s disease and dementia. Evidence shows that diminished signaling via the somatotropic pathway that signals via growth hormone and insulin-like growth factor-1 (GH/IGF-1) delays aging, resulting in longer lifespan and dementia-free survival, in both model organisms and people. Most centenarians have several mutations that weaken somatotropic signaling. Dr. Milman and her colleagues will study participants in Einstein's LonGenity study -- a cohort of 1,400 older adults, half of them the offspring of centenarians -- to identify genes that inhibit growth-related signaling and their downstream effects. The researchers will investigate the role that somatotropic signaling plays in the brains of aging humans. They hope to co-identify mechanisms that confer cognitive resilience by delaying aging. Their findings could lead to therapies to help protect the general elderly population against Alzheimer's and other aging-associated diseases.
“The reason we're interested in this question of IGF-1 and growth hormone is that prior research in model organisms -- from earthworms to fruit flies to rodents -- has demonstrated that decreasing the signaling for this hormone pathway actually leads to longevity and better health in the organism,” Dr. Milman explained.
A Multidisciplinary Approach
The project brings together a multidisciplinary team of experts, including Joe Verghese, MBBS, Division Chief of Geriatrics and director, Jack and Pearl Resnick Gerontology Center and professor of Neurology and Medicine; Zhengdong Zhang, PhD, a computational geneticist and associate professor, Department of Genetics; Fernando Macian-Juan, MD, PhD, professor, Department of Pathology; Helena Blumen, PhD, assistant professor, Department of Medicine (Geriatrics) and The Saul R. Korey Department of Neurology; and Tao Wang, PhD, director, Genetic and Genomics Data Analysis Unit, Division of Biostatics in the Department of Epidemiology and Population Health.
The new study builds upon Dr. Milman’s previous research into the role that GH/IGF-1 play in longevity. Funded by a K23 Beeson Mentored Career Development Award that she received from the NIA in 2015, the four-year study built upon evidence suggesting that gene variants code for proteins that improve health and extend survival by weakening GH/IGF-1 signaling.
Building Upon Research
Dr. Milman and her team are taking a novel approach in the current project. “We're trying to get beyond the levels of IGF-1 that are measured in the blood, because those are affected by many external factors such as diet, age and disease state, and may not give an accurate read,” she explained. “Now, we're not only looking at IGF-1, we're also looking at all of the molecular pathways that are downstream of IGF, ones that are stimulated by IGF-1.” This includes looking at all the genes that regulate that pathway, to get a comprehensive understanding of its function rather than just looking at one piece. The researchers are also looking at the role that autophagy – the process by which a cell maintains homeostasis by removing “garbage” from the cell – plays in delaying aging and neurodegenerative diseases.
Dr. Milman’s research is carried out within the environment of the Longevity Genes Project, a cross-sectional study of centenarians and LonGenity, an independent, longitudinal study of offspring of centenarians, who are enriched with longevity genomes, and age-matched controls without parental history of longevity. Both studies, conceived and led by her mentor, Dr. Barzilai, have garnered worldwide attention for their groundbreaking findings. The overarching hypothesis, supported by observational and genetic evidence, is that unique genomic elements protect against age-related diseases and result in healthy longevity.
A 2014 recipient of the Glenn Award for Research in Biological Mechanisms of Aging, Dr. Milman enjoys the collaborative nature of research. She believes that through team science, the prospect of healthy aging is a tangible reality.
Posted on: Tuesday, May 26, 2020