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Dr. Shoshana Yakar Awarded $2.27 Million to Examine Age-Related Changes in Bone

09/21/2018

NIH-Funded Research Will Shed Light on Molecular Mechanisms Responsible for Bone Loss in Aging

The National Institute of Aging, part of the National Institutes of Health, has awarded a grant to researchers at New York University College of Dentistry (NYU Dentistry) to unravel the distinct and overlapping effects of normal aging and the age-related decrease in growth hormone on bone health. The grant provides nearly $2.27 million to NYU Dentistry over five years.

The world older population (aged 65 and older) is increasing and is projected to rise from 8.5 percent to date to 17 percent of the world population by 2050. In the developing world, chronic diseases are the main causes of mortality and morbidity in old age. With the increase in the elderly population we expect to see more people with senile osteoporosis (age-induced bone loss) and fractured hips. Increases in primary or secondary prevention efforts are expected to have a significant impact on skeletal health in older age.

Age-induced changes in bone are thought to result from two causes: somatopause, the age-related decline in growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and normal changes in bone cell activity and tissue properties. The processes are overlapping, but their distinct effects on bone loss have not yet been established.

GH and IGF-1 are key endocrine factors regulating body composition (lean and fat mass), acquiring bone mass, and maintaining bone mineral density (BMD) during adulthood and aging. Somatopause has been considered a significant cause for changes in body composition, BMD, as well as increased morbidity and mortality. Strategies to increase GH and IGF-1 in bone tissue during aging are expected to improve bone quality, which would have a profound economic impact by decreasing the healthcare costs of age-related bone disease.

"Developing new approaches to combat age-induced bone loss and bone fragility requires basic understanding of the molecular mechanisms responsible for bone cells dysfunction. Our research will help us to better understand the effect of somatopause on the viability and function of osteocytes, the most abundant bone cells," said Shoshana Yakar, PhD, associate professor of basic science and craniofacial biology at NYU Dentistry and the study's principal investigator.

The NIH-funded research builds on a long-standing collaboration between Yakar, an expert in growth hormone and IGF-1 physiology; Mitchell Schaffler, PhD, of City College, City University of New York, an expert in osteocytes and bone biomechanics; and NYU Dentistry’s Evgeny Pavlov, PhD, an expert in mitochondria.

Together, the researchers will study the bone integrity of mice in order to determine the mechanisms by which changes in GH and IGF-1 affect osteocytes of aging bones.

"Our research links three hallmarks of aging: altered intercellular communication, which is central to tissue integrity; mitochondrial dysfunction, which is central to cell survival; and deregulated nutrient sensing, which is central to cellular metabolism," said Yakar.

Findings from their studies will provide a global view of how osteocytes respond to somatopause and normal aging, highlight new potential target genes that play roles in response to stress, and provide a roadmap to develop strategies to prevent or delay bone loss during aging.

The research is supported by the National Institute of Aging under award number R01AG056397.