Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Kyoko Konishi, PhD

Massachusetts General Hospital


Telomere length (TL) is an important cellular marker of biological aging, impacting the brain and heart. Shorter TL is associated with cognitive decline, increased risk of hypertension and dementia, and atrophy in the hippocampus, a key region in the memory circuitry. Telomerase, a ribonucleoprotein that repairs telomere shortening, is regulated by 17β-estradiol, a sex steroid hormone that declines in menopause. Here, we assessed the impact of leukocyte TL, in relation to sex, reproductive aging, and adult hypertension, on memory circuitry regional brain volumes and memory performance in early midlife. Participants (N=212; 106 females, 106 males; ages 45–55) underwent MRI and neuropsychological assessments of verbal, associative, and working memory. In women, we found that longer TL was associated with better verbal memory (β=0.66, pFDR=0.03). We also found a significant interaction between menopausal status and TL in associative memory (pFDR =0.04). Only in postmenopausal women, longer TL was related to better associative memory (β=0.36, pFDR =0.05) and larger volume in the right hippocampus (β=111.92, pFDR =0.04). In men, longer TL tended to be associated with larger volume in the parahippocampal cortex (β=127.86, pFDR =0.08) and anterior cingulate cortex (β=271.64, pFDR =0.08). Finally, we found shorter TL was associated with hypertension in midlife (β=-0.41, p=0.007), which in turn was related to poor working memory in men (β=-1.85, p=0.0006) and women (β=-1.84, p=0.005) and poor associative memory in women (β=-0.73, p=0.005). Results demonstrated that longer TL is associated with better memory function and larger volume in memory circuitry regions in early midlife, an effect that differs by sex/reproductive status. Further, results suggest that TL may partially mediate the relationship between cardiovascular health and cognitive function in later life. Taken together, TL may serve as an early biomarker of sex-dependent brain and cardiovascular abnormalities in early midlife.


3PM – Welcome Remarks
3:05PM – Keynote Address
3:45PM – Featured Short Talks
4:20PM – Lightning Talks
4:50PM – Closing Remarks

Keynote Speaker

Janine Austin Clayton, MD

Janine Austin Clayton, M.D., Associate Director for Research on Women’s Health and Director of the Office of Research on Women’s Health (ORWH) at the National Institutes of Health (NIH), is the architect of the NIH policy requiring scientists to consider sex as a biological variable across the research spectrum. This policy is part of NIH’s initiative to enhance reproducibility through rigor and transparency. As co-chair of the NIH Working Group on Women in Biomedical Careers with NIH Director Dr. Francis Collins, Dr. Clayton also leads NIH’s efforts to advance women in science careers.

Prior to joining the ORWH, Dr. Clayton was the Deputy Clinical Director of the National Eye Institute (NEI) for seven years. A board-certified ophthalmologist, Dr. Clayton’s research interests include autoimmune ocular diseases and the role of sex and gender in health and disease. She is the author of more than 120 scientific publications, journal articles, and book chapters.
Dr. Clayton, a native Washingtonian, received her undergraduate degree with honors from Johns Hopkins University and her medical degree from Howard University College of Medicine. She completed a residency in ophthalmology at the Medical College of Virginia. Dr. Clayton completed fellowship training in cornea and external disease at the Wilmer Eye Institute at Johns Hopkins Hospital and in uveitis and ocular immunology at NEI.

Dr. Clayton has received numerous awards, including the Senior Achievement Award from the Board of Trustees of the American Academy of Ophthalmology in 2008 and the European Uveitis Patient Interest Association Clinical Uveitis Research Award in 2010. She was selected as a 2010 Silver Fellow by the Association for Research in Vision and Ophthalmology. In 2015, she was awarded the American Medical Women’s Association Lila A. Wallis Women’s Health Award and the Wenger Award for Excellence in Public Service. Dr. Clayton was granted the Bernadine Healy Award for Visionary Leadership in Women’s Health in 2016. She was also selected as an honoree for the Woman’s Day Red Dress Awards and the American Medical Association’s Dr. Nathan Davis Awards for Outstanding Government Service in 2017.