Innate immunity and the immunology of infection in older adults

It is estimated that 55.7 million Americans were age 65 and older in 2020, a proportion of the population that has been growing with the aging of the post-World War II “baby boom” generation (1946-1964); by 2040 this number is projected to be 80.8 million, with those age 85 and older projected to increase from 6.7 to 14.4 million during this period. In addition, over half of the population living with HIV infection in the US is over age 50, a proportion expected to increase to over 70% by 2030. An additional challenge is the growing number of adults over age 65 waiting for solid organ transplant; this proportion has been growing steadily and is currently nearly a quarter of all patients on the waitlist. Older adults have substantially increased risks for morbidity and mortality from infectious diseases ranging from urinary tract infections, pneumonia, tuberculosis, sepsis and other conditions, and also show generally decreased immune responses to vaccination. Aging of the population represents a challenge to the practice of infectious diseases, as illustrated most recently by the devastating impact of COVID-19 in older adults—especially prior to vaccine availability. Understanding the interface of the biology of aging with infectious diseases such as HIV and vaccine response is the research focus of faculty in the Section of Infectious Diseases

1. To conduct high-impact research at the interface of age and associated medical conditions such as HIV to identify mechanisms underlying impaired immune responses to vaccination or infection.
2. To promote the development of interventions aimed at enhancing immune responses in older adults.
3. To support and nurture the development of investigators who will advance basic and translational research on aging and infectious diseases

Our faculty are engaged in rigorous programs funded by the NIH and other foundations to understand the molecular mechanisms leading to impairments in immune response in the context of age and co-morbid conditions such as HIV. We study immune responses in the context of infectious diseases such as COVID-19 as well as responses to vaccination (such as to seasonal influenza and SARS-CoV-2). We utilize tools of molecular immunology and computational biology, including state-of-the-art methods in single-cell gene expression and spatial transcriptomics in this work, which focuses on human immunology and has a particular interest in age-associated alterations in innate immune responses and chronic inflammation.

Second-year fellows in Infectious Diseases can choose a research focus in the study of the immune system and Aging. Our faculty are also part of Y-Age, the Yale Center for Research on Aging—an interdisciplinary research program in Geroscience and the Biology of Aging—and have close collaborations with the Yale Claude D. Pepper Older Americans Independence Center, a center funded by the National Institute on Aging supporting translational research on aging that offers research grant and career development resources for new investigators. Dr. Shaw also organizes a monthly Biology of Aging seminar series with invited speakers from inside and outside Yale.