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New supplemental award examines mitochondrial function and frailty development among people with and without HIV

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Frailty Science Team

Frailty Science Team

MitochondriaThe Johns Hopkins Older Americans Independence Center (OAIC), a long-running NIH funded research program focused on frailty research, was recently awarded a supplemental grant to investigate the intersecting biological pathways that drive early onset of physical frailty in a subset of individuals living with and without HIV through the study of mitochondrial decline. Among people with HIV (PWH), frailty predicts mortality, comorbidities, and hospitalization, and is an important indicator of quality of life. The underlying mechanisms for frailty development are likely multifaceted, due in part to features of biological aging such as mitochondrial decline and chronic inflammation. A major driver of the aging process in PWH is mitochondrial damage, resulting from chronic HIV infection, chronic inflammation, and the effects of some antiretroviral therapies. However, the role of changes in mitochondrial function in the etiology of frailty among PWH remains unclear. Furthermore, each immune cell type may develop different metabolic adaptations in response to stress. The interplay between mitochondrial function and immune activation and senescence in the etiology of frailty development remains unclear.

Dr. Jing Sun is an Assistant Scientist with the Johns Hopkins Bloomberg School of Public Health in Infectious Disease Epidemiology. Dr. Sun is affiliated with:

Dr. Jing Sun

This supplemental award, led by Dr. Jing Sun (Epidemiology), with mentors and colleagues including Drs. Todd Brown (Endocrinology), Dan Arking (Genetic Medicine), Joseph Margolick (Molecular Microbiology and Immunology), Gregory Kirk (Infectious Disease Medicine), and Jeremy Walston (Geriatric Medicine), will evaluate the association of immune cell type-specific mitochondrial function measurements, including mitochondrial content, membrane potential, and superoxide, with HIV infection and frailty by leveraging longitudinal data, specimens, and infrastructure from two established HIV cohorts: 1) the AIDS Linked to the IntraVenous Experience cohort; and 2) the Multicenter AIDS Cohort Study. These cohorts uniquely include PWH and comparable HIV uninfected adults.

Dr. Sun and the research team will pursue the following aims to accomplish these goals: (1) to characterize immune cell activation and senescence and cell type- specific mitochondrial function, stratified by HIV infection status; and (2) to assess the association between cell type-specific mitochondrial function and frailty during longitudinal follow-up among people with and without HIV. They will apply a novel machine learning approach to characterize the complex and high-dimensional biomarker data in immune aging and mitochondrial function to achieve these aims.  With expertise and resources from the OAIC, the current study will provide new understanding of the interplay between HIV infection, immune aging, and mitochondrial function in the etiology of frailty.

More information is available here: https://reporter.nih.gov/search/47Y0OHlInkKj9BQeZ-vlZQ/project-details/10614117

For World AIDS Day, December 1st: How does one face aging when they never planned to survive? 

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Jason Farley PhD, MPH, ANP-BC, FAAN, FAANP, AACRN

Jason Farley PhD, MPH, ANP-BC, FAAN, FAANP, AACRN

Endowed Professor of Nursing Leadership and Innovation Director | Center for Infectious Disease and Nursing Innovation Johns Hopkins University School of Nursing Faculty Profile

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The average age of people living with HIV in most care settings in the United States is 50 years of age or older. For many in this group, a diagnosis of HIV may have occurred decades ago and was accompanied, at the time, with the almost certain fate of disability and eventual death.

This led to people living for the day with no ability to contemplate tomorrow, much less, aging with the virus for decades. Living with the clinical consequences of HIV mono therapy and the subsequent resistance to antiretroviral therapy as well as the significant toxicities associated with these older therapies is a double-edged sword.  On the one hand, their lives were saved, and on the other, quality of life and wellness during the aging process were often sacrificed.

This past week, I had the opportunity at the Association of Nurses and AIDS Care Conference to listen to our elders from across the US who are living and aging with HIV. They wanted us to know that while they’re so happy to be alive they often feel that we as a clinical community have been slow to respond to their voices. Not only do many continue to feel isolated because they’ve lost their formative friend group, but some also reported struggling to make new friends as they continued to live.  Social isolation and loneliness heighten the negative impacts of aging through both biological and psychosocial mechanisms. These conditions enhance frailty (see: HIV and Frailty) and likely contribute to earlier transition to long-term care facilities.

Leaving one’s home and transitioning to long-term care is stressful for anyone.  The fear and anxiety of losing autonomy is coupled with concerns of losing dignity from receiving care, meals, and baths from strangers.  This already challenging situation is made worse when living with HIV.  First, the concern of needing to hide your HIV status and the potential for stigma and discrimination by both healthcare workers and other seniors is very real.  Second, long term care facilities are often ill equipped to manage HIV treatment.  Finally, members of the LGBTQ+ community with HIV suffer the potential need to go back into the closet to avoid further discrimination associated with sexual orientation.

There is hope for change, however.  The community aging with HIV is an active group of seniors who are advocating for change around the world.  Here in Baltimore, “Older Women Embracing Life” was founded in 2005 by women living and aging with HIV out of a premise that emotional support enhances quality of life and reduces psychological stress for people with HIV.  Another group called, “Let’s KickASS,” which stands for AIDS Survivor Syndrome, was founded in 2013 by long-term HIV survivors in San Francisco. Both not-for-profit agencies are pillars of the HIV and aging community.  They support members, patients, care givers, long-term care facilities, and others by increasing awareness of the complex nature of HIV and aging.  Their advocacy is essential to highlighting the community’s voice and we must listen.

Researchers focused on aging also have the opportunity to consider people with HIV in their programs.  For example, a program known as Community Aging in Place or CAPABLE, developed by the Johns Hopkins School of Nursing Professor and now Dean of the School of Nursing, Dr. Sarah Szanton, is transforming aging successfully at home. CAPABLE was designed for low-income seniors to improve safe aging in place.  The approach includes a nurse, an occupational therapist, and a handy worker to address both the home environment and uses the strengths of the older adult to improve safety and independence.  This program is now endorsed by the Center for Medicare.  The original work included only a handful of people with HIV and now collaborations are underway to consider the development of CAPABLE-HIV.  This work will focus on how to adapt CAPABLE for people with HIV and determine the unique needs for safe aging in place for this community.  While in the formative stages, we believe this effort will contribute to national efforts to improve aging in place for people with HIV.  The newly formed Center for Infectious Disease and Nursing Innovation (CIDNI) and the long-standing Center for Innovative Care in Aging are partnering to move this effort forward.  Keep watching this space for opportunities to participate in community advisory board discussions.