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  11th International Workshop
on HIV and Aging
30 September - 2 October 2020
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Urine mtDNA Signals Lower Muscle, Fat
Mass, Weight in Older Group With HIV

  11th International Workshop on HIV & Aging Virtual Meeting, September 30 to October 2, 2020
By Mark Mascolini for NATAP and Virology Education
Cell-free urine mitochondrial DNA (cfmtDNA) correlated with lower skeletal muscle, lower fat mass, and unintentional weight loss (a frailty marker) in a study of 164 HIV-positive people averaging 61 years in age [1]. Weill Cornell Medicine researchers who conducted this study believe cfmtDNA--available from urine samples--merits further scrutiny as a marker of geriatric syndromes in people with HIV.
The Weill Cornell team in New York City noted that aging people with HIV have higher rates of geriatric conditions like frailty, falls, and sarcopenia (age-related muscle loss) than their age peers without HIV. Ongoing inflammation despite suppressive antiretroviral therapy, these researchers proposed, may be a component of muscle loss and developing frailty. Released from cells during cell death, cfmtDNA, they added, may be both a mediator and a marker of upset inflammatory processes.
To explore these issues, they conducted a cross-sectional study of HIV-positive people 55 or older tested for Fried frailty phenotype [2], skeletal muscle and fat mass, waist circumference, urine albumin, urine creatinine, cfmtDNA (by qPCR), and other conditions and lab markers. The researchers had urine samples for 151 of 164 people.
The 164 cohort members averaged 61 years in age (range 55 to 78), 34% were women, half were African American, and 93% had an HIV load below 200 copies. The group had been diagnosed with HIV for a median of 25 years (range 5 to 38), and median CD4 count stood at 582 (interquartile range 402 to 795).
Geometric mean cfmtDNA stood at 2.4 x 10(8) copies/gram of urine creatinine (95% confidence interval 2.0 to 3.1 x 10(8)). Linear regression adjusted for sex, diabetes diagnosis, microalbuminuria, and use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) identified links between higher cfmtDNA and both elevated microalbuminuria (P < 0.001) and older age (P = 0.01). (Microalbuminuria, defined as urine creatinine above 30 mg/gram of urine, signals abnormal albumin excretion in urine, which may indicate endothelial dysfunction and higher heart disease risk.) Variables not linked to cfmtDNA in this analysis were sex (P = 0.16), diabetes, and use of ACEi or ARB.
Linear regression adjusted for age, sex, and elevated microalbuminuria determined inverse relationships between cfmtDNA and both skeletal muscle index (beta = -0.19, P < 0.01) and fat mass index (beta = -0.08, P = 0.02).
Among the 164 study participants, 20 (12%) were frail (met 3, 4, or 5 frailty criteria[2]), 95 (58%) were prefrail (met 1 or 2 frailty criteria), and 49 (30%) were not frail. People with the frailty marker unintentional weight loss had significantly higher average cfmtDNA (P = 0.03). But cfmtDNA level was not tied to the other frailty components--gait speed, grip strength, exhaustion, and low physical activity.
Thirty-six people (22% of 164) fell in the past 6 months. Chi(2) test linked falls to more advanced frailty state (P = 0.04). Logistic regression analysis saw no association between cfmtDNA and falls, and chi(2) test did not link falls to unintentional weight loss. Logistic regression discerned no correlation between recent falls and skeletal muscle index or fat mass index.
Overall findings led the authors to propose that “urine cfmtDNA may be a novel biomarker in assessing geriatric syndrome in older people with HIV.” High cfmtDNA, they summarized, was linked to lower skeletal muscle, lower fat mass, unintentional weight loss, older age, and higher microalbuminuria. But cfmtDNA was not linked to falls in this analysis.
1. Johnston C, Choi M, Derry H, et al. Cell-free urine mitochondrial DNA as a marker of aging-related phenotypes in older people living with HIV. 11th International Workshop on HIV & Aging Virtual Meeting, September 30 to October 2, 2020. Abstract 10.
2. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-56. doi: 10.1093/gerona/56.3.m146.