Novel approaches to address cognitive aging and to delay or prevent cognitive decline in older individuals will require a better understanding of the biological and environmental factors that contribute to it. Studies in animal models-in particular, animals whose cognitive trajectory across their life span closely tracks that of humans-can provide important insights into the factors that contribute to the accumulation of reserve and ways in which it is preserved or depleted. A better understanding of the molecular processes that underlie these elements would enhance and guide not only research but also treatment approaches to these issues. These treatment approaches may include noninvasive brain stimulation and drug treatments to promote youthfulness or combat the aging process. It is important to realize, however, that these processes occur in the context of the human experience, and studies of them must consider the complexity and individuality of each person's life.

OBJECTIVE: To examine associations between frailty and drug, alcohol, and tobacco use among a large diverse cohort of people with HIV (PWH) in clinical care in the current era. METHODS: PWH at 7 sites across the United States completed clinical assessments of patient-reported measures and outcomes between 2016 and 2019 as part of routine care including drug and alcohol use, smoking, and other domains. Frailty was assessed using 4 of the 5 components of the Fried frailty phenotype and PWH were categorized as not frail, pre-frail, or frail. Associations of substance use with frailty were assessed with multivariate Poisson regression. RESULTS: Among 9336 PWH, 43% were not frail, 44% were prefrail, and 13% were frail. Frailty was more prevalent among women, older PWH, and those reporting current use of drugs or cigarettes. Current methamphetamine use (1.26: 95% CI 1.07-1.48), current (1.65: 95% CI 1.39-1.97) and former (1.21:95% CI 1.06-1.36) illicit opioid use, and former cocaine/crack use (1.17: 95% CI 1.01-1.35) were associated with greater risk of being frail in adjusted analyses. Current smoking was associated with a 61% higher risk of being frail vs. not frail (1.61: 95% CI 1.41-1.85) in adjusted analyses. CONCLUSIONS: We found a high prevalence of prefrailty and frailty among a nationally distributed cohort of PWH in care. This study identified distinct risk factors that may be associated with frailty among PWH, many of which, such as cigarette smoking and drug use, are potentially modifiable.

It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging.