Connecting aging biology and inflammation in the omics era

Aging is characterized by the accumulation of damage to macromolecules and cell architecture that triggers a proinflammatory state in blood and solid tissues, termed inflammaging. Inflammaging has been implicated in the pathogenesis of many age-associated chronic diseases as well as loss of physical and cognitive function. The search for mechanisms that underlie inflammaging focused initially on the hallmarks of aging, but it is rapidly expanding in multiple directions. Here, we discuss the threads connecting cellular senescence and mitochondrial dysfunction to impaired mitophagy and DNA damage, which may act as a hub for inflammaging. We explore the emerging multi-omics efforts that aspire to define the complexity of inflammaging - and identify molecular signatures and novel targets for interventions aimed at counteracting excessive inflammation and its deleterious consequences while preserving the physiological immune response. Finally, we review the emerging evidence that inflammation is involved in brain aging and neurodegenerative diseases. Our goal is to broaden the research agenda for inflammaging with an eye on new therapeutic opportunities.

Multidomain cognitive dysfunction after minor stroke suggests generalized disruption of cognitive networks.

OBJECTIVE: Although small strokes typically result in "good" functional outcomes, significant cognitive impairment can occur. This longitudinal study examined a cohort of patients with minor stroke to determine the pattern of deficits, evolution over time, and factors associated with outcome. METHODS: Patients admitted to the hospital with their first clinical minor stroke (NIH Stroke Scale [NIHSS] ≤ 10, absence of severe hemiparesis, aphasia, or neglect) were assessed at 1 month post-infarct, and a subset were followed over time (with 6- and 12-month evaluations). Composite scores at each time point were generated for global cognition, verbal memory, spatial memory, motor speed, processing speed, and executive function. Paired t-tests evaluated change in scores over time. Regression models identified factors associated with initial performance and better recovery. RESULTS: Eighty patients were enrolled, evaluated at 1 month, and prospectively followed. The average age of the participants was 62.3 years, and mean education was 13.5 years. The average stroke volume was 6.6 cc; mean NIHSS score was 2.8. At 1 month, cognitive scores were below the normative range and > 1 standard deviation below the patient's peak ("recovery") score for every cognitive domain, strongly suggesting that they were well below patients' prestroke baselines. Forty-eight patients followed up at 6 months, and 39 at 12 months. Nearly all (98%) patients significantly improved in global cognition (averaged across domains) between 1 and 6 months. Between 6 and 12 months, recovery was variable. Higher education, occupational class, and Caucasian race were associated with higher recovery scores for most domains. CONCLUSIONS: Cognitive impairment across multiple domains is common following minor stroke regardless of infarct location, suggesting a global process such as network dysfunction that improves over 6 months. Degree of recovery can be predicted using baseline factors.