Jurivich, Donald A.

Abstract Foxp3⁺ regulatory T cells (Tregs) maintain immune homeostasis, yet the process that preserves their stability during aging remain unclear. Mechanistic progress has been hindered by models that ablate Tregs or delete Foxp3 , which induce acute autoimmunity and prevent longitudinal study of physiological regulatory drift. Here, we establish a dose-dependent mitochondrial framework that preserves Treg lineage survival while permitting gradual metabolic attenuation. Using Treg-restricted TFAM modulation, a complementary haploinsufficient model, and whole-spleen single-cell profiling. We identify lineage-selective immune remodeling characterized by contraction of naïve CD8⁺ and follicular B-cell pools, alteration of CD4⁺ states, expansion of activated Tregs, and emergence of neuroimmune stress linked transcriptional modules that parallel physiological aging. Mechanistically, mitochondrial insufficiency is associated with functional loss of FOXP3- centered chromatin coordination and enrichment of NF-κB/NFAT/AP-1 inflammatory and senescence programs while lineage identity remains detectable. Partial mitochondrial attenuation within Tregs alone is sufficient to drive chronic low-grade systemic inflammation, neuromuscular decline, gut microbial restructuring, and elevated microglial responsiveness without Treg depletion. Pharmacologic and microbiota-directed interventions partially reduce inflammatory tone and improve functional metrics. Together, our findings identify TFAM as a key regulator of immune aging and reveal that healthy mitochondrial function in Tregs is essential for protecting against inflammaging and age-associated functional decline.

Abstract The pandemic has challenged training programs in numerous ways, specifically in the ability to conduct group based teaching sessions. To overcome this challenge Twitter was examined as a vehicle for engaging Geriatric Fellows in education about critical appraisal of clinical research. A secondary objective was to develop educational synergy among university-based programs. To achieve these aims, 5 Midwestern Geriatric and Palliative Medicine Fellowship programs agreed to enroll their fellows into a monthly Geriatrics Twitter Journal Club, that commences on Twitter Tuesday and lasts a week. Each month, an assigned fellow selects an article to discuss and creates a short video to introduce it. A Twitter meister deliveres structured questions to guide fellows’ collective input on the article being critiqued. Over a 3 month roll out of @GeriatricJC, the twitter account of the journal club has gained 144 followers that includes 20 fellows, 63 geriatricians/geriatric faculty, 28 organizational accounts, 5 students and around 28 other providers and experts. From December 2020- February 2021, account generated tweets resulted in an average of 397 impressions/day with 2548 visits to the account profile per month. Videos posted have averaged 73 views/video. Discussion in journal club using #GeriJC has garnered 178 tweets from participants. This project shows that Twitter is a feasible platform for a fellowship journal club among several training programs, thus expanding expertise in evidence-based medicine while lowering the administrative burden of preparing journal club within a single program and increasing both faculty and trainee convenience of learning.