Abstract Geroscience research benefits from interdisciplinary approaches, team science, and collaborations, which collectively facilitate the discovery of aging mechanisms and their translation into tangible, clinical interventions. Since its inception in 2019, the Midwest Aging Consortium (MAC) has provided an engaging platform for aging researchers in the United States’ Midwest to connect, collaborate, and exchange ideas. The Sixth Annual Research Symposium of the MAC held at the Mayo Clinic in Rochester, Minnesota, in April 2025 highlighted the continued impact of the MAC in bringing together aging researchers, including many trainees and early career investigators, into a collaborative environment. This record-setting event featured interdisciplinary research on key aging mechanisms, including lipid metabolism, mitochondrial dysfunction, stress response, cellular senescence, and immune adaptations across organ systems. New therapeutic concepts and clinical trial approaches were presented. Cutting-edge methodologies including single-cell and spatial transcriptomics, metabolomics, and organoid cultures, to dissect aging process in tissue-specific and systemic contexts also were presented. Overall, the MAC symposium underscored the translational potential of geroscience and reinforced the MAC’s mission to accelerate aging research through regional collaborations and innovation.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Objective In contrast to intentionally restricting energy intake, restricting the eating window may be an option for treating obesity. By comparing time‐restricted eating (TRE) with an unrestricted (non‐TRE) control, it was hypothesized that TRE facilitates weight loss, alters body composition, and improves metabolic measures. Methods Participants (17 women and 3 men; mean [SD]: 45.5 [12.1] years; BMI 34.1 [7.5] kg/m 2 ) with a prolonged eating window (15.4 [0.9] hours) were randomized to TRE ( n = 11: 8‐hour window, unrestricted eating within window) versus non‐TRE ( n = 9: unrestricted eating) for 12 weeks. Weight, body composition (dual x‐ray absorptiometry), lipids, blood pressure, 2‐hour oral glucose tolerance, 2‐week continuous glucose monitoring, and 2‐week physical activity (actigraphy assessed) were measured during the pre‐ and end‐intervention periods. Results The TRE group significantly reduced the eating window (end‐intervention window: 9.9 [2.0] hours) compared with the non‐TRE group (end‐intervention window: 15.1 [1.1] hours) ( P < 0.01). Compared with non‐TRE, TRE decreased the number of eating occasions, weight, lean mass, and visceral fat (all P ≤ 0.05). Compared with preintervention measures, the TRE group reduced the number of eating occasions (−21.9% [30.1%]) and reduced weight (−3.7% [1.8%]), fat mass (−4% [2.9%]), lean mass (−3.0% [2.7%]), and visceral fat (−11.1% [13.4%]) (all P ≤ 0.05). Physical activity and metabolic measures remained unchanged. Conclusions In the setting of a randomized trial, TRE presents a simplified view of food intake that reduces weight.
Training status diverges muscle diacylglycerol accumulation during free fatty acid elevation
How endurance training alters muscle lipid metabolism while preserving insulin sensitivity remains unclear. Because acute free fatty acid (FFA) elevation by lipid infusion reduces insulin sensitivity, we hypothesized that training status would alter accumulation of muscle triacylglycerol (TAG), diacylglycerol (DAG), ceramide, and acylcarnitine during acute FFA elevation. Trained ( n = 15) and sedentary ( n = 13) participants matched for age, sex, and BMI received either a 6-h infusion of lipid (20% Intralipid at 90 ml/h) or glycerol (2.25 g/100 ml at 90 ml/h) during a hyperinsulinemic euglycemic clamp. Muscle biopsies were taken at 0, 120, and 360 min after infusion initiation to measure intramyocellular concentrations of TAG, DAG, ceramides, and acylcarnitines by liquid chromatography-tandem mass spectrometry. Trained participants had a higher V̇o2 maxand insulin sensitivity than sedentary participants. The lipid infusion produced a comparable elevation of FFA (594 ± 90 μmol/l in trained, 721 ± 30 μmol/l in sedentary, P = 0.4) and a decline in insulin sensitivity (−44.7% trained vs. −47.2% sedentary, P = 0.89). In both groups, lipid infusion increased the linoleic and linolenic acid content of TAG without changing total TAG. In the sedentary group, lipid infusion increased total, oleic, and linoleic acid and linolenic acid content of DAG. Regardless of training status, lipid infusion did not alter total ceramide, saturated ceramide, palmitoyl-carnitine, or oleoyl-carnitine. We conclude that during acute FFA elevation, trained adults have a similar decline in insulin sensitivity with less accumulation of muscle DAG than sedentary adults, suggesting that lipid-induced insulin resistance can occur without elevation of total muscle DAG.
Acute Free Fatty Acid Elevation Eliminates Endurance Training Effect on Insulin Sensitivity
AbstractContext:Both training and normal body mass index are associated with high insulin sensitivity, but the mechanism may be different.Objective:The aim of the study was to examine whether lean trained humans may be protected from acute free fatty acid (FFA)-induced insulin resistance compared with lean sedentary humans.Design and Setting:We conducted an interventional trial using either a 6-h lipid (20% Intralipid at 90 ml/h) or glycerol (2.25 g/100 ml at 90 ml/h) infusion along with a concurrent hyperinsulinemic-euglycemic clamp and serial muscle biopsies (0, 120, 360 min) at a clinical research unit at the University of Minnesota.Patients or Participants:The study included lean endurance-trained (n = 14) and sedentary (n = 14) individuals matched for age, gender, and body mass index.Main Outcome Measures:We measured the decline in glucose infusion rate (GIR) during the hyperinsulinemic-euglycemic clamp.Results:The trained group had higher baseline mitochondrial DNA copy number, mRNA of cytochrome C oxidase subunit 3, and insulin sensitivity (as measured by GIR) compared with the sedentary group. When FFA was acutely elevated to the upper physiological range (0.6–0.7 mEq/liter) by lipid infusion, the GIR in both activity groups declined similarly compared with their respective glycerol controls, although insulin signaling, as measured by Ser 473 pAKT/AKT, remained comparable. Specific to the trained group, the stimulatory effect of hyperinsulinemia on mitochondrial mRNA levels during the glycerol infusion was absent during the lipid infusion.Conclusions:Elevated FFA had similar effects in reducing insulin sensitivity in trained and sedentary humans. In trained participants, this decline was associated with alterations in the skeletal muscle mitochondrial mRNA response to hyperinsulinemia.