A progressive decline in mitochondrial oxidative phosphorylation (OxPhos) is a fundamental feature of aging and a strong predictor of mobility loss, cognitive decline, and dementia. (1-4) Work from the Baltimore Longitudinal Study of Aging and complementary cohorts demonstrates that reduced skeletal muscle mitochondrial OxPhos, assessed in vivo by ^31P-MRS, precedes and predicts deterioration in walking performance, cardiorespiratory fitness, brain structural integrity, and risk of mild cognitive impairment and dementia. These associations suggest that mitochondrial dysfunction represents a shared biological mechanism underlying both physical and cognitive aging. This project focuses on cardiolipin, a signature phospholipid of the mitochondrial inner membrane that is essential for respiratory chain supercomplex assembly, proton handling, and efficient ATP synthesis. Cardiolipin is highly susceptible to oxidative damage, and emerging evidence indicates that oxidized cardiolipin is poorly repaired, promotes inflammation and apoptosis, and compromises mitochondrial quality control. We hypothesize that aging is characterized by the accumulation of oxidized cardiolipin due to impaired remodeling and insufficient availability of key lipid precursors, particularly lysophosphatidylcholine species containing oleic (18:1) and linoleic (18:2) acids. To test this hypothesis, we integrate longitudinal human phenotyping with advanced metabolomics, lipidomics, and “in vivo” imaging. We have identified lipid metabolites linking mitochondrial OxPhos to mobility and cognition and developed a highly sensitive method to quantify native and oxidized cardiolipin species in human skeletal muscle. Preliminary data indicate that higher levels of tetralinoleoyl cardiolipin are associated with better physical and cognitive performance, whereas a greater proportion of oxidized cardiolipin predicts worse outcomes. Ongoing efforts aim to extend these findings to the brain using novel PET radioligands and advanced MRS techniques. Together, this work positions cardiolipin remodeling and mitochondrial quality control as central mechanisms of aging and promising targets for interventions to preserve physical and cognitive function in late life.

LRRK2 controls COX assembly through regulation of redox status of mitochondrial copper chaperones.

Baicalin triggers ferroptosis to suppress colorectal cancer via SLC25A28-UQCRC2-regulated electron transport chain disruption.

Immunometabolism: Is cyanide a missing link between metabolic pathways and immune function?

Metabolic adaptations in the hypothermic myocardium: Mechanisms and clinical implications.

Paternal BPA and BPS exposure induce testicular dysfunction in pubertal male offspring: roles of OCTN2 carnitine transporter disruption and exacerbated oxidative stress/apoptosis.

Developmental and metabolic toxicity of diphenyl phosphate: insights from an integrative mechanistic framework in zebrafish embryos.

Chromium-reducing Alcaligenes faecalis and chromium-tolerant Lysinibacillus macroides microbial communities for targeted remediation of chromium-contaminated soils and transcriptomic analysis.

In vivo chemogenetic generation of intraneuronal H2O2.

Carbon quantum dots as charge bridges: Photogenerated electrons flow alter microbial interactions and electron transfer networks in constructed wetlands.

A genomic view on lactic metabolism.

Comparative insights into denitrification performance and microbial adaptation of heterotrophic, autotrophic, and mixotrophic systems under florfenicol stress for recirculating mariculture wastewater treatment.

Synergistic improvement of methane production and phosphorus recovery from anaerobic digestion of waste activated sludge by Fe2O3-assisted electroactive microorganisms.

Revealing the mechanism of carboxyl groups on biochar filler for enhancing biodegradation of N,N-dimethylacetamide.

Molecular regulation of exercise training on hippocampal neuroprotection in post-traumatic brain injury: A systematic review.

Stage-specific FeS-mediated regulation of Paracoccus denitrificans during carbon consumption by machine learning-assisted comparative proteomics.

Magnetic properties driving nitrogen removal improvement in magnetite-enhanced activated sludge: Mechanistic insights and process validation.

Neuroprotective effect of berberine-loaded niosomes against brain injury in dyslipidemic rats: The interplay between oxidative stress, mitochondrial dysfunction and apoptotic signals.

Synergistic antibacterial effects and mechanisms of different phenolic acids against Shewanella putrefaciens from fish, with emphasis on the combination of gallic acid and caffeic acid.

Coated ferrous sulfate requirement for alleviating hypoxia-induced hepatopancreatic inflammation in sub-adult grass carp (Ctenopharyngodon idella).