Review in Aging Cell Identifies Mitochondrial Dynamics as Shared Target for Cardio-Cerebral Comorbidity

A systematic review in Aging Cell identifies mitochondrial fission and fusion dynamics as a shared therapeutic target for age-related cardiac and neurodegenerative diseases, highlighting potential intervention pathways like SGLT2 inhibitors and NAD+ precursors.

Researchers from Shengjing Hospital of China Medical University published a systematic review in Aging Cell analyzing the dysregulation of mitochondrial dynamics in age-related cardiovascular and neurodegenerative diseases.

The authors summarized how imbalances in mitochondrial fission and fusion—specifically driven by the hyperactivation of pro-fission dynamin-related protein 1 (Drp1) and the degradation of pro-fusion proteins Mfn1, Mfn2, and Opa1—drive pathophysiology across Alzheimer's disease, Parkinson's disease, cerebral infarction, and heart failure.

The review highlighted various pharmacological and physiological interventions that have shown potential in alleviating these imbalances in preclinical models, including SGLT2 inhibitors (dapagliflozin and empagliflozin), metformin, captopril, melatonin, nicotinamide riboside, and physical exercise.

With global population aging driving a rise in multi-organ degenerative diseases, identifying common molecular hubs like mitochondrial dynamics is critical for developing multi-target therapeutics.

The review stresses that therapeutic progress depends on 'bidirectional regulation'—rebalancing the fusion-fission ratio and maintaining mitochondrial-ER contact site (MAM) integrity—rather than simply applying broad-spectrum fission inhibitors, which often cause systemic toxicity.

The work underscores the translational gaps in the field, noting that while numerous natural products and peptides show preclinical efficacy in rodents, validation in humanized co-comorbidity models and clinical cohorts is currently lacking.

The comprehensive cataloging of mitochondrial dynamics pathways supports the therapeutic hypotheses of companies developing mitophagy-inducing small molecules and mitochondrial transplantation technologies.

Preclinical confirmation that SGLT2 inhibitors and NAD+ precursors (like nicotinamide riboside) regulate mitochondrial dynamics provides additional scientific rationale for their clinical evaluation in metabolic and neurodegenerative longevity trials.

The review highlights a commercial shift in drug discovery toward conformation-selective Drp1 modulators and targeted mitochondrial delivery vectors (such as MITO Porter and lipid conjugates) to improve bio-availability and reduce off-target toxicity.

The development and clinical validation of sensitive biomarkers, such as circulating mitochondrial-derived vesicles, to monitor real-time mitochondrial function in aging patients.

The design of future clinical trials assessing the synergistic effects of selective mitochondrial dynamics modulators alongside established cardiovascular and reperfusion therapies.