Cardiovascular Disease Mortality
Cardiovascular disease (CVD) is a major contributor to global mortality, with its incidence and prevalence increasing with age. Age-related deterioration of cardiovascular homeostasis is linked to cellular senescence, oxidative stress, insulin signaling dysregulation, autophagy impairment, and chronic inflammation.
Rejuvenation Strategies
Cellular rejuvenation approaches aim to counteract age-related CVD effects. Strategies include:
- Cellular Reprogramming: Restoring youthful function to aged cardiac cells through in vitro, in vivo, or partial reprogramming.
- Inflammation Management: Inhibiting inflammatory processes to alleviate CVD.
- Senolytics Therapy: Clearing senescent cells to improve myocardial function and reduce atherosclerosis.
- Metabolic Manipulation: Targeting mitochondrial function and metabolic pathways to improve cellular health.
- Epigenetic Rejuvenation: Resetting epigenetic clocks to restore youthful gene expression.
- Immune Rejuvenation: Enhancing immune function to better manage inflammation.
- Circadian Clock Restoration: Optimizing circadian rhythms to reduce inflammation and improve metabolic homeostasis.
- Lifestyle Interventions: Dietary restriction and exercise to improve metabolism, reduce inflammation, and enhance DNA repair.
Biomarkers and CVD Mortality
Prognostic biomarkers like elevated blood pressure, diabetes, LDL cholesterol, and CRP indicate increased risk for cardiovascular events and mortality. Susceptibility/risk biomarkers such as CRP and LDL cholesterol identify individuals at risk of developing CVD. Validated surrogate endpoints like LDL cholesterol reduction and blood pressure reduction are directly related to preventing CVD mortality.
Physical Activity and CVD Mortality
Regular physical activity significantly reduces CVD mortality risk. Studies show that exceeding recommended exercise levels—300 to 599 minutes weekly of moderate activity or 150 to 299 minutes of vigorous activity—lowers CVD mortality by 28% to 38% and 27% to 33%, respectively. Combining moderate and vigorous activity can reduce mortality risk by 35% to 42%.
Reprogramming-Induced Rejuvenation (RIR)
RIR aims to reverse cellular and organismal aging, holding potential for CVD outcomes. By rejuvenating cells, RIR could improve cardiovascular health through enhanced cellular function, tissue regeneration, reduced inflammation, and improved proteostasis. However, safety concerns like teratoma formation and oncogene activation require further research.
Conclusion
Addressing CVD mortality involves a multifaceted approach, including lifestyle interventions, cellular rejuvenation strategies, and biomarker-based risk assessment. While promising, these methods require further validation to safely translate into clinical practice.