Reduction of Lipid Accumulation Reverses Aging

Background:

Age is a key risk factor for cardiovascular disease such as atherosclerosis, which is characterized by endothelial dysfunction, extracellular matrix remodeling, lipid accumulation, chronic inflammation and increased ferroptosis. However, there is currently no effective therapeutic that directly targets the cellular and metabolic drivers of vascular aging. Most interventions delay progression but do not reverse the aging phenotype at the molecular level. This technology offers a therapeutic strategy to treat age-related cardiovascular disease and restore cardiovascular function.

Technology Overview:

This University at Buffalo technology uncovers a previously unrecognized regulator of vascular aging.  Loss of molecular expression in aged vascular cells is associated with impaired lipid oxidation, excessive lipid accumulation and increased ferroptosis. Knockdown models in young endothelial cells (EC) and vascular smooth muscle cells (VSMC) induced hallmark features of aging, including DNA damage, impaired proliferation, and ferroptotic stress. These mice show symptoms of premature aging, including progressive weight loss, abnormal posture and marked curvature of the spine and significantly shorter life-span (103 days as compared to more than 2 years for the wild-type mice). They also exhibit significant cardiovascular problems and accelerated skeletal muscle aging. Therapeutic treatment successfully restored lipid homeostasis, suppressed ferroptosis and reversed age-related hallmarks, such as expression of senescence-associated beta-galactosidase, decreased DNA damage, decreased inflammation, and improved overall function in both in vitro and in vivo models. Furthermore, studies observed significantly improved extracellular matrix (ECM) integrity and arterial endothelial function.  This technology provides a therapeutic agent for age-related cardiovascular disease through restoration of vascular lipid homeostasis.

Advantages:

• Increased myofiber size
• Increased body weight
• Increased ambulatory time and distance
• Enhanced muscle regeneration after injury
• Expanded ability of muscle to generate force (twitch and tetanic forces)
• Improved activity of arterial eNOS, the enzyme responsible for nitric oxide production and vasodilation for improved blood flow
• Improved ECM composition, e.g., collagen and elastin, within aged arteries
• Increased lipid oxidation in mitochondria
• Decreased lipid accumulation in aged arteries and muscle
• Increased autophagy

Applications:

• Therapeutic use
• Clinical progress monitoring
• Research tool

Intellectual Property Summary:

US Provisional Patent Application 63/812,744 filed on May 27, 2025

Stage of Development:

Completion of in vitro and in vivo studies in mouse models.

Licensing Status:

Available for licensing or collaboration.