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Lab in the news 

© Johannes Tkadletz

New metabolic pathway uncovered linked with impaired glucose uptake in aging

Our research has linked the GPCPD1-GPC metabolic pathway, involving Glycerophosphocholine Phosphodiesterase 1 (GPCPD1) and its substrate glycerophosphocholine (GPC), to impaired muscle glucose uptake. Genetic inactivation led to severe glucose intolerance in mice, highlighting potential pathologies.

Aging is a primary risk factor for GPCPD1-GPC dysfunction, with our research revealing a strong correlation with advanced chronological age and dysfunctionality of the pathway in humans. Additionally, the pathway dysfunction occurs in type 2 diabetes patients, underscoring its importance in human glucose homeostasis.

Read more in:

Gpcpd1-GPC metabolic pathway is dysfunctional in aging and its deficiency severely perturbs glucose metabolism.

Cikes D et al Nature Aging (2024)

Shimona Starling (2024) Metabolism. Dysfunctional lipid metabolism in ageing muscle: effects on glucose tolerance. Nature Reviews Endocrinology

Art by Fly Azure
 Elsayad Lab, CACB, Med Uni Wien

Innovative non-invasive imaging method developed for real-time measurement of biomechanics at the picosecond and micrometer levels

Biological processes are shaped by both chemical factors and physical forces, occurring at both macro and microscopic scales. Existing measurement methods often involve invasive techniques, potentially impacting the studied biology over time.

In an exciting interdisciplinary study with the Elsayad Lab at Meduni Vienna, a novel contact-free method has been developed operating to study directional (anisotropic) mechanical changes in cells at micrometer and picosecond scales. This innovative technology revealed the diverse nature of transitions between elastic and viscous states of subcellular components and how these give rise to and are essential for anisotropic growth and intracellular organization. The technique opens the door to further exploration of their functional significance in diverse processes relevant for life and how these may be perturbed in different pathologies.

Read more in:

Brillouin light scattering anisotropy microscopy for imaging the viscoelastic anisotropy in living cells

Hamid Keshmiri*, Domagoj Cikes* et al. Nature Photonics  (Equal contribution) (2024)

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© CikesLab

PCYT2 enzyme linked to
muscle aging and healthspan

Sarcopenia, characterized by the loss of muscle mass and strength, stands as a prominent feature of aging, impacting the healthspan of millions globally.

We have identified  Phosphate Ethanolamine Cytidylyltransferase 2 (PCYT2) as pivotal in this process. By examining a rare inherited human disorder displaying aging-like traits, we have unveiled the identical molecular mechanism underlying this aging phenomenon. Leveraging advanced imaging technologies, we have illuminated a previously unrecognized biological pathway contributing to this debilitating condition. Finally, employing a gene therapy-based approach, we successfully alleviated symptoms of the disease in both mutant and aged animals, highlighting PCYT2 as a novel molecular participant and a promising therapeutic target in the realm of muscle aging biology.

Read more in:

PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing.

Cikes D, et al Nature Metabolism (2023)

- Highlited in Bianca Nogrady (2023) Enzyme loss linked to age related muscle wasting. Nature Middle East

- Featured in Science News (2023) Muscle health depends on lipid synthesis. ScienceDaily

- Featured in Research Briefing (2023) A conserved role for PCYT2-regulated lipid biosynthesis in muscle health and ageing. Nature Metabolism

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