Detail

Keywords

Aging; Caenorhabditis elegans; Cell Biology; Fibroblasts; Genes, rRNA; Keratinocytes; Mice; Microscopy; Protein Synthesis Inhibitors; Regulatory Sequences, Ribonucleic Acid; Ribosomes; Skin Aging; Spectrum Analysis, Raman

Research group(s)

• Christian Doppler Laboratory for Skin Multimodal Imaging of Aging and Senescence - SKINMAGINE
  Head: Florian Gruber
  Research Area: We investigate how environmental stress, pollution and time lead to accumulation of senescent cells in the skin and how these contribute to skin aging. Our focus lies on the SASP, the metabolism and the quality control of aging cells.
  Members:
  Florian Gruber
  Markus Schosserer
• Schosserer Lab
  Members:
  Markus Schosserer

Research interests

One of the significant challenges modern medicine and biology face today is the continuously increasing life expectancy of the population and, consequently, the increase in age-related pathologies. Since the changes in physiology and morphology of organisms, tissues, and cells during their life span are still poorly understood, it is vital to gain insight into the molecular mechanisms of aging and aging-associated pathologies to design strategies that maximize the human health span. Therefore, our research focuses on understanding the cellular and molecular changes that occur during aging, how these changes affect tissue functionality, and where and how repair and regeneration must counteract these changes.

More specifically, we are studying modifications of RNA, collectively called the "epitranscriptome", and their impact on general and specific protein synthesis. Our lab recently discovered that the RNA methyltransferase NSUN5 is one of the few highly conserved genes modulating longevity. We revealed that protein synthesis in cells could be "reprogrammed" by reducing NSUN5 levels and extending the lifespans of flies, worms, and baker's yeast. Thus, we aim to identify other RNA-modifying enzymes that can also modulate aging and stress resistance in nematodes, mice, and various human cellular aging models.

Techniques, methods & infrastructure

The human skin is the most exposed organ to factors that accelerate aging. One factor, cellular senescence, has recently been identified as crucial in the functional decline during aging. It is well established that up to 20% of skin cells are senescent at an advanced age. However, the influence of senescent cells on the microenvironment in the human skin is not fully understood. Senescent cells acquire a senescence-associated secretory phenotype (SASP) which leads to the secretion of soluble signaling factors and thus changes the micro-environment drastically. Together with colleagues at the Department of Dermatology, the Technical University of Vienna, and CHANEL Parfums Beauté in the CD-Laboratory "SKINMAGINE", we characterize the effect of plant extracts on cellular senescence of skin cells and how this might relate to skin functionality in aging. Therefore, we apply advanced microscopy techniques, such as Raman microspectroscopy, and multimodal integration of different imaging techniques.

Grants

• Targeting the epitranscriptome to promote healthy lifespan (2023)
  Source of Funding: National Institutes of Health (NIH), Hevolution/AFAR New Investigator Award in Biology and Geroscience Research
  Principal Investigator
• Targeting cellular senescence based on inter-organelle communication, multi-level proteostasis and metabolic control (SENIOPROM) (2022)
  Source of Funding: FWF (Austrian Science Fund), Research Group
  Principal Investigator
• Targeting the epitranscriptome to promote healthy lifespan (2022)
  Source of Funding: National Institutes of Health (NIH), Hevolution/AFAR New Investigator Award in Biology and Geroscience Research
  Principal Investigator
• CD-Lab for Multimodal Imaging of Aging and Senescence of the Skin (SKINMAGINE) (2020)
  Source of Funding: CDG (Christian Doppler Research Association), Christian Doppler Laboratory
  Principal Investigator

Selected publications

1. Yang, G. et al. (2024) ‘2′-O-ribose methylation levels of ribosomal RNA distinguish different types of growth arrest in human dermal fibroblasts’, Journal of Cell Science, 137(3). Available at: https://doi.org/10.1242/jcs.261930.
2. Wagner, A. and Schosserer, M. (2022) ‘The epitranscriptome in ageing and stress resistance: A systematic review’, Ageing Research Reviews, 81, p. 101700. Available at: https://doi.org/10.1016/j.arr.2022.101700.
3. Heissenberger, C. et al. (2020) ‘The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans’, eLife, 9. Available at: https://doi.org/10.7554/elife.56205.
4. Heissenberger, C. et al. (2019) ‘Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth’, Nucleic Acids Research, 47(22), pp. 11807–11825. Available at: https://doi.org/10.1093/nar/gkz1043.
5. Schosserer, M. et al. (2015) ‘Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan’, Nature Communications, 6(1). Available at: https://doi.org/10.1038/ncomms7158.