Mechanistic aspects of mitochondrial-stress control of longevity

The aging process is concurrently modulated by genetic factors, dietary habits and environmental exposures. Mitochondria are key modulators of the aging process and represent central hubs in response to different types of genetic, environmental and dietary interventions. Through state-of-the-art approaches our lab exploits the nematode Caenorhabditis elegans, as a powerful genetically tractable model organism for aging studies.

In this project we systematically characterize in vivo phenotypic and behavioral consequence elicited by mitochondrial-targeting interventions during aging and in models of age-associated neurodegenerative disorders (e.g. Alzheimer, Parkinson). Moreover, targeted approaches looking at cell death and survival signaling pathways (e.g. autophagy, iron-regulated mechanisms, neuronal specific genes) as well as unbiased strategies such as -omics analyses and compounds and genetic screenings, are concurrently used to unravel molecular mechanisms underlying mitochondrial-stress control of aging and associated neurodegenerative processes, with the ultimate goal of extending healthy lifespan.

Long-standing collaborations with Profs Nektarios Tavernarakis, Bart Braeckman, Björn Schumacher, Francesco Cecconi and Hilde Nilsen nicely contribute to this project.

  1. Schiavi A, Torgovnick A, Kell A, Megalou E, Castelein N, Guccini I, Marzocchella L, Gelino S, Hansen M, Malisan F, Condo I, Bei R, Rea SL, Braeckman BP, Tavernarakis N, Testi R, Ventura N. (2013) Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. Exp Gerontol 48: 191-201
  2. Arczewska KD, Tomazella GG, Lindvall JM, Kassahun H, Maglioni S, Torgovnick A, Henriksson J, Matilainen O, Marquis BJ, Nelson BC, Jaruga P, Babaie E, Holmberg CI, Burglin TR, Ventura N, Thiede B, Nilsen H. (2013) Active transcriptomic and proteomic reprogramming in the C. elegans nucleotide excision repair mutant xpa-1. Nucleic Acids Res 41: 5368-5381
  3. Torgovnick A, Schiavi A, Maglioni S, Ventura N. (2013) Healthy aging: what can we learn from Caenorhabditis elegans? Z Gerontol Geriatr 46: 623-628. Review
  4. Maglioni S, Schiavi A, Runci A, Shaik A, Ventura N. (2014) Mitochondrial stress extends lifespan in C. elegans through neuronal hormesis. Exp Gerontol 56:89-98
  5. Tigges J, Krutmann J, Fritsche E, Haendeler J, Schaal H, Fischer JW, Kalfalah F, Reinke H, Reifenberger G, Stühler K, Ventura N, Gundermann S, Boukamp B, Boege F. (2014) The Hallmarks of Fibroblast Ageing. Mech Age Dev 44:138-26. Review
  6. Schiavi A, Ventura N. (2014) The interplay between mitochondria and autophagy and its role in the aging process. Exp Gerontol 56:147-53. Review
  7. Schiavi A, Maglioni S, Palikaras K, Shaik A, Strapazzon F, Brinkmann V, Torgovnick A, Castelein N, De Henau S, Braeckman BP, Cecconi F, Tavernarakis N, Ventura N. (2015) Iron-Starvation-Induced Mitophagy Mediates Lifespan Extension upon Mitochondrial Stress in C. elegans. Curr Biol. 25(14):1810-22
  8. Shaik A, Schiavi A, Ventura N. (2016) Mitochondrial autophagy promotes healthy aging. Cell Cycle. Jul 17;15(14):1805-6. Commentary
  9. Schiavi A and Ventura N. (2016) Mitochondrial longevity pathways. Springer International Publishing Switzerland. Ageing: Lessons from C. elegans, Healthy Ageing and Longevity 5, DOI 10.1007/978-3-319-44703-2_5. Book chapter
  10. Torgovnick A*, Schiavi A*, Shaik A^, Kassahun H^, Maglioni S, Rea SL, Johnson TE, Reinhardt HC, Honnen S, Schumacher B, Nilsen H, Ventura N. (2018) BRCA1/BARD1 mediate apoptosis resistance but not longevity in response to mitochondrial stress in C. elegans. EMBO Reports. Oct 26. Dec;19(12). pii: e45856
  11. Schiavi A, Strappazzon F, Ventura N. (2020). Iron metabolism regulated mitophagy in aging and associated neuronal pathologies. Mech Age Dev. Review

Funded by:

  • AIRC (MFAG11509)
  • Forschungskommission, Medical Faculty, HHU (34/2013)
  • DFG (VE663/3-1)
  • Forschungskommission, Medical Faculty, HHU (38/2016)


Natascia Ventura, MD, PhD, PD
Alfonso Schiavi, PhD
Margherita Romeo, PhD

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