Ageing research in model organisms has accomplished great strides in finding genes and pathways that modulate the ageing process. However, the mechanism through which organisms age still remains a mystery. An influential ageing theory views ageing as the result of damage accumulation throughout an organism’s lifespan, which eventually accumulates to noxious levels causing death. In this thesis we will explore an alternative theory proposed by M. Blagosklonny. The hyperfunction theory postulates that ageing is the result of the non-adaptive continuation of developmental and reproductive programmes in late adulthood. Thus, programmes that promote growth and reproductive fitness become quasi-programmes in later life that result in age-related pathologies, some of which cause death. In this thesis we examined two reproductive pathologies, yolk accumulation and gonad degeneration, to try to understand their causes and to test their role in age-related mortality. A clear example of a quasi-programme in ageing worms is the run-on of yolk production in post-reproductive worms. During reproduction yolk is synthesized in the intestine to be transported to oocytes and provision embryogenesis. After reproduction ceases yolk protein accumulates in the body cavity of the worm. We found that yolk proteins accumulate to high levels during ageing. However, RNAi abrogation of vitellogenesis did not increase lifespan, implying that yolk protein accumulation does not cause mortality. Gonad disintegration provides an intriguing example of how quasi-programmes can cause pathology via atrophy. We found that gonad disintegration, which occurs in post-reproductive hermaphrodite worms, is apoptosis dependant. At least half of all germ cells undergo “physiological” programmed cell death. Our results imply that the apoptotic program that ensures reproductive fitness to support oocyte growth continues in older worms giving rise to pathology.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626681 |
| Date | January 2014 |
| Creators | De La Guardia, Y. I. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1430458/ |
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