Apoptosis, or programmed cell death, is a mechanism in embryonic development that occurs naturally in organisms. Apoptosis is a different process from cell necrosis, which is uncontrolled cell death usually after infection or specific trauma. As cells rapidly proliferate during development, some of them undergo apoptosis, which is necessary for many stages in development, including neural development, reduction in egg cells (oocytes) at birth, as well as the shaping of fingers and vestigial organs in humans and other animals. Sydney Brenner, H. Robert Horvitz, and John E. Sulston received the Nobel Prize in Physiology or Medicine in 2002 for their work on the genetic regulation of organ development and programmed cell death. Research on cell lineages before and after embryonic development may lead to new ways to reduce or promote cell death, which can be important in preventing diseases such as Alzheimer's or cancer.
In 2003, molecular biology and genetics researchers Coleen T. Murphy, Steven A. McCarroll, Cornelia I. Bargmann, Andrew Fraser, Ravi S. Kamath, Julie Ahringer, Hao Li, and Cynthia Kenyon conducted an experiment that investigated the cellular aging in, Caenorhabditis elegans (C. elegans) nematodes. The researchers investigated the interactions between the transcription factor DAF-16 and the genes that regulate the production of an insulin-like growth factor 1 (IGF-1-like) protein related to the development, reproduction, and aging in C. elegans. Transcription factors, like DAF-16, are proteins that regulate the transcription of deoxyribonucleic acid (DNA) into messenger ribonucleic acid (mRNA), which later determines which proteins the cell produces. The research team's experiment suggested that an increase in the activity of the DAF-16 protein decreases the transcription of the genes that regulate the production of IGF-1-like proteins, increasing lifespan in nematodes. The team published their results in the article 'Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans' in Nature in June 2003. By comparing the regulation of gene expression in C. elegans with similar genes and pathways in humans, Murphy's research team sought to better understand cellular function and aging in humans.
Victor Ambros is a professor of molecular medicine at the University of Massachusetts Medical School, and he discovered the first microRNA (miRNA) in 1993. Ambros researched the genetic control of developmental timing in the nematode worm Caenorhabditis elegans and he helped describe gene function and regulation during the worm’s development and embryogenesis. His discovery of miRNA marked the beginning of research into a form of genetic regulation found throughout diverse life forms from plants to humans. Ambros is a central figure in the miRNA and C. elegans research communities, and co-directs the RNA Therapeutics Institute.
Once perceived as an unimportant occurrence in living organisms, cell degeneration was reconfigured as an important biological phenomenon in development, aging, health, and diseases in the twentieth century. This dissertation tells a twentieth-century history of scientific investigations on cell degeneration, including cell death and aging. By describing four central developments in cell degeneration research with the four major chapters, I trace the emergence of the degenerating cell as a scientific object, describe the generations of a variety of concepts, interpretations and usages associated with cell death and aging, and analyze the transforming influences of the rising cell degeneration research.