Ageing through reproductive death in Caenorhabditis elegans

The nematode worm Caenorhabditis elegans has emerged as one of the premier model systems for ageing research. Its use has led to the discovery of many biological mechanisms of ageing conserved across species, including acceleration of ageing by insulin/IGF-1 signalling (IIS) and germline signalling. Ageing in C. elegans, however, is unusual in terms of the severity and early onset of senescent pathology, particularly affecting organs involved in reproduction. For example, in post-reproductive hermaphrodites, intestinal biomass is converted into yolk leading to intestinal atrophy and yolk steatosis. While late yolk production has long been viewed as futile, is it possible that it somehow promote fitness? Results in this thesis show that post-reproductive C. elegans hermaphrodites vent yolk that can be consumed by larvae, promoting their growth. Thus, post-reproductive mothers can contribute to reproductive fitness by converting their biomass into milk, suggesting that intestinal atrophy is a cost of lactation. This type of massive reproductive effort involving biomass repurposing leading to organ degeneration is characteristic of semelparous organisms (i.e. that exhibit only a single reproductive episode) ranging from monocarpic plants to Pacific salmon where it leads to rapid death (reproductive death). Results also show that lactation occurs in other hermaphroditic Caenorhabditis nematode species but not in females. Moreover, the latter do not exhibit intestinal atrophy or steatosis, and are longer lived suggesting that they do not undergo reproductive death. Furthermore, germline ablation strongly increases lifespan in hermaphrodites but not females; similarly, blocking sexual maturation e.g. by gonadectomy can greatly increase lifespan in other organisms that undergo reproductive death. IIS which accelerates C. elegans ageing is also shown to promote lactation. These results suggest that C. elegans hermaphrodites exhibit reproductive death, suppression of which increases lifespan. This has major implications in terms of what one can learn about human ageing from C. elegans

Biological Constraint as a Cause of Aging

Aging rate differs greatly between species, indicating that the process of senescence is largely genetically determined. Senescence evolves in part due to antagonistic pleiotropy (AP), where selection favors gene variants that increase fitness earlier in life but promote pathology later. Identifying the biological mechanisms by which AP causes senescence is key to understanding the endogenous causes of aging and its attendant diseases. Here we argue that the frequent occurrence of AP as a property of genes reflects the presence of constraint in the biological systems that they specify. This arises particularly because the functionally interconnected nature of biological systems constrains the simultaneous optimization of coupled traits (interconnection constraints), or because individual traits cannot evolve (impossibility constraints). We present an account of aging that integrates AP and biological constraint with recent programmatic aging concepts, including costly programs, quasi-programs, hyperfunction and hypofunction. We argue that AP mechanisms of costly programs and triggered quasi-programs are consequences of constraint, in which costs resulting from hyperfunction or hypofunction cause senescent pathology. Impossibility constraint can also cause hypofunction independently of AP. We also describe how AP corresponds to Stephen Jay Gould’s constraint-based concept of evolutionary spandrels, and argue that pathologies arising from AP are bad spandrels. Biological constraint is a missing link between ultimate and proximate causes of senescence, including diseases of aging. That this was not realized previously may reflect a combination of hyperadaptationism among evolutionary biologists, and the erroneous assumption by biogerontologists that molecular damage accumulation is the principal primary cause of aging

Semelparous Death as one Element of Iteroparous Aging Gone Large

The aging process in semelparous and iteroparous species is different, but how different? Death in semelparous organisms (e.g., Pacific salmon) results from suicidal reproductive effort (reproductive death). Aging (senescence) in iteroparous organisms such as humans is often viewed as a quite different process. Recent findings suggest that the nematode Caenorhabditis elegans, widely used to study aging, undergoes reproductive death. In post-reproductive C. elegans hermaphrodites, intestinal biomass is repurposed to produce yolk which when vented serves as a milk to support larval growth. This apparent benefit of lactation comes at the cost of intestinal atrophy in the mother. Germline removal and inhibition of insulin/IGF-1 signaling (IIS) suppress C. elegans reproductive pathology and greatly increase lifespan. Blocking sexual maturity, e.g., by gonadectomy, suppresses reproductive death thereby strongly increasing lifespan in semelparous organisms, but typically has little effect on lifespan in iteroparous ones. Similarly, reduced IIS causes relatively modest increases in lifespan in iteroparous organisms. We argue that the more regulated and plastic mechanisms of senescence in semelparous organisms, involving costly resource reallocation under endocrine control, exist as one extreme of an etiological continuum with mechanisms operative in iteroparous organisms. We suggest that reproductive death evolved by exaggeration of mechanisms operative in iteroparous species, where other mechanisms also promote senescence. Thus, knowledge of C. elegans senescence can guide understanding of mechanisms contributing to human aging

Is "cellular senescence" a misnomer?

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype, or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence, it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition, and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts, such cells are normal and healthy and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as "senescent." Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation-a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype)

Sem tí­tulo (EEPP) 2020

Resumo: Este artigo trata das inquietações suscitadas pela pandemia dentro de nosso ambiente acadêmico e das discussões e proposições para trabalhar com os obstáculos trazidos por essa. Especialmente aborda a experiência EEPP- Escultura Encontrada e Pintura Pronta, primeira temporada do instaurado Campo Remoto. O EEPP desenvolveu-se em cinco episódios, e abrangeu aspectos da Colagem, do Ready-Made e Object-trouvé, no perí­odo de 5 de agosto a 3 de setembro de 2020

Implementación de R Studio en el área Estadística en las carreras de Ingeniería

La inclusión de nuevas tecnologías en la formación de profesionales, especialmente en Ingeniería, propone desafíos constantes a los docentes de las áreas que necesitan herramientas de ese tipo para el tratamiento y resolución de problemas y prácticas, normalmente con gran cantidad de datos a tratar. Probabilidad y Estadísticas es una de estas áreas, que además se encuentra con la realidad de que los paquetes de tratamiento estadístico de datos requieren inversiones grandes y sostenidas, a la que no se acceden fácilmente. En la Facultad Regional San Nicolás (UTN), se solicitó una incorporación interdisciplinaria de las áreas de Informática y Probabilidad y Estadísticas, vinculadas a través del PID dirigido por la Dra. Ana Craveri, para investigar, elegir y poner en funcionamiento algún programa de tratamiento de datos que permitiera agilizar cálculos y motivar el proceso de enseñanza y aprendizaje en los alumnos de todas las ingenierías que se dictan en la facultad. Uno de los objetivos más notables, tiene que ver con el desarrollo de competencias de egreso de los futuros profesionales, en las que una herramienta de recopilación, tratamiento y emisión de información estadística, propone una solución actualizada, útil y de resultados notables.Ibero-American Science and Technology Education Consortiu

Implementación de R Studio en el área Estadística en las carreras de Ingeniería

La inclusión de nuevas tecnologías en la formación de profesionales, especialmente en Ingeniería, propone desafíos constantes a los docentes de las áreas que necesitan herramientas de ese tipo para el tratamiento y resolución de problemas y prácticas, normalmente con gran cantidad de datos a tratar. Probabilidad y Estadísticas es una de estas áreas, que además se encuentra con la realidad de que los paquetes de tratamiento estadístico de datos requieren inversiones grandes y sostenidas, a la que no se acceden fácilmente. En la Facultad Regional San Nicolás (UTN), se solicitó una incorporación interdisciplinaria de las áreas de Informática y Probabilidad y Estadísticas, vinculadas a través del PID dirigido por la Dra. Ana Craveri, para investigar, elegir y poner en funcionamiento algún programa de tratamiento de datos que permitiera agilizar cálculos y motivar el proceso de enseñanza y aprendizaje en los alumnos de todas las ingenierías que se dictan en la facultad. Uno de los objetivos más notables, tiene que ver con el desarrollo de competencias de egreso de los futuros profesionales, en las que una herramienta de recopilación, tratamiento y emisión de información estadística, propone una solución actualizada, útil y de resultados notables.Ibero-American Science and Technology Education Consortiu

Implementación de R Studio en el área Estadística en las carreras de Ingeniería

La inclusión de nuevas tecnologías en la formación de profesionales, especialmente en Ingeniería, propone desafíos constantes a los docentes de las áreas que necesitan herramientas de ese tipo para el tratamiento y resolución de problemas y prácticas, normalmente con gran cantidad de datos a tratar. Probabilidad y Estadísticas es una de estas áreas, que además se encuentra con la realidad de que los paquetes de tratamiento estadístico de datos requieren inversiones grandes y sostenidas, a la que no se acceden fácilmente. En la Facultad Regional San Nicolás (UTN), se solicitó una incorporación interdisciplinaria de las áreas de Informática y Probabilidad y Estadísticas, vinculadas a través del PID dirigido por la Dra. Ana Craveri, para investigar, elegir y poner en funcionamiento algún programa de tratamiento de datos que permitiera agilizar cálculos y motivar el proceso de enseñanza y aprendizaje en los alumnos de todas las ingenierías que se dictan en la facultad. Uno de los objetivos más notables, tiene que ver con el desarrollo de competencias de egreso de los futuros profesionales, en las que una herramienta de recopilación, tratamiento y emisión de información estadística, propone una solución actualizada, útil y de resultados notables.Ibero-American Science and Technology Education Consortiu