Early Adult Death Research Articles

Shorter life and reduced fecundity can increase colony fitness in virtual Caenorhabditis elegans.

In the nematode Caenorhabditis elegans, loss of function of many genes leads to increases in lifespan, sometimes of a very large magnitude. Could this reflect the occurrence of programmed death that, like apoptosis of cells, promotes fitness? The notion that programmed death evolves as a mechanism to remove worn out, old individuals in order to increase food availability for kin is not supported by classic evolutionary theory for most species. However, it may apply in organisms with colonies of closely related individuals such as C. elegans in which largely clonal populations subsist on spatially limited food patches. Here, we ask whether food competition between nonreproductive adults and their clonal progeny could favor programmed death by using an in silico model of C. elegans. Colony fitness was estimated as yield of dauer larva propagules from a limited food patch. Simulations showed that not only shorter lifespan but also shorter reproductive span and reduced adult feeding rate can increase colony fitness, potentially by reducing futile food consumption. Early adult death was particularly beneficial when adult food consumption rate was high. These results imply that programmed, adaptive death could promote colony fitness in C. elegans through a consumer sacrifice mechanism. Thus, C. elegans lifespan may be limited not by aging in the usual sense but rather by apoptosis‐like programmed death.

Peripheral Expression of Mutant Huntingtin is a Critical Determinant of Weight Loss and Metabolic Disturbances in Huntington\u2019s Disease

Deteriorating weight loss in patients with Huntington’s disease (HD) is a complicated peripheral manifestation and the cause remains poorly understood. Studies suggest that body weight strongly influences the clinical progression rate of HD and thereby offers a valuable target for therapeutic interventions. Mutant huntingtin (mHTT) is ubiquitously expressed and could induce toxicity by directly acting in the peripheral tissues. We investigated the effects of selective expression of mHTT exon1 in fat body (FB; functionally equivalent to human adipose tissue and liver) using transgenic Drosophila. We find that FB-autonomous expression of mHTT exon1 is intrinsically toxic and causes chronic weight loss in the flies despite progressive hyperphagia, and early adult death. Moreover, flies exhibit loss of intracellular lipid stores, and decline in the systemic levels of lipids and carbohydrates which aggravates over time, representing metabolic defects. At the cellular level, besides impairment, cell death also occurs with the formation of mHTT aggregates in the FB. These findings indicate that FB-autonomous expression of mHTT alone is sufficient to cause metabolic abnormalities and emaciation in vivo without any neurodegenerative cues.

Parental Loss and Residential Instability: The Impact on Young Women from Low-Income Households in Detroit

High poverty urban areas in the U.S. are over-burdened by early adult death and disability, yet there has been little documentation of how early parental death impacts youth residing in these communities. We conducted qualitative, community-based research on the health and well-being of 20 residentially unstable young women ages 18–24 in Detroit during 2011–2012. Participants were selected through their association with a local social service organization. We found that nine of these 20 young women had experienced the loss of a parent or primary caretaker during childhood or adolescence. Using data from in-depth, semi-structured interviews, this paper explores the role of parental loss as a precipitating event for residential instability and episodic homelessness. For these young women, parental loss was a catalyst for subsequent periods of intermittent homelessness and persistent mobility between the households of extended family and friends. These narratives provide unique testimony to the impact of early parental loss on young women from low-income households in an economically-stressed urban context in the U.S. Their stories highlight the dynamic associations between periods of housing insecurity and vulnerability to numerous social risks, including sexual commerce, acute stress, and alienation from social support networks. In this context, parental loss reflects a broader social inequality of early adult mortality in high poverty areas, and the health and social gains to be realized through targeted policies to support areas of urban economic crisis.

The Role of Genealogy and Clinical Family Histories in Documenting Possible Inheritance Patterns for Diabetes Mellitus in the Pre-Insulin Era

Part 2 presents detailed genealogic information on Josephine Imperato's paternal and maternal lineages extending from four to seven generations into the nineteenth and eighteenth centuries. Among these lineages are some where early adult death over successive generations is perhaps indicative of type 2 diabetes mellitus (type 2 DM). These lineages, all in the town of San Prisco in Italy, include both paternal and maternal ones with the following surnames: Casaccia, Casertano, Cipriano, de Angelis, de Paulis, Peccerillo, Foniciello, di Monaco, Vaccarella, Valenziano, Ventriglia, and Zibella. Genealogic studies of eighteenth and nineteenth century vital records in this area of Italy cannot definitively establish type 2 diabetes mellitus as either an immediate or contributory cause of death. This is because causes of death were not recorded and because disease diagnostic capabilities were largely absent. Genealogic studies of those who lived in Italy in the eighteenth and nineteenth centuries can at best provide data on approximate age at time of death. Early adult death in this era was not uncommon. However, its presence over several successive generations in a lineage raises the possibility of inherited diseases prominent among which is type 2 DM.

Season of birth is not associated with risk of early adult death in rural Senegal.

In a rural area of the Gambia, West Africa, young adults born in the 'hungry' season had a high excess of deaths (mortality ratios (MR): 3.7 from 14.5 years and 10.3 from 25 years, P < 0.0001). Among several potential causal factors, fetal undernutrition was considered the most plausible. This study is a similar analysis of children and young adults living in rural Senegal, close to the Gambia. A cohort of 9192 subjects born 1962-2001 with prospectively collected dates of birth and death was analysed. MR by season of birth (July-December/January-June) was estimated using Cox's proportional hazards analysis. The nutritional status of non-pregnant women was analysed at monthly intervals 1990-1996. MR by season of birth was slightly greater than 1 during infancy, and close to 1 from 1-5 years and from 5-14.5 years. From 14.5 years old the MR was 0.77 (95% CI: 0.47, 1.25, P = 0.29), compared with 0.53 (95% CI: 0.28, 1.02, P = 0.056) from 20 years and 0.33 (95% CI: 0.09, 1.25, P = 0.10) from 25 years. The weight of women varied strongly by season: means were 3.0-3.9 kg lower at the end of the rainy season (September-November) than during the dry season (February-May, P < 0.001 for each year). This study found no increased risk of death among young adults born during the hungry season in a rural West African area despite large seasonal variations in women's nutritional status. The strongly increased risk in adult Gambians is probably not explained by fetal undernutrition.

Expanded polyglutamine peptides alone are intrinsically cytotoxic and cause neurodegeneration in Drosophila

Several dominant, late-onset neurodegenerative diseases (e.g. Huntington's disease) are caused by expansion of polyglutamine (polyQ) repeats within specific proteins. The diverse, yet overlapping, pathology of these diseases could be due to novel deleterious functions unique to each protein or to a common pathophysiology mediated by the long polyQ chains themselves. By engineering Drosophila to express different polyQ peptides, we find that expanded polyQ chains alone are intrinsically cytotoxic and cause neuronal degeneration and early adult death. We further find that this intrinsic toxicity is dependent on cell type and polyQ length and that the inclusion of other amino acids modifies and reduces toxicity. This is the first in vivo evidence that polyQs, when removed from their disease gene context, cause neurotoxicity. These studies provide a basis for understanding the diverse clinical presentations in terms of the intrinsic cytotoxic effect of polyQ peptides being modulated by protein context. Parallel experiments in which cytotoxic polyQ expansions were engineered into Dishevelled, a Drosophila protein containing a naturally occurring polyQ tract, strongly suggest that the effect of a toxic polyQ peptide can be neutralized by protein context. This animal model provides a simple and effective means of screening for therapeutics that relieves the polyQ-induced lethality, independent of any particular disease gene. By quantifying the degree of lethality in several transgenic lines, we have identified a number of genetically modified strains that are suitable for eventual testing of compounds or genes that ameliorate the pathology of polyQ peptides.

Dietary habits and the prediction of life span of rats: a prospective test

A multivariable statistical model for predicting the duration of life of rats permitted to select their own diets was evaluated prospectively. With information relating to pre-adult dietary habits and growth responses, the predicted length of life for an individual closely matched the observed life span; the average absolute error was 11%. This suggests that, even under normal feeding conditions, the diet/growth history is an important factor bearing on death rate. In general, an early adult death age is associated with a high food intake prior to adulthood particularly when coupled with a high efficiency of food utilization during the post-puberty period, a rapid growth rate and early attainment of mature weight. Deviations from this pattern serve to increase the duration of life of the individual.