The telomere hypothesis of stress and aging

ABSTRACT: Telomeres are repetitive sequences of DNA forming the ends of chromosomes in eukaryotic organisms and are the focus of human aging studies. Cells accumulate wear and tear from day to day use, so they replicate, but their DNA can accumulate damage over time and be multiplied with each cell replication with harmful effects on the organism. Telomeres are thought to limit the lifespan of cells by ‘counting’ the number of cell replication events and triggering cell senescence or death when the maximum number of safe cell replications has been reached. Over time, these senescent cells accumulate and produce the physical signs of aging. However, tests of this hypothesis in non-model organisms do not support predictions suggesting the predominant theory of telomeres and aging is incomplete. In chapter 1, I propose an alternative hypothesis of telomere function and its relationship to stress and aging called, “The Telomere Hypothesis of Stress and Aging” (THSA) which incorporates an additional, previously underappreciated telomere function—their role in modulating expression of stress response genes. Genomic DNA is compacted into chromatin—a complex folding architecture which alters the activity of particular genes. Environmental stress triggers telomere shortening, cell metabolism slows, chromatin unfolds, and stress response genes are upregulated. Following chromatin remodeling some telomeres are re-lengthened and cell metabolism increases. Thus, the THSA predicts dynamic telomere length and cell metabolic rate that are related to levels of environmental stress exposure. In addition to formalizing the Telomere Hypothesis of Stress and Aging (THSA), If birds have higher levels of ALT than observed in mammals they should also have a greater capacity to re-lengthen telomeres in general. Thus, according to predictions of the THSA, on a gram for gram basis, birds are expected to lose telomeres more slowly with age than mammals. Whether or not this is true was previously unknown. I examine this question in Chapter 2; by comparing the rates of telomere loss with age between birds and mammal species. When comparing rates of telomere loss with age between birds and mammals, results were as predicted—for a given body size, birds lost telomeres with age at slower rates than mammals. Thus, results support the THSA—if birds possess higher rates of ALT this may account for their ability to achieve longer lifespans for the body size and metabolic rate. Longer-lived species of birds and mammals lost telomeres with age at slower rates than short lived ones. This is consistent with both the predominant paradigm and the THSA, except the THSA predicts a portion of telomere shortening with age is due to increasing up-regulation of stress response genes with age

CLASSIFICATION OF PALEOCHANNELS AND THEIR RELATIONSHIP TO SYNSEDIMENTARY FAULTING WITHIN THE LOWER ELKHON COAL ZONE, PIKEVILLE FORMATION, BREATHITT GROUP, SOUTHEASTERN KENTUCKY

Paleochannels are a major cause of roof failure in underground coal mines in southeastern Kentucky. Models that predict the location and geometry of paleochannels are essential to assist in mine planning and development. Data from approximately 506 coal exploration drill holes were subjected to second-order trend-surface analysis to identify stacking or offsetting relationships between sandstone bodies in adjacent stratigraphic intervals. The stacking of sandstone bodies within adjacent intervals suggests the presence of synsedimentary faulting. This model suggests that continued movement along the faults created topographic lows attracted paleodrainages and accommodated thick accumulations of sandstone in approximately the same areas through time. Trend-surface residuals analysis successfully located areas of potential synsedimentary faulting within the study area. An additional 7,189 elevation data points for the top of the Newman Limestone, interpreted from oil and gas records, were utilized to locate sub-Pennsylvanian System faults within the study area. The correlation between faults associated with the coal measures identified using second-order trend-surface analysis and faults affecting the Newman Limestone suggests Pennsylvanian synsedimentary faults were preceded by older Paleozoic fault movement. The greater availability of oil and gas subsurface data makes this relationship an important tool for predicting locations of fault-controlled coal measure paleochannels

Review of Come, Lord Jesus

This review examines John Piper\u27s 2023 Come, Lord Jesus. The book is shown to be a valuable contribution to the broader eschatological field, and a particular contribution to the Historic Premillennialist camp

Taking Dominion to End Dominion: The Mennonite Influence on the End of Russian Serfdom

Serfdom in Russia was abolished in 1861, only 76 years after the first Mennonites were invited into Russia by Catherine II. By examining the lifestyle of the Mennonites who settled in the agriculturally productive “New Russia” (modern-day Ukraine), as well as the impact that the Mennonites had on the Imperial family, peasantry, and government, it is evident that the Mennonites played a recognizable role in bringing about the abolition of serfdom across the empire

Subdivision Improvement Requirements and Guarantees: A Primer

This Article examines the subdivision improvement process in general and subdivision improvement requirements and guarantees in particular. Part II reviews the history of subdivision controls and the parties, interests, and themes involved in the subdivision control process. After this overview, Part III details the subdivision development process from the private and public sectors with particular emphasis on subdivision improvement requirements. Part IV surveys the case law regarding subdivision improvements. Finally, Part V evaluates the various methods for securing the completion of subdivision improvements and offers suggestions for reform

Batch to Single Piece Flow

Assess the current T1 Snap product line and propose a move from batch production to single piece flow

Urban Redevelopment and the Elimination of Blight: A Case Study of Missouri\u27s Chapter 353

The purpose of this Article is to consider carefully whether Chapter 353 was meant to be blight driven; that is, whether the Missouri legislature enacted Chapter 353 to remedy obvious cases of blight, or whether the legislature was equally concerned about promoting economic development within urban areas generally. Part I of the Article describes Chapter 353 and project approval under the statute. Part II examines the criticisms of the statute and several of the studies that have evaluated the effectiveness of Chapter 353. Next, Part III develops a legislative history for Chapter 353 in an effort to discern the objectives of the statute. Part IV of the Article evaluates the use of Chapter 353 in light of the public use doctrine, and Part V evaluates the use of the statute in light of legal challenges to blight determinations. Finally, Part VI of the Article develops conclusions about the proper role of blight determinations in urban renewal programs