By contrast in the old days, it was a big investment to study a hypothesis, and only the best candidates had a shot. Wacholder suggests researchers revise their statistical methods to account for " prior probability ," which is a subjective but reasonable measure of how plausible the gene-disease association in question looked before the study ref. Others suggests bigger sample sizes and more family-based studies.
These avoid a confounder called population stratification , the tendency of populations to carry high frequencies of both certain genes and certain diseases owing to mere accidents of ancestry : studies with family-based controls and larger sample sizes are more likely to be replicated ref. Researchers should treat any finding cautiously until it's replicated, preferably more than once. No effort to address the problem is completewithout a renewed call to publish more negative findings showing no gene-disease association. Such findings often go unpublished, bolstering false impressions of spurious gene-disease associations.
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Citations Publications citing this paper. Chemotherapy in conjoint aging-tumor systems: some simple models for addressing coupled aging-cancer dynamics Mitra Shojania Feizabadi , Tarynn M. Third, current field studies provide data on mortality and reproductive senescence but give limited opportunity for assays on other functional declines, or at least sources of mortality e. A very limited subset of organisms has been used to study aging in both the laboratory and the wild. Guppies are theoretically amenable to combining a laboratory approach with field estimates of mortality, aging patterns and functional declines in a single comparative study.
The guppy model, however, illustrates many of the challenges to be overcome. They inhabit temporary savanna pools and have evolved naturally short lifespans as a response to annual desiccation of their habitats.watch
Intrinsic mutagenesis, a genetic approach to ageing ( edition) | Open Library
Their synchronous hatching ensures that all individuals in a population are challenged by the same environmental conditions. A study of their aging in the wild, however, has not been accomplished. Other taxa, despite their longer lifespan, may also be suitable to combine field and laboratory aging assays e. To my knowledge, there has been just one study, using a single population of a neriid fly, which has combined estimates of aging in the wild and under laboratory conditions on the same natural population.
While this pioneering study was illuminating, several drawbacks may have masked important insights. Furthermore, only actuarial aging was studied, with functional responses at the physiological, histological, gene expression and reproductive level untested. Further challenges for studies on matched wild and captive populations include maternal and epigenetic effects that have the potential to affect laboratory assays.
Maternal effects arising from differential allocation of maternal provisioning among offspring, or from the environment experienced by the mother early in life, can potentially introduce a confounding component into common garden conditions, creating false variation ascribed to genetic background; though this could be mitigated by experimental design e.
As an extension, epigenetic effects can potentially affect life histories for multiple generations Dias and Ressler and can be even more difficult to control. Research on epigenetic effects is a burgeoning research field and new insights will increase our understanding of their impact on longevity and aging rates at both the population and individual levels.
Two studies have directly compared outbred captive primate populations with wild, unmanaged populations of the same species. This highlights the importance of carefully choosing the measure of functional decline as wild populations, despite experiencing clear aging, have much shorter lives.
Further insights can be gleaned from specific contrasts between natural and laboratory conditions. A key goal is to integrate data from wild and laboratory assays by encompassing demographic approaches actuarial aging with organismal deterioration at the behavioral, physiological, cellular and reproductive levels. I believe that substantial insights into aging will be obtained by comparing aging rates in matched populations exposed to natural and laboratory conditions, using individuals from replicated populations within species exposed to contrasting selection regimes such as different risks of mortality.
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Abstract Aging is an increase in mortality risk with age due to a decline in vital functions. Introduction Aging senescence is an increase in mortality risk with age due to deterioration of vital functions. Figure 1 Open in figure viewer PowerPoint.
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Figure 2 Open in figure viewer PowerPoint. Partitioning variation in mortality. Schematic illustration of how different components of aging can modify adult lifespan, with special reference to the effect of intrinsic and extrinsic mortality. Populations can differ in the rate of aging i.
Intrinsic mutagenesis, a genetic approach to ageing
Figure 3 Open in figure viewer PowerPoint. Question Hypothesis Approach Challenges Solutions How does demographic actuarial aging vary across populations within a species? Is interpopulation variation in lifespan lower in captivity than in the wild? Challenges in Combining Field and Laboratory Assays The main challenge to combining research in the wild and the laboratory using matching populations is that animals amenable to lifetime observation in the wild are generally not amenable to rearing in captivity and vice versa due to their size, lifespan or environmental requirements.
Current Insights from Interpopulation Comparisons Two studies have directly compared outbred captive primate populations with wild, unmanaged populations of the same species. Conflict of Interest None declared. Abrams, P.
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