The Aging Process and Cancerogenesis

Failla, G.

doi:10.1111/j.1749-6632.1958.tb54674.x

Cited by 36 publications

(21 citation statements)

References 5 publications

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“…Accumulation of somatic mutations, due to imperfect repair and maintenance, has since long been implicated as a universal, major cause of aging [2], [3], but proved difficult to study in higher organisms. Most somatic DNA mutation assays are indirect and based on alterations in phenotypic characteristics, such as the mouse or Drosophila spot tests [4], [5].…”

Section: Introductionmentioning

confidence: 99%

Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster

et al. 2010

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Using a transgenic mouse model harboring a mutation reporter gene that can be efficiently recovered from genomic DNA, we previously demonstrated that mutations accumulate in aging mice in a tissue-specific manner. Applying a recently developed, similar reporter-based assay in Drosophila melanogaster, we now show that the mutation frequency at the lacZ locus in somatic tissue of flies is about three times as high as in mouse tissues, with a much higher fraction of large genome rearrangements. Similar to mice, somatic mutations in the fly also accumulate as a function of age, but they do so much more quickly at higher temperature, a condition which in invertebrates is associated with decreased life span. Most mutations were found to accumulate in the thorax and less in abdomen, suggesting the highly oxidative flight muscles as a possible source of genotoxic stress. These results show that somatic mutation loads in short-lived flies are much more severe than in the much longer-lived mice, with the mutation rate in flies proportional to biological rather than chronological aging.

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Section: Introductionmentioning

confidence: 99%

Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster

et al. 2010

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“…Genomic instability, defined simply as unintended alterations occurring in the genome 26, has been hypothesized to be central to aging for over half a century, as exemplified by the proposal of the Somatic Mutation Theory of Aging 2728. This has been supported by evidence that the integrity of DNA is constantly challenged by chemical, physical, and biological agents that react with DNA 29, and that somatic mutations accumulate in cells of aging humans and model organisms 30.…”

Section: Genomic Instabilitymentioning

confidence: 99%

Evidence for the hallmarks of human aging in replicatively aging yeast

Janssens

Veenhoff

2016

Microbial Cell

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Recently, efforts have been made to characterize the hallmarks that accompany and contribute to the phenomenon of aging, as most relevant for humans 1. Remarkably, studying the finite lifespan of the single cell eukaryote budding yeast (recently reviewed in 2 and 3) has been paramount for our understanding of aging. Here, we compile observations from literature over the past decades of research on replicatively aging yeast to highlight how the hallmarks of aging in humans are present in yeast. We find strong evidence for the majority of these, and summarize how yeast aging is especially characterized by the hallmarks of genomic instability, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, and mitochondrial dysfunction.

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“…Interestingly, Harman is one of the only modern scientists to explicitly declare that “aging may also be viewed as a disease” (Harman, 1991, p. 5362). Another prominent voice for the importance of stochastic processes is Hayflick (1994) who identifies entropy and the loss of molecular fidelity that arises from it as a fundamental cause of senescence (see also Failla, 1958; Orgel, 1963; Finch and Kirkwood, 2000). …”

Section: Stochastic Effectsmentioning

confidence: 99%

Does senescence give rise to disease?

Carnes

Staats

Sonntag

2008

Mechanisms of Ageing and Development

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The distinctions between senescence and disease are blurred in the literature of evolutionary biology, biodemography, biogerontology and medicine. Theories of senescence that have emerged over the past several decades are based on the concepts that organisms are a byproduct of imperfect structural designs built with imperfect materials and maintained by imperfect processes. Senescence is a complex mixture of processes rather than a monolithic process. Senescence and disease have overlapping biological consequences. Senescence gives rise to disease, but disease does not give rise to senescence. Current data indicate that treatment of disease can delay the age of death but there are no convincing data that these interventions alter senescence. An understanding of these basic tenets suggests that there are biological limits to duration of life and the life expectancy of populations and reveal biological domains where the development of interventions and/or treatments may modulate senescence.

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The Aging Process and Cancerogenesis

Cited by 36 publications

References 5 publications

Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster

Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster

Evidence for the hallmarks of human aging in replicatively aging yeast

Does senescence give rise to disease?

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