Age-dependent changes of nuclear morphology are uncoupled from longevity in Caenorhabditis elegans IGF/insulin receptor daf-2 mutants

Abstract

Nuclear envelope (NE) architecture and aging have been associated since the discovery that certain human progeria diseases are due to perturbations in processing of lamin A protein, generating alterations in NE morphology. However, whether changes in the NE are a causal effect of normal and premature aging is still controversial. Caenorhabditis elegans is a model organism where observations supporting both, dependent and independent roles of nuclear architecture in the aging process, have been reported.Using this model organism, we found that the long-lived glp-1 mutant and dietary restriction delayed age-associated nuclear morphology changes. In addition, we observed that the long-lived mutant of the insulin/IGF receptor daf-2 delayed the agedependent changes of nuclear architecture at 25ºC, as previously described. However, when daf-2 animals were incubated at 20ºC they remained long-lived, but nuclear appearance changed at similar rate as in the wild type. This supports the idea that both phenotypes, longevity and maintenance of nuclear architecture are tightly associated but can be separated and argues that nuclear morphology deterioration is not a cause of the natural aging process.

Cell Biology of theCaenorhabditis elegansNucleus

“…This suggests that altered nuclear morphology and longevity can be uncoupled, and that changes in nuclear shape are not the main driver of aging. A similar conclusion was reached by Pérez-Jiménez et al (2014), who found that in daf-2 mutant worms grown at 20°, which have increased longevity, irregular nuclear morphology occurred at the same age as in wild-type worms.…”

“…Moreover, the repressive H3K27me3 modification is lost as cells age (Jin et al 2011). As discussed above, the nucleus of aging worms undergoes morphological changes reminiscent of aging cells in mammals, although the two phenomena can be genetically uncoupled (Pérez-Jiménez et al 2014). The link in C. elegans between nuclear morphology in aging cells and gene expression is not known: does altered nuclear morphology affect the ability of chromatin to associate with the nuclear periphery, and if so, does that lead to changes in gene expression that affect the aging process?…”

Caenorhabditis elegans as a Useful Model for Studying Aging Mutations

“…Post-translational modifications of DAF-16 include its phosphorylation by AMPK ( 70 ). AMPK modulation of lifespan has been shown to occur also via CREB-regulated transcriptional coactivators in response to low levels of energy ( 35 ) ( Figure 1 ).…”

Prohibitin in Adipose and Immune Functions

“…The exact cellular and molecular mediators responsible for integrating these two extreme metabolic states of obesity and caloric restriction to immune function are beginning to be revealed. A perturbation of the IGF/insulin signaling cascade is known to increase longevity in C. elegans, which appears to be mediated though metabolic effects at the systemic level [80]. Of note, PHB promotes longevity in C. elegans, depending on metabolic status and genetic background [37], and PHB modulates insulin signaling in a phosphorylation-dependent manner [8,81].…”