Aging is a phenomenon that brings about the onset of many diseases and increases mortality. Understanding aging mechanisms can help us increase longevity and delay the onset of multiple chronic diseases. It has been previously observed that dietary restriction is a method that increases lifespan and delays the loss of function caused by age-associated pathologies. We used the roundworm, Caenhorbabditis elegans, to dissect the mechanisms of dietary restriction-induced longevity. Specifically, we focused on the phenomenon of adult reproductive diapause (ARD). ARD is induced when pre-reproductive juvenile larvae are subjected to starvation. Upon reintroduction to food after prolonged starvation, ARD worms undergo a morphological rejuvenation and resume a normal lifespan. Mechanisms that control post-diapause recovery are still quite unknown. We have found that the TGF-β/BMP signaling pathway is required for post ARD rejuvenation. The TGF-beta signaling pathway is a critical factor for growth processes including cell growth, differentiation, embryonic development, and much more. We aimed to characterize the role of this signaling pathway in ARD maintenance and post-ARD recovery. We hypothesized that TGF-β/BMP mutants accumulate excessive amounts of cellular damage during ARD and are unable to recover from ARD. To address this hypothesis, we analyzed markers of cellular aging among diapaused animals using fluorescent microscopy, in both wild type and TGF-β/BMP mutants. Using transgenic fluorescent reporter strains we examined pH, nucleolar morphology, mitochondria, and cytoskeleton and nucleoskeleton integrity for aging-associated phenotypes. These insights can help us understand the role of the conserved TGF-β/BMP pathway in dietary restriction induced longevity.

Aging is associated with a decline in functionality and cellular organization. These changes are reflected in the morphology of cellular organelles, such as the cytoskeleton, which plays an integral role in cell movement and signaling. Age-related changes in the cytoskeletal system make it a great point of interest in age-related studies. However, its roles in aging and longevity are still largely unknown. We hypothesized that alteration of the actin cytoskeleton results in an accumulation of age-related cellular pathologies. To test this hypothesis, we examined cellular markers of aging in C. elegans worms with deactivated actin proteins. The genes for the cytoskeletal system are well conserved between humans and Caenorhabditis elegans, making it a great and popular model system for examining the role of the cytoskeleton in aging. We used RNA interference (RNAi) to knock down the expression of cytoskeletal actins in the worms. Afterwards, we used fluorescent microscopy to examine markers of cellular aging: pH, nucleoskeleton integrity morphology, and mitochondrial network morphology. We have found that perturbation of actin cytoskeleton partially mimics age-related cellular changes. We expect the results to be of help in the ongoing study of the role of the cellular cytoskeletal complex in the human aging process.

Aging is characterized by the increasing loss of physiological and cellular functionality, however the mechanism that underlies this deterioration is still unclear. Emerging evidence indicates that aging is associated with increased cell-to-cell variation in gene expression within tissues: homologous cells within tissues express the same gene at varying levels. The causes of this age-related variation of gene expression are not known. Here we aim to investigate the mechanisms of increased cell-to-cell variation in gene expression with age using C. elegans as a model system. By characterizing aging in C. elegans, we hope to provide further insight into the molecular characteristics of aging in humans, and possible points of intervention. We hypothesize that stochastic noise of transcription can lead to increased gene expression variation with age. Previously we have found that stochastic noise of gene expression is incredibly restricted in young C. elegans animals. Using quantitative fluorescent microscopy we have analyzed expression of reporter genes in old animals and have dissected the potential contribution of stochastic transcription noise into age-related variation of gene expression.