-
[
Curr Biol,
2012]
Aging affects nearly all organisms, but how aging evolves is still unclear. The central prediction of classic theory is that high extrinsic mortality leads to accelerated aging and shorter intrinsic life span. However, this prediction considers mortality as a random process, whereas mortality in nature is likely to be condition dependent. Therefore, the novel theory maintains that condition dependence may dramatically alter, and even reverse, the classic pattern. We present experimental evidence for the evolution of longer life span under high condition-dependent mortality. We employed an experimental evolution design, using a nematode, Caenorhabditis remanei, that allowed us to disentangle the effects of mortality rate (high versus low) and mortality source (random versus condition dependent). We observed the evolution of shorter life span under high random mortality, confirming the classic prediction. In contrast, high condition-dependent mortality led to the evolution of longer life span, supporting a key role of condition dependence in the evolution of aging. This life-span extension was not the result of a trade-off with reproduction. By simultaneously corroborating the classic results [8-10] and providing the first experimental evidence for the novel theory, our study resolves apparent contradictions in the study of aging and challenges the traditional paradigm by demonstrating that condition-environment interactions dictate the evolutionary trajectory of aging.
-
[
Neuron,
2012]
The adult mammalian central nervous system exhibits restricted regenerative potential. Chen etal. (2011) and El Bejjani and Hammarlund (2012) used Caenorhabditis elegans to uncover intrinsic factors that inhibit regeneration of axotomized mature neurons, opening avenues for potential therapeutics.
-
[
Immunity,
2017]
IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen etal. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.
-
[
Nat Commun,
2024]
Myosin motors are critical for diverse motility functions, ranging from cytokinesis and endocytosis to muscle contraction. The UNC-45 chaperone controls myosin function mediating the folding, assembly, and degradation of the muscle protein. Here, we analyze the molecular mechanism of UNC-45 as a hub in myosin quality control. We show that UNC-45 forms discrete complexes with folded and unfolded myosin, forwarding them to downstream chaperones and E3 ligases. Structural analysis of a minimal chaperone:substrate complex reveals that UNC-45 binds to a conserved FX<sub>3</sub>HY motif in the myosin motor domain. Disrupting the observed interface by mutagenesis prevents myosin maturation leading to protein aggregation in vivo. We also show that a mutation in the FX<sub>3</sub>HY motif linked to the Freeman Sheldon Syndrome impairs UNC-45 assisted folding, reducing the level of functional myosin. These findings demonstrate that a faulty myosin quality control is a critical yet unexplored cause of human myopathies.
-
[
Dev Cell,
2016]
Temperature-sensing neurons in C.elegans reduce the life-shortening effects of high temperatures via steroid signaling. In this issue of Developmental Cell, Chen etal. (2016) elucidate the underlying mechanisms by which the transcription factor CREB induces the neuropeptide FLP-6 in the temperature-sensing neurons to counteract the life-shortening effects of high temperature.
-
[
Cell,
2014]
Surface receptors can link binding of ligands to changes in the actin-based cell cytoskeleton. Chia etal. and Chen etal. provide evidence for direct binding between the cytoplasmic tails ofreceptorsand the WAVE complex, a regulator of the actin nucleator Arp2/3 complex, which mighthelp to explain how environmental signals are translated into changes in morphology andmotility.
-
[
Lab Chip,
2013]
Caenorhabditis (C.) elegans is a model animal used in genetics, neuroscience, and developmental biology. Researchers often immobilize squirming worms to obtain high-quality images for analysis. However, current methods usually require physical contact or anesthetics. This can cause injuries to worm bodies or neuron disturbances. This study presents an alternative technique, called addressable light-induced heat knockdown (ALINK), to effectively immobilize worms by using light-induced sublethal heat. A microchip composed of an indium-tin-oxide (ITO) glass plate and an ITO glass plate coated with a photoconductive layer (a-Si:H) was produced. Worms to be immobilized were immersed in a liquid medium and sandwiched between the two plates. When the worms were irradiated with a focused laser beam in the presence of electric fields (referred to as an optoelectric treatment), the optoelectric effect heated the liquid medium. The neural functions of the worms shut down temporarily when a critical temperature (>31 C) was reached. Their neural functions resumed after the heat source was removed. A temperature above 37 C killed all worms. Using short-wavelength light reduced the worms' recovery time. An equivalent circuit was modeled to predict the operating modes, and an optoelectric treatment with a high-concentration medium enhanced rapid heating. A safe operating range (20 Vpp (peak-to-peak voltage), 100 kHz to 10 MHz, 31 to 37 C) to induce heat knockdown (KD) was also investigated. The results show that the heat KD was well controlled, autonomous, and reversible. This technique can be used for worm immobilization.
-
[
Mol Neurodegener,
2015]
The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan
-
[
Bio Protoc,
2016]
The rate of oxygen consumption is a vital marker indicating cellular function during lifetime under normal or metabolically challenged conditions. It is used broadly to study mitochondrial function (Artal-Sanz and Tavernarakis, 2009; Palikaras et al., 2015; Ryu et al., 2016) or investigate factors mediating the switch from oxidative phosphorylation to aerobic glycolysis (Chen et al., 2015; Vander Heiden et al., 2009). In this protocol, we describe a method for the determination of oxygen consumption rates in the nematode Caenorhabditis elegans.
-
[
STAR Protoc,
2021]
Live-cell imaging analysis provides tremendous information for the study of cellular events such as growth cone migration in neuronal development. Here, we describe a protocol for live-cell imaging of migrating PVD dendritic growth cones in the nematode <i>C.elegans</i> by spinning-disk confocal microscopy. Fluorescently labeled growth cones and cytoskeletal proteins could be continuously observed for 4-6h in mid-stage larvae. This protocol is suitable for revealing the dynamic molecular and cellular events in dendrite and axon development of <i>C.elegans</i>. For complete details on the use and execution of this protocol, please refer to Chen etal. (2019).