scholarly journals DAF-2/insulin IGF-1 receptor regulates mobility during ageing by integrating opposite inputs from muscle and neuronal tissues

2021 ◽  
Author(s):  
Charline Roy ◽  
Laurent Molin ◽  
Mathilde Solyga ◽  
Benjamin Bonneau ◽  
Camille Vachon ◽  
...  
Keyword(s):  
Early Adulthood ◽  
Good Health ◽  
Tissue Specific ◽  
C Elegans ◽  
Dependent Relationship ◽  
Age Related ◽  
Neuronal Tissues ◽  
Versatile Tool ◽  
Specific Degradation ◽  
Reduced Mobility

During ageing, preservation of locomotion is generally considered an indicator of sustained good health, in elderlies and in animal models. In C. elegans, mutants of the insulin receptor DAF-2 represent a paradigm of healthy ageing, as their increased lifespan is accompanied by a delay in age-related loss of mobility. However, these animals are less mobile than wild-type animals in early adulthood. Here we investigated the DAF-2-dependent relationship between longevity and mobility using an auxin-inducible degron to trigger tissue-specific degradation of endogenous DAF-2. As previously reported, inactivation of DAF-2 in neurons or intestine was sufficient to extend the lifespan of worms, whereas depletion in epidermis, germline or muscle was not. However, neither intestinal nor neuronal depletion of DAF-2 prevented the age-related loss of mobility. In 1-day-old adults, DAF-2 depletion in neurons reduced mobility, while muscle depletion had no effect. By contrast, DAF-2 depletion in the muscle of middle-age animals improved their mobility. The combination of neuronal and muscle effects thus mimics the global locomotor phenotype of daf-2 mutants. Yet, we observed that neuronal or muscle DAF-2 depletion both preserved the mitochondria network in ageing muscle. Overall, these results show that the mobility pattern of daf-2 mutants is determined by the sequential and opposing impact of neurons and muscle tissues and can be dissociated from the regulation of the lifespan. This work also provides the characterization of a versatile tool to analyze the tissue-specific contribution of insulin-like signaling in integrated phenotypes at the whole organism level.

scholarly journals Tissue-specific degradation of essential centrosome components reveals distinct microtubule populations at microtubule organizing centers

2018 ◽  
Author(s):  
Maria D. Sallee ◽  
Jennifer C. Zonka ◽  
Taylor D. Skokan ◽  
Brian C. Raftrey ◽  
Jessica L. Feldman
Keyword(s):  
Intestinal Epithelial ◽  
Microtubule Organization ◽  
Tissue Specific ◽  
Animal Development ◽  
Microtubule Organizing Centers ◽  
C Elegans ◽  
Differentiated Cells ◽  
Ring Complex ◽  
Specific Degradation ◽  
First Time

AbstractNon-centrosomal microtubule organizing centers (ncMTOCs) are found in most differentiated cells, but how these structures regulate microtubule organization and dynamics is largely unknown. We optimized a tissue-specific degradation system to test the role of the essential centrosomal microtubule nucleators γ-tubulin ring complex (γ-TURC) and AIR-1/Aurora A at the apical ncMTOC, where they both localize in C. elegans embryonic intestinal epithelial cells. As at the centrosome, the core γ-TURC component GIP-1/GCP3 is required to recruit other γ-TuRC components to the apical ncMTOC including MZT-1/MZT1, characterized here for the first time in animal development. In contrast, AIR-1 and MZT-1 were specifically required to recruit γ-TuRC to the centrosome, but not to centrioles or to the apical ncMTOC. Surprisingly, microtubules remain robustly organized at the apical ncMTOC upon γ-TuRC and AIR-1 co-depletion, and upon depletion of other known microtubule regulators including TPXL-1/TPX2, ZYG-9/chTOG, PTRN-1/CAMSAP, and NOCA-1/Ninein. However, loss of GIP-1 removed a subset of dynamic EBP-2/EB1-marked microtubules, and the remaining dynamic microtubules grew faster. Together, these results suggest that different MTOCs use discrete proteins for their function, and that the apical ncMTOC is composed of distinct populations of γ-TuRC-dependent and independent microtubules that compete for a limited pool of resources.

scholarly journals Centriole-less pericentriolar material serves as a microtubule organizing center at the base of C. elegans sensory cilia

2020 ◽  
Author(s):  
Jérémy Magescas ◽  
Sani Eskinazi ◽  
Michael V. Tran ◽  
Jessica L. Feldman
Keyword(s):  
Sensory Neurons ◽  
Super Resolution ◽  
Spatial Separation ◽  
Animal Cells ◽  
Microtubule Organizing Center ◽  
Tissue Specific ◽  
C Elegans ◽  
Organizing Center ◽  
Pericentriolar Material ◽  
Specific Degradation

SummaryDuring mitosis in animal cells, the centrosome acts as a microtubule organizing center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis while SPD-2/CEP192 and PCMD-1, which are essential in the zygote, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans [1-3], we find evidence for “centriole-less PCM” at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic microtubules towards the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved microtubule nucleator γ-TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.

How adolescents and adults translate motivational value to action: Age-related shifts in strategic physical effort exertion for monetary rewards

2019 ◽  
Author(s):  
Alexandra M Rodman ◽  
Katherine Powers ◽  
Catherine Insel ◽  
Erik K Kastman ◽  
Katherine Kabotyanski ◽  
...  
Keyword(s):  
Young Adults ◽  
Early Adulthood ◽  
Theoretical Models ◽  
Incentive Motivation ◽  
Reward Processing ◽  
Monetary Reward ◽  
Physical Effort ◽  
Monetary Rewards ◽  
Age Related ◽  
Adolescents And Adults

Adults titrate the degree of physical effort they are willing to expend according to the magnitude of reward they expect to obtain, a process guided by incentive motivation. However, it remains unclear whether adolescents, who are undergoing normative developmental changes in cognitive and reward processing, translate incentive motivation into action in a way that is similarly tuned to reward value and economical in effort utilization. The present study adapted a classic physical effort paradigm to quantify age-related changes in motivation-based and strategic markers of effort exertion for monetary rewards from adolescence to early adulthood. One hundred and three participants aged 12-23 years completed a task that involved exerting low or high amounts of physical effort, in the form of a hand grip, to earn low or high amounts of money. Adolescents and young adults exhibited highly similar incentive-modulated effort for reward according to measures of peak grip force and speed, suggesting that motivation for monetary reward is consistent across age. However, young adults expended energy more economically and strategically: whereas adolescents were prone to exert excess physical effort beyond what was required to earn reward, young adults were more likely to strategically prepare before each grip phase and conserve energy by opting out of low reward trials. This work extends theoretical models of development of incentive-driven behavior by demonstrating that layered on similarity in motivational value for monetary reward, there are important differences in the way behavior is flexibly adjusted in the presence of reward from adolescence to young adulthood.

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

scholarly journals Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mercedes M. Pérez-Jiménez ◽  
José M. Monje-Moreno ◽  
Ana María Brokate-Llanos ◽  
Mónica Venegas-Calerón ◽  
Alicia Sánchez-García ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Caenorhabditis Elegans ◽  
Protein Aggregation ◽  
Steroid Hormones ◽  
Sensory Neurons ◽  
Environmental Cues ◽  
Steroid Sulfatase ◽  
Loss Of Function ◽  
C Elegans ◽  
Age Related

AbstractAging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer’s disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.

Development of a model describing individuated adult child–parent relationships

2008 ◽  
Vol 32 (5) ◽  
pp. 381-389 ◽  
Author(s):  
Heike M. Buhl
Keyword(s):  
Early Adulthood ◽  
Adult Child ◽  
Measurement Model ◽  
Factor Analyses ◽  
Mothers And Fathers ◽  
Parent Relationships ◽  
Age Related ◽  
Mother Child Relationships ◽  
Over Time ◽  
Age Related Changes

This study investigates age-related changes and dyadic-specific differences in adult child–parent relationships. Using an individuation framework, two German samples of 224 and 105 participants aged between 21 and 47 years were administered the Network of Relationships Inventory, the Emotional Autonomy Scale and the Authority Reciprocity Questionnaire. Factor analyses resulted in a measurement model valid for adult children, their mothers and fathers. The model includes connectedness (with emotional and cognitive aspects) as well as individuality (assessed as power symmetry). Connectedness decreased with age. Symmetry in father–child relationships increased over time, while mother–child relationships were perceived to be symmetrical by early adulthood. Child–mother relationships were more connected than child–father relationships. Sons described themselves as more powerful than did daughters.

scholarly journals Autobiographical Memory in Normal Ageing and Dementia

1991 ◽  
Vol 4 (4) ◽  
pp. 235-248 ◽  
Author(s):  
Harvey J. Sagar ◽  
Edith V. Sullivan ◽  
Suzanne Corkin
Keyword(s):  
Memory Function ◽  
Early Adulthood ◽  
Normal Subjects ◽  
Elderly Subjects ◽  
Retrieval Cues ◽  
Age Related ◽  
Normal Ageing ◽  
Severity Of Dementia ◽  
And Control ◽  
Cue Words

Autobiographical memories in young and elderly normal subjects are drawn mostly from the recent past but elderly subjects relate a second peak of memories from early adulthood. Memory for remote past public events is relatively preserved in dementia, possibly reflecting integrity of semantic relative to episodic memory. We examined recall of specific, consistent autobiographical episodes in Alzheimer's disease (AD) in response to cue words. Patients and control subjects drew most memories from the recent 20 years: episode age related to anterograde memory function but not subject age or dementia. Subjects also related a secondary peak of memories from early adulthood; episode age related to subject age and severity of dementia. The results suggest that preferential recall of memories from early adulthood is based on the salience of retrieval cues, altered by age and dementia, superimposed on a temporal gradient of semantic memory. Further, AD shows behavioural similarity to normal ageing.

Transfer and tissue-specific accumulation of components in embryos of Caenorhabditis elegans and dolichura: in vivo analysis with a low-cost signal

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 317-330 ◽  
Author(s):  
O. Bossinger ◽  
E. Schierenberg
Keyword(s):  
Caenorhabditis Elegans ◽  
Low Cost ◽  
Free Living ◽  
Tissue Specific ◽  
C Elegans ◽  
Specific Accumulation ◽  
In Vivo Analysis

The pattern of autofluorescence in the two free-living namatodes Rhabditis dolichura and Caenorhabditis compared. In C. elegans, during later embryogenesis cells develop a typical bluish autofluorescence as illumination, while in Rh. dolichura a strong already present in the unfertilized egg. Using a new,

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