scholarly journals Fractional re-distribution among cell motility states during ageing

2020 ◽  
Author(s):  
Jude M. Phillip ◽  
Nahuel Zamponi ◽  
Madonna P. Phillip ◽  
Jena Daya ◽  
Shaun McGovern ◽  
...  

ABSTRACTAgeing in humans is associated with a decreased capacity to regulate cell physiology. Cellular properties, such as cell morphology and cell mechanics, encode ageing information and as a result can be used as robust ageing biomarkers. Using a panel of dermal fibroblasts derived from healthy donors spanning a wide age range, we observe an age-related reduction in average cell motility, which we show is not due to the decreased motility of all cells, but results from fractional re-distribution among motility states. By taking advantage of the single-cell nature of our motility data, we show that cells can be classified based on spatial and activity patterns that define age-dependent motility states. These findings highlight an important feature of ageing cells shown by the decrease in the heterogeneity of cell movement in older adults, that potentially offer new mechanistic insights into the ageing process and avenues for novel biomarker development.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jude M. Phillip ◽  
Nahuel Zamponi ◽  
Madonna P. Phillip ◽  
Jena Daya ◽  
Shaun McGovern ◽  
...  

AbstractAgeing in humans is associated with the decreased capacity to regulate cell physiology. Cellular properties, such as cell morphology and mechanics, encode ageing information, and can therefore be used as robust biomarkers of ageing. Using a panel of dermal fibroblasts derived from healthy donors spanning a wide age range, we observe an age-associated decrease in cell motility. By taking advantage of the single-cell nature of our motility data, we classified cells based on spatial and activity patterns to define age-dependent motility states. We show that the age-dependent decrease in cell motility is not due to the reduced motility of all cells, but results from the fractional re-distribution among motility states. These findings highlight an important feature of ageing cells characterized by a reduction of cellular heterogeneity in older adults relative to post-adolescent/adults. Furthermore, these results point to a mechanistic framework of ageing, with potential applications in deciphering emergent ageing phenotypes and biomarker development.


PEDIATRICS ◽  
1978 ◽  
Vol 62 (5) ◽  
pp. 706-712 ◽  
Author(s):  
Jeane S. McCarthy ◽  
Leonor G. Zies ◽  
Henry Gelband

Indomethacin has been shown to be effective in closing a patent ductus arteriosus (PDA) in small premature infants. However, the age range over which this therapy is effective remains undetermined. Eighteen infants ranging in age from 4 to 45 days were studied. All had auscultatory and clinical findings indicative of PDA. Seventeen had roentgenographic evidence of cardiomegly and/or increased pulmonary vascular markings, and eight had ECG evidence of ventricular hypertrophy. Indomethacin was administered to most patients in two doses of 0.1 to 0.3 mg/kg 24 hours apart. In eight of 12 patients, 3 week of age or younger, the PDA closed after indomethacin therapy. Two patients had a decrease in the intensity of murmur and improvement of congestive heart failure after treatment, but the PDA did not close completely. Only patients 33 weeks of age (actual age) or younger responded to indomethacin therapy with complete ductal closure. The condition of patients 34 to 36 weeks of age improved but there was not complete closure; in patients older than 36 weeks there was no response. The data suggest an age-related mechanism for PDA closure and that treatment with indomethacin before 33 weeks of age is probably required. A role for prostaglandin in ductal patency is postulated.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254858
Author(s):  
Eman Ahmed El-Attar ◽  
Tamer A. Hosny ◽  
Kiyoshi Ichihara ◽  
Rania N. Bedair ◽  
Ahmed Salah El-Din Tork

Background Anti-Müllerian hormone (AMH) is an important determinant of ovarian reserve in fertility workups in many clinical settings. Thus, we investigated the age dependent decline in AMH specific to the Egyptian population and sought to establish an age dependent reference interval parametrically. Methods Serum samples were collected from 841 apparently healthy women. AMH was measured using an electro-chemiluminescent technique. Box-Cox power transformation was used to make the AMH distribution Gaussian for parametric derivation of reference intervals. Results Power of 0.4 was found optimal for Gaussian transformation of AMH reference values. We demonstrate the strong negative relation between circulating AMH and female age with Spearman’s correlation coefficient of rS = −0.528. Age-specific reference interval was determined for every 5 years of age from 16 to 49, and nomogram was constructed by smoothing the lines connecting adjacent lower and upper reference limits. Conclusion The age-specific reference intervals and the age-AMH nomogram could be valuable in the clinical practice of in reproductive medicine. To our knowledge, this is the first study to confirm AMH levels in Egyptian females. We were able to explore age-related AMH levels specific to Egyptian females in the fertile age group and to treat skewed AMH data in a multi-step scheme using power transformation. Thus, a more accurate nomogram was constructed accommodating a profile delineated for a wide age range and a rescaled AMH axis improving its usability.


2021 ◽  
Author(s):  
Damien Rei ◽  
Soham Saha ◽  
Marianne Haddad ◽  
Anna Haider Rubio ◽  
Marie-Noelle Ungeheuer ◽  
...  

AbstractAging is known to be associated with hippocampus-dependent memory decline, but the underlying causes of this age-related memory impairment are not yet elucidated. Here we show that the colonization of mice with the gut microbiota from aged, but not young animals is sufficient to trigger profound hippocampal alterations including astrogliosis, decreased adult neurogenesis, decreased novelty-induced neuronal activation and impairment in hippocampal-dependent memory. Similar alterations were reported in mice following the transfer of microbiota from aged human healthy donors. To decipher the mechanisms involved in mediating these microbiota-induced effects on brain functioning, we mapped the neuronal activity patterns and report that aged-microbiota transplantation reduced neuronal activity upstream to the vagus nerve. Targeted pharmacogenetic manipulation of the ascending branch of the vagus nerve demonstrated that the mere decrease in vagal activity was also detrimental to hippocampal functions. In contrast, increasing vagal activity alleviated the adverse effects of age-associated microbiota transfer on hippocampal functions and reinstated normal hippocampal memory in aged mice. We conclude that vagus nerve stimulation is a potential therapeutic strategy to lessen microbiota-dependent age-associated impairments in hippocampal functions.Graphical abstract


Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093422 ◽  
Author(s):  
Michael N. Moore

Autophagy has been strongly linked with hormesis, however, it is only relatively recently that the mechanistic basis underlying this association has begun to emerge. Lysosomal autophagy is a group of processes that degrade proteins, protein aggregates, membranes, organelles, segregated regions of cytoplasm, and even parts of the nucleus in eukaryotic cells. These degradative processes are evolutionarily very ancient and provide a survival capability for cells that are stressed or injured. Autophagy and autophagic dysfunction have been linked with many aspects of cell physiology and pathology in disease processes; and there is now intense interest in identifying various therapeutic strategies involving its regulation. The main regulatory pathway for augmented autophagy is the mechanistic target of rapamycin (mTOR) cell signaling, although other pathways can be involved, such as 5′-adenosine monophosphate-activated protein kinase. Mechanistic target of rapamycin is a key player in the many highly interconnected intracellular signaling pathways and is responsible for the control of cell growth among other processes. Inhibition of mTOR (specifically dephosphorylation of mTOR complex 1) triggers augmented autophagy and the search is on the find inhibitors that can induce hormetic responses that may be suitable for treating many diseases, including many cancers, type 2 diabetes, and age-related neurodegenerative conditions.


Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 801
Author(s):  
Jehun Choi ◽  
Gwi-Yeong Jang ◽  
Jeonghoon Lee ◽  
Hae-Young Chung ◽  
Hyung-Jun Noh ◽  
...  

Senescence is the phenomenon by which physiological functions of organisms degenerate with time. Cellular senescence is marked by an inhibition of cell cycle progression. Beta-galactosidase accumulates in the lysosomes of aged cells. In this study, human dermal fibroblast cells (HDFs) were treated with 0.5 μM doxorubicin for 4 h to induce cellular senescence. Senescence-associated beta-galactosidase (SA-β-gal) activity was then measured 72 h after treatment with aerial parts of Dendranthema zawadskii var. lucidum (Nakai) J.H. Park (DZ) extract. Treatment with DZ extract significantly decreased SA-β-gal activity in a dose-dependent manner in HDFs. Additionally, DZ extract treatment reduced age-related oxidative stress and inflammation in the aortas of aged rats. The reactive oxygen species (ROS) levels in aortas of aged control rats were higher than those in young rats. However, DZ extract-fed aged rats showed significantly lower ROS levels than the aged control rats. When the aged rats were treated with DZ extract at either 0.2 or 1.0 mg∙kg−1∙day−1, NF-κB levels in aorta tissue decreased significantly compared to those in aorta tissue of the aged control rats without DZ treatment. In addition, DZ extract-fed aged rat aortas showed significant reductions in expression of iNOS and COX-2 induced by NF-κB translocation. Therefore, these results suggest that DZ effectively inhibited senescence-related NF-κB activation and inflammation. DZ extract may have a role in the prevention of the vascular inflammatory responses that occur during vascular aging.


2002 ◽  
Vol 13 (01) ◽  
pp. 001-013 ◽  
Author(s):  
James Jerger ◽  
Rebecca Estes

We studied auditory evoked responses to the apparent movement of a burst of noise in the horizontal plane. Event-related potentials (ERPs) were measured in three groups of participants: children in the age range from 9 to 12 years, young adults in the age range from 18 to 34 years, and seniors in the age range from 65 to 80 years. The topographic distribution of grand-averaged ERP activity was substantially greater over the right hemisphere in children and seniors but slightly greater over the left hemisphere in young adults. This finding may be related to age-related differences in the extent to which judgments of sound movement are based on displacement versus velocity information.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bert Thys ◽  
Andrea S. Grunst ◽  
Nicky Staes ◽  
Rianne Pinxten ◽  
Marcel Eens ◽  
...  

AbstractQuantifying variation in behaviour-related genes provides insight into the evolutionary potential of repeatable among-individual variation in behaviour (i.e. personality). Yet, individuals typically also plastically adjust their behaviour in response to environmental conditions and/or age, thereby complicating the detection of genotype–phenotype associations. Here, using a population of free-living great tits (Parus major), we assessed the association between single nucleotide polymorphisms (SNPs) in the serotonin transporter gene (SERT) and two repeatable behavioural traits, i.e. female-female aggression and female hissing behaviour. For female-female aggression, a trait showing age-related plasticity, we found no evidence for associations with SERT SNPs, even when assessing potential age-dependent effects of SERT genotype on aggression. We also found no strong support for associations between SERT SNPs and hissing behaviour, yet we identified two synonymous polymorphisms (exon 13 SNP66 and exon 12 SNP144) of particular interest, each explaining about 1.3% of the total variation in hissing behaviour. Overall, our results contribute to the general understanding of the biological underpinning of complex behavioural traits and will facilitate further (meta-analytic) research on behaviour-related genes. Moreover, we emphasize that future molecular genetic studies should consider age-dependent genotype–phenotype associations for behavioural trait (co)variation, as this will vastly improve our understanding of the proximate causes and ultimate consequences of personality variation in natural populations.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 616-617
Author(s):  
Corinna Tanner ◽  
Michael Caserta ◽  
Jia-Wen Guo ◽  
Margaret Clayton ◽  
Paul Bernstein ◽  
...  

Abstract This mixed method study describes posttraumatic growth (PTG) accruing form experience with vision loss caused by severe age related macular degeneration (AMD) and explores relationships between depression, social support, and cognitive processing, on the path to PTG. Research describing the psychological and social issues surrounding AMD has focused on negative outcomes. However, learning from highly challenging experiences, such as vision loss, can offer benefits. In this study, these included an increased sense of personal strength, increased spirituality, and empathy for others (all domains of PTG). 89 participants with severe vision loss (mean age = 85.3 years, age range = 74–98 years) completed the interviewer-administered composite questionnaire, which identified elements of Tedeschi and Calhoun’s model of PTG. Relationships between variables were examined using path analysis. Findings were contextualized with data from 15 qualitative interviews. Findings underscored the importance of supportive others and deliberate cognitive processing in the path to PTG.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
James Moore ◽  
Rashid Akbergenov ◽  
Martina Nigri ◽  
Patricia Isnard-Petit ◽  
Amandine Grimm ◽  
...  

AbstractRandom errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy. Resulting transgenic mice were mosaic and showed a muscle-related phenotype with reduced grip strength. Analysis of gene expression in skeletal muscle using RNA-Seq revealed transcriptomic changes occurring in an age-dependent manner, involving an interplay of PGC1α, FOXO3, mTOR, and glucocorticoids as key signaling pathways, and finally resulting in activation of a muscle atrophy program. Our results highlight the relevance of translation accuracy, and show how disturbances thereof may contribute to age-related pathologies.


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