scholarly journals Loxl2 is a mediator of cardiac aging in Drosophila melanogaster; genetically examining the role of aging clock genes

2021 ◽  
Author(s):  
Mark J Bouska ◽  
Hua Bai
Keyword(s):  
Drosophila Melanogaster ◽  
Clock Genes ◽  
Turning Points ◽  
Whole Body ◽  
Specific Gene ◽  
Age Related ◽  
Human Orthologs ◽  
Age Range ◽  
Transcriptional Target

Abstract Transcriptomic, proteomic, and methylation aging clocks demonstrate that aging has a predictable preset program, while Transcriptome Trajectory Turning Points indicate that the 20 to 40 age range in humans is the likely stage at which the progressive loss of homeostatic control, and in turn aging, begins to have detrimental effects. Turning points in this age range overlapping with human aging clock genes revealed five candidates that we hypothesized could play a role in aging or age-related physiological decline. To examine these gene’s effects on lifespan and health-span, we utilized whole body and heart specific gene knockdown of human orthologs in Drosophila melanogaster. Whole body Loxl2, fz3, and Glo1 RNAi positively affected lifespan as did heart-specific Loxl2 knockdown. Loxl2 inhibition concurrently reduced age-related cardiac arrythmia and collagen (Pericardin) fiber width. Loxl2 binds several transcription factors in humans and RT-qPCR confirmed that a conserved transcriptional target CDH1 (Drosophila CadN2), has expression levels which correlate with Loxl2 reduction in Drosophila. These results point to conserved pathways and multiple mechanisms by which inhibition of Loxl2 can be beneficial to heart health and organismal aging.

Ageism, Personal and Others’ Perceptions of Age Awareness, and Their Interactive Effect on Subjective Accelerated Aging

2020 ◽  
pp. 073346482096720
Author(s):  
Yoav S. Bergman ◽  
Yuval Palgi
Keyword(s):  
Interactive Effect ◽  
Accelerated Aging ◽  
Self And Other ◽  
Age Related ◽  
Negative Perceptions ◽  
The Individual ◽  
Age Range ◽  
Moderating Role ◽  
Age Awareness

Ageism has been associated with negative perceptions of the future and the aging process. The current study argues that this connection is affected by the relevance older adults attribute to the cognitive category of age in their own self-appraisal, as well as by how they perceive this awareness in others. Accordingly, we examined the association between ageism and subjective accelerated aging (i.e., the rate the individual feels he or she is aging) and the moderating role of self-age awareness and other-age awareness on this connection. Data were collected from 267 participants (age range = 40–95; M = 64.32, SD = 14.09), using scales assessing ageism, self/other age awareness, and subjective accelerated aging. High ageism levels were associated with increased subjective accelerated aging. Moreover, this connection was moderated by both self- and other-age awareness. The study enhances the importance of personal appraisals of one’s own and others’ behaviors as age-related in this context.

scholarly journals Childhood Adversity and Adult Health: The Role of Developmental Timing and Associations With Accelerated Aging

2018 ◽  
Vol 24 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Madelon M. E. Riem ◽  
Annemiek Karreman
Keyword(s):  
Accelerated Aging ◽  
Childhood Adversity ◽  
Adult Health ◽  
Fat Percentage ◽  
Childhood Experiences ◽  
Physical Problems ◽  
Age Related ◽  
Younger Age ◽  
Age Range

Childhood adversity has been associated with poor adult health. However, it is unclear whether timing of adversity matters in this association and whether adversity is related to poorer age-related physical health status. A representative sample of the adult Dutch population ( N = 3,586, age M = 54.94, age range = 18–92) completed surveys on health and diagnoses of age-related diseases. Information about weight and fat percentage was collected using weighing scales and childhood experiences were assessed retrospectively. Adversity was associated with higher body mass index and fat percentage, more physical problems, and high cholesterol, and this association was most pronounced in individuals with experiences of adversity during early adolescence. In addition, individuals with adversity more often reported physical problems or a medical diagnosis at a younger age. This study indicates that (1) timing of exposure to adversity matters in the relationship between experienced childhood adversity and health and (2) adversity is associated with a higher prevalence of age-related diseases at earlier ages.

scholarly journals Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice

2020 ◽  
Vol 10 (9) ◽  
pp. 583
Author(s):  
Patrick S. Hosford ◽  
Natalia Ninkina ◽  
Vladimir L. Buchman ◽  
Jeffrey C. Smith ◽  
Nephtali Marina ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Physiological Role ◽  
Normal Function ◽  
Whole Body ◽  
Cardiovascular Reflexes ◽  
Long Term Effects ◽  
Gene Encoding ◽  
Age Related

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.

scholarly journals Daily temperature cycles prolong lifespan and have sex-specific effects on peripheral clock gene expression in Drosophila melanogaster

2021 ◽  
pp. jeb.233213
Author(s):  
Grace H. Goh ◽  
Dominique Blache ◽  
Peter J. Mark ◽  
W. Jason Kennington ◽  
Shane K. Maloney
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Clock Gene ◽  
Clock Genes ◽  
Daily Temperature ◽  
Peripheral Tissues ◽  
Temperature Cycles ◽  
Clock Gene Expression ◽  
Age Related ◽  
Temperature Rhythms

Circadian rhythms optimize health by coordinating the timing of physiological processes to match predictable daily environmental challenges. The circadian rhythm of body temperature is thought to be an important modulator of molecular clocks in peripheral tissues, but how daily temperature cycles impact physiological function is unclear. Here, we examined the effect of constant (25°C, TCON) and cycling (28°C/22°C during light/dark, TCYC) temperature paradigms on lifespan of Drosophila melanogaster, and the expression of clock genes, Heat shock protein 83 (Hsp83), Frost (Fst), and Senescence-associated protein 30 (smp-30). Male and female Drosophila housed at TCYC had longer median lifespans than those housed at TCON. TCYC induced robust Hsp83 rhythms and rescued the age-related decrease in smp-30 expression that was observed in flies at TCON, potentially indicating an increased capacity to cope with age-related cellular stress. Ageing under TCON led to a decrease in the amplitude of expression of all clock genes in the bodies of male flies, except for cyc, which was non-rhythmic, and for per and cry in female flies. Strikingly, housing under TCYC conditions rescued the age-related decrease in amplitude of all clock genes, and generated rhythmicity in cyc expression, in the male flies, but not the female flies. The results suggest that ambient temperature rhythms modulate Drosophila lifespan, and that the amplitude of clock gene expression in peripheral body clocks may be a potential link between temperature rhythms and longevity in male Drosophila. Longevity due to TCYC appeared predominantly independent of clock gene amplitude in female Drosophila.

scholarly journals Big Lessons from Tiny Flies: Drosophila Melanogaster as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems

2018 ◽  
Author(s):  
Ameya Kasture ◽  
Thomas Hummel ◽  
Sonja Sucic ◽  
Michael Freissmuth
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Fate ◽  
Genetic Manipulation ◽  
Therapeutic Strategies ◽  
Proof Of Concept ◽  
Neuronal Connectivity ◽  
Genetic Tool ◽  
Human Orthologs ◽  
The Brain

The brain of Drosophila melanogaster is comprised of some 100,00 neurons, 127 and 80 of which are dopaminergic and serotonergic, respectively. Their activity regulates behavioral functions equivalent to those in mammals, e.g. motor activity, reward and aversion, memory formation, feeding, sexual appetite etc. Mammalian dopaminergic and serotonergic neurons are known to be heterogeneous. They differ in their projections and in their gene expression profile. A sophisticated genetic tool box is available, which allows for targeting virtually any gene with amazing precision in Drosophila melanogaster. Similarly, Drosophila genes can be replaced by their human orthologs including disease-associated alleles. Finally, genetic manipulation can be restricted to single fly neurons. This has allowed for addressing the role of individual neurons in circuits, which determine attraction and aversion, sleep and arousal, odor preference etc. Flies harboring mutated human orthologs provide models, which can be interrogated to understand the effect of the mutant protein on cell fate and neuronal connectivity. These models are also useful for proof-of-concept studies to examine the corrective action of therapeutic strategies. Finally, experiments in Drosophila can be readily scaled up to an extent, which allows for drug screening with reasonably high throughput.

scholarly journals dCubilin/dAMN- mediated protein reabsorption in Drosophila nephrocytes modulates longevity

2021 ◽  
Author(s):  
Xiaoming Feng ◽  
Xizhen Hong ◽  
Qiuxia Fan ◽  
Liting Chen ◽  
Jing Li ◽  
...  
Keyword(s):  
Aging Process ◽  
Whole Body ◽  
Genetic Enhancement ◽  
Neuronal Tissue ◽  
Age Related ◽  
Muscle Tissues ◽  
Protein Reabsorption ◽  
Cellular Pathways ◽  
Different Tissues

Aging is a multi-faceted process regulated by multiple cellular pathways, including the proteostasis network. Pharmacological or genetic enhancement of the intracellular proteostasis network extends lifespan and prevents age-related diseases. However, how proteostasis is regulated in different tissues throughout the aging process remains unclear. Here, we show that Drosophila homologs for Cubulin/Amnionless (dCubilin/dAMN)-mediated protein reabsorption from hemolymph (fly equivalent of blood) by nephrocytes modulates longevity through regulating proteostasis in muscle and brain tissues in Drosophila. We find that overexpression of dAMN receptor in nephrocytes extends lifespan, whereas nephrocyte-specific dCubilin or dAMN RNAi knockdown results in a protein reabsorption defect and shortens lifespan in flies. And we show that dCubilin/dAMN-mediated protein reabsorption in nephrocytes regulates proteostasis in hemolymph and improves healthspan. In addition, we show that enhanced dCubilin/dAMN-mediated protein reabsorption in nephrocytes slows down the aging process in muscle and brain by maintaining the proteostasis network in these tissues. Furthermore, our study shows that dCubilin/dAMN -mediated protein reabsorption in nephrocytes affects proteasome activity in the whole body and muscle tissues. Altogether, our work has revealed an inter-organ communication network across nephrocytes and muscle/neuronal tissue which is essential to maintain proteostasis and to delay senescence in these organs. The findings have provided insights into the role of renal protein reabsorption in the aging process via this tele-proteostasis network.

Oxidative stress and aging: Is methylglyoxal the hidden enemy?This review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 273-284 ◽  
Author(s):  
Kaushik M. Desai ◽  
Tuanjie Chang ◽  
Hui Wang ◽  
Ali Banigesh ◽  
Arti Dhar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Cellular Tissue ◽  
Cardiovascular Complications ◽  
Whole Body ◽  
Age Related ◽  
Transport Chain ◽  
Glycation End Products ◽  
Health And Disease

Aging is a multifactorial process that involves changes at the cellular, tissue, organ and the whole body levels resulting in decreased functioning, development of diseases, and ultimately death. Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases.

scholarly journals Mitochondrial Function, Mobility and Lifespan Are Improved in Drosophila melanogaster by Extracts of 9-cis-β-Carotene from Dunaliella salina

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 279 ◽  
Author(s):  
Tobias Weinrich ◽  
Yanan Xu ◽  
Chiziezi Wosu ◽  
Patricia J. Harvey ◽  
Glen Jeffery
Keyword(s):  
Drosophila Melanogaster ◽  
Mitochondrial Function ◽  
Dunaliella Salina ◽  
Whole Body ◽  
Biological Impact ◽  
Atp Production ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Age Related ◽  
Β Carotene

Carotenoids are implicated in alleviating ageing and age-related diseases in humans. While data from different carotenoids are mixed in their outcomes, those for 9-cis-β-carotene indicate general positive effects, although basic data on its biological impact are limited. Here, we show that supplementation with 9-cis-β-carotene in ageing Drosophila melanogaster improved mitochondrial function in terms of ATP production and whole-body respiration and extended mean lifespan. It also resulted in improved mobility. These data provide a potential biological rational for the beneficial effects of dietary supplementation with 9-cis-β-carotene. These effects may be based on the maintenance of a sound mitochondrial function.

scholarly journals NEURONAL-SPECIFIC PROTEASOME AUGMENTATION VIA EXTENDS LIFESPAN AND REDUCES AGE-RELATED NEURODEGENERATION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S96-S97
Author(s):  
Andrew M Pickering
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Nervous System ◽  
Drosophila Melanogaster ◽  
Stress Resistance ◽  
Brain Aging ◽  
Animal Kingdom ◽  
Age Related ◽  
And Function

Abstract Cognitive function declines with age throughout the animal kingdom and increasing evidence shows that disruption of the proteasome system contributes to this decline. The proteasome has important roles in multiple aspects of the nervous system, including synapse function and plasticity, as well as preventing cell death and senescence. We report that augmentation of proteasome function, using overexpression of the proteasome β5 subunit, enhances proteasome assembly and function. Significantly, we go on to show neuronal-specific proteasome augmentation slows age-related declines in measures of learning, memory, and circadian rhythmicity. Surprisingly neuronal specific proteasome augmentation of proteasome function also produces a robust increase of lifespan in Drosophila melanogaster. Our findings appear specific to the nervous system; ubiquitous proteasome overexpression increases oxidative stress resistance but does not impact lifespan and is detrimental to some healthspan measures. These findings demonstrate a key role of the proteasome system in brain aging.

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