Is there a link between aging and microbiome diversity in exceptional mammalian longevity?

A changing microbiome has been linked to biological aging in mice and humans, suggesting a possible role of gut flora in pathogenic aging phenotypes. Many bat species have exceptional longevity given their body size and some can live up to ten times longer than expected with little signs of aging. This study explores the anal microbiome of the exceptionally long-lived Myotis myotis bat, investigating bacterial composition in both adult and juvenile bats to determine if the microbiome changes with age in a wild, long-lived non-model organism, using non-lethal sampling. The anal microbiome was sequenced using metabarcoding in more than 50 individuals, finding no significant difference between the composition of juvenile and adult bats, suggesting that age-related microbial shifts previously observed in other mammals may not be present in Myotis myotis. Functional gene categories, inferred from metabarcoding data, expressed in the M. myotis microbiome were categorized identifying pathways involved in metabolism, DNA repair and oxidative phosphorylation. We highlight an abundance of ‘Proteobacteria’ relative to other mammals, with similar patterns compared to other bat microbiomes. Our results suggest that M. myotis may have a relatively stable, unchanging microbiome playing a role in their extended ‘health spans’ with the advancement of age, and suggest a potential link between microbiome and sustained, powered flight.

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Deciphering the microRNA transcriptome of skeletal muscle during porcine development

PeerJ ◽

10.7717/peerj.1504 ◽

2016 ◽

Vol 4 ◽

pp. e1504 ◽

Cited By ~ 8

Author(s):

Miaomiao Mai ◽

Long Jin ◽

Shilin Tian ◽

Rui Liu ◽

Wenyao Huang ◽

...

Keyword(s):

Muscle Development ◽

Model Organism ◽

Muscle Disease ◽

Porcine Muscle ◽

Development Stages ◽

Age Related ◽

Series Expression ◽

Pig Muscle ◽

Short Time

MicroRNAs (miRNAs) play critical roles in many important biological processes, such as growth and development in mammals. Various studies of porcine muscle development have mainly focused on identifying miRNAs that are important for fetal and adult muscle development; however, little is known about the role of miRNAs in middle-aged muscle development. Here, we present a comprehensive investigation of miRNA transcriptomes across five porcine muscle development stages, including one prenatal and four postnatal stages. We identified 404 known porcine miRNAs, 118 novel miRNAs, and 101 miRNAs that are conserved in other mammals. A set of universally abundant miRNAs was found across the distinct muscle development stages. This set of miRNAs may play important housekeeping roles that are involved in myogenesis. A short time-series expression miner analysis indicated significant variations in miRNA expression across distinct muscle development stages. We also found enhanced differentiation- and morphogenesis-related miRNA levels in the embryonic stage; conversely, apoptosis-related miRNA levels increased relatively later in muscle development. These results provide integral insight into miRNA function throughout pig muscle development stages. Our findings will promote further development of the pig as a model organism for human age-related muscle disease research.

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Role of CheB and CheR in the Complex Chemotactic and Aerotactic Pathway of Azospirillum brasilense

Journal of Bacteriology ◽

10.1128/jb.00267-06 ◽

2006 ◽

Vol 188 (13) ◽

pp. 4759-4768 ◽

Cited By ~ 31

Author(s):

Bonnie B. Stephens ◽

Star N. Loar ◽

Gladys Alexandre

Keyword(s):

Escherichia Coli ◽

Steady State ◽

Azospirillum Brasilense ◽

Model Organism ◽

Spatial Gradient ◽

Wild Type ◽

Temporal Gradient ◽

E Coli ◽

Significant Difference

ABSTRACT It has previously been reported that the alpha-proteobacterium Azospirillum brasilense undergoes methylation-independent chemotaxis; however, a recent study revealed cheB and cheR genes in this organism. We have constructed cheB, cheR, and cheBR mutants of A. brasilense and determined that the CheB and CheR proteins under study significantly influence chemotaxis and aerotaxis but are not essential for these behaviors to occur. First, we found that although cells lacking CheB, CheR, or both were no longer capable of responding to the addition of most chemoattractants in a temporal gradient assay, they did show a chemotactic response (albeit reduced) in a spatial gradient assay. Second, in comparison to the wild type, cheB and cheR mutants under steady-state conditions exhibited an altered swimming bias, whereas the cheBR mutant and the che operon mutant did not. Third, cheB and cheR mutants were null for aerotaxis, whereas the cheBR mutant showed reduced aerotaxis. In contrast to the swimming bias for the model organism Escherichia coli, the swimming bias in A. brasilense cells was dependent on the carbon source present and cells released methanol upon addition of some attractants and upon removal of other attractants. In comparison to the wild type, the cheB, cheR, and cheBR mutants showed various altered patterns of methanol release upon exposure to attractants. This study reveals a significant difference between the chemotaxis adaptation system of A. brasilense and that of the model organism E. coli and suggests that multiple chemotaxis systems are present and contribute to chemotaxis and aerotaxis in A. brasilense.

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Mitochondria and Aging—The Role of Exercise as a Countermeasure

Biology ◽

10.3390/biology8020040 ◽

2019 ◽

Vol 8 (2) ◽

pp. 40 ◽

Cited By ~ 17

Author(s):

Mats I Nilsson ◽

Mark A Tarnopolsky

Keyword(s):

Reactive Oxygen Species Generation ◽

Biological Aging ◽

Primary Role ◽

Oxygen Species ◽

Vicious Cycle ◽

Life And Death ◽

Cell Functions ◽

Age Related ◽

Damage Protein

Mitochondria orchestrate the life and death of most eukaryotic cells by virtue of their ability to supply adenosine triphosphate from aerobic respiration for growth, development, and maintenance of the ‘physiologic reserve’. Although their double-membrane structure and primary role as ‘powerhouses of the cell’ have essentially remained the same for ~2 billion years, they have evolved to regulate other cell functions that contribute to the aging process, such as reactive oxygen species generation, inflammation, senescence, and apoptosis. Biological aging is characterized by buildup of intracellular debris (e.g., oxidative damage, protein aggregates, and lipofuscin), which fuels a ‘vicious cycle’ of cell/DNA danger response activation (CDR and DDR, respectively), chronic inflammation (‘inflammaging’), and progressive cell deterioration. Therapeutic options that coordinately mitigate age-related declines in mitochondria and organelles involved in quality control, repair, and recycling are therefore highly desirable. Rejuvenation by exercise is a non-pharmacological approach that targets all the major hallmarks of aging and extends both health- and lifespan in modern humans.

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Age-related loss of SirT1 expression results in dysregulated human vascular smooth muscle cell function

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00871.2013 ◽

2014 ◽

Vol 307 (4) ◽

pp. H533-H541 ◽

Cited By ~ 43

Author(s):

Anne Marie Thompson ◽

Robert Wagner ◽

Eva M. Rzucidlo

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Vascular Smooth Muscle Cell ◽

Cellular Migration ◽

Sirt1 Expression ◽

Age Related ◽

Significant Difference

Loss of vascular smooth muscle cell (VSMC) function is a hallmark of vascular disease. VSMCs become increasingly dysregulated, apoptotic, and senescent as we age. Sirtuin 1 (SirT1) is a deactylase that regulates substrates associated with stress mitigation, metabolism, and aging. Our aim was to examine the role of SirT1 in vascular aging and the function this protein plays in the context of cellular response to stress and senescence. We compared endogenous SirT1 expression in young and old human donors. Human VSMC (HuVSMC) from donors ranging in age from 12 to 88 ( n = 14) were isolated and cultured. In cultured HuVSMC the levels of endogenous SirT1 were examined by Western blot analysis. We found that endogenous SirT1 protein expression inversely correlated with donor age. Additionally, we demonstrated that age-related loss of SirT1 correlated in functional deficits, diminished stress response, reduced capacity for migration, and proliferation and increased senescence. Manipulation of SirT1 levels in young cells confirmed the role of SirT1 in cellular migration and proliferation capability. Furthermore, we demonstrated that age-related loss of SirT1 was associated with the induction of VSMC senescence. With correlation to symptomatic disease, we demonstrated a significant difference in SirT1 levels from HuVSMC isolated from aged arteries that were occluded with atherosclerotic lesions ( n = 7), compared with patent sections of the same artery. Having demonstrated that endogenous SirT1 is lost with age, which correlates with a loss of capacity for vascular repair, our data explain one of the molecular changes that occurs in the aged vasculature.

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Varicocele treatment: A 2-centers comparison between non microsurgical open correction, laparoscopic approach and retrograde percutaneous sclerotization on 463 cases

Archivio Italiano di Urologia e Andrologia ◽

10.4081/aiua.2013.3.143 ◽

2013 ◽

Vol 85 (3) ◽

pp. 143 ◽

Cited By ~ 1

Author(s):

Giangiacomo Ollandini ◽

Giovanni Liguori ◽

Stanislav Ziaran ◽

Tomáš Málek ◽

Giorgio Mazzon ◽

...

Keyword(s):

Sperm Count ◽

Laparoscopic Approach ◽

Sperm Parameters ◽

Age Related ◽

Number Of Patients ◽

Significant Difference ◽

Bivariate Regression ◽

Open Surgical Procedure ◽

Bivariate Regression Analysis

Objectives: To determine whether there are differences in sperm parameters improvement after different varicocele correction techniques. To determine the role of age in sperm parameters improvement. Methods: 2 different European centers collected pre- and postoperative sperm parameters of patients undergoing varicocele correction. Among 463 evaluated patients, 367 were included. Patients were divided in procedure-related and age-related groups. Ivanissevich inguinal open surgical procedure (OS), lymphatic-sparing laparoscopic approach (LSL) and retrograde percutaneous transfemoral sclerotization (RPS) were performed. As outcome measurements sperm count (millions/mL, SC) and percentage of mobile sperms were analyzed. Univariate and multivariate regression between the defined groups; bivariate regression analysis between age and sperm count and motility. Results: Number of patients: OS 78; LSL 85; RPS 204. Mean age 30.2 (SD 6.83); postoperative SC increased from 18.2 to 30.1 (CI 95% 27.3-32.9; p < 0,001); motility from 25.6 to 32.56% (30.9-34.2; p < 0.001). OS: SC varied from 16.9 to 18.2 (p < 0.001); sperm motility from 29% to 33% (p < 0.001). LSL: SC from 15.5 to 17.2 (p < 0.001); motility from 27 to 31% (p < 0.001). RPS: SC from 18.9 to 36.2 (p < 0.001); motility from 24% to 32% (p < 0.001). Univariate and multivariate analysis confirmed the significant difference of SC variation in RPS, compared to the other groups (p < 0.001). No significance between LSL and OS (p = 0.826). No significant differences regarding motility (p = 0.8). Conclusions: Varicocele correction is confirmed useful in improving sperm parameters; sclerotization technique leads to a better sperm improvement compared to other studied procedures; improvement in seminal parameters is not affected by age of the patients treated.

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Nrf2 activation induces mitophagy and reverses Parkin/Pink1 knock down-mediated neuronal and muscle degeneration phenotypes

Cell Death and Disease ◽

10.1038/s41419-021-03952-w ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Sentiljana Gumeni ◽

Eleni-Dimitra Papanagnou ◽

Maria S. Manola ◽

Ioannis P. Trougakos

Keyword(s):

Critical Role ◽

Model Organism ◽

Dependent Manner ◽

Degenerative Diseases ◽

Knock Down ◽

Age Related ◽

Degenerative Disorders ◽

Pathway Activation

AbstractThe balanced functionality of cellular proteostatic modules is central to both proteome stability and mitochondrial physiology; thus, the age-related decline of proteostasis also triggers mitochondrial dysfunction, which marks multiple degenerative disorders. Non-functional mitochondria are removed by mitophagy, including Parkin/Pink1-mediated mitophagy. A common feature of neuronal or muscle degenerative diseases, is the accumulation of damaged mitochondria due to disrupted mitophagy rates. Here, we exploit Drosophila as a model organism to investigate the functional role of Parkin/Pink1 in regulating mitophagy and proteostatic responses, as well as in suppressing degenerative phenotypes at the whole organism level. We found that Parkin or Pink1 knock down in young flies modulated proteostatic components in a tissue-dependent manner, increased cell oxidative load, and suppressed mitophagy in neuronal and muscle tissues, causing mitochondrial aggregation and neuromuscular degeneration. Concomitant to Parkin or Pink1 knock down cncC/Nrf2 overexpression, induced the proteostasis network, suppressed oxidative stress, restored mitochondrial function, and elevated mitophagy rates in flies’ tissues; it also, largely rescued Parkin or Pink1 knock down-mediated neuromuscular degenerative phenotypes. Our in vivo findings highlight the critical role of the Parkin/Pink1 pathway in mitophagy, and support the therapeutic potency of Nrf2 (a druggable pathway) activation in age-related degenerative diseases.

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Sexually divergent DNA methylation programs with hippocampal aging

10.1101/161752 ◽

2017 ◽

Cited By ~ 2

Author(s):

Dustin R. Masser ◽

Niran Hadad ◽

Hunter Porter ◽

Colleen A. Mangold ◽

Archana Unnikrishnan ◽

...

Keyword(s):

Dna Methylation ◽

Sex Differences ◽

Biological Aging ◽

Age Related ◽

Genome Wide ◽

Aging Response ◽

Genomic Location ◽

Methylation Patterns ◽

Genomic Methylation

SummaryDNA methylation is a central regulator of genome function and altered methylation patterns are indicative of biological aging and mortality. Age-related cellular, biochemical, and molecular changes in the hippocampus lead to cognitive impairments and greater vulnerability to neurodegenerative disease that varies between the sexes. The role of hippocampal epigenomic changes with aging in these processes is unknown as no genome-wide analyses of age-related methylation changes have considered the factor of sex in a controlled animal model. High-depth, genome-wide bisulfite sequencing of young (3 month) and old (24 month) male and female mouse hippocampus revealed that while total genomic methylation amounts did not change with aging, specific sites in CG and non-CG (CH) contexts demonstrated age-related increases or decreases in methylation that were predominantly sexually divergent. Differential methylation with age for both CG and CH sites was enriched in intergenic, and intronic regions and under-represented in promoters, CG islands and specific enhancer regions in both sexes suggesting that certain genomic elements are especially labile with aging, even if the exact genomic loci altered are predominantly sex-specific. Life-long sex differences in autosomal methylation at CG and CH sites were also observed. The lack of genome-wide hypomethylation, sexually divergent aging response, and autosomal sex differences at CG sites were confirmed in human data. These data reveal sex as a previously unappreciated central factor of hippocampal epigenomic changes with aging. In total, these data demonstrate an intricate regulation of DNA methylation with aging by sex, cytosine context, genomic location, and methylation level.

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SPERMIDINE MAINTAINS TELOMERE LENGTH AND DELAYS AGING

Central Asian Journal of Medical Hypotheses and Ethics ◽

10.47316/cajmhe.2021.2.1.08 ◽

2021 ◽

Vol 2 (1) ◽

pp. 51-58

Author(s):

Priyanka Sharma ◽

Rishi Kumar Jaiswal

Keyword(s):

Telomere Length ◽

Human Population ◽

Cellular Level ◽

Telomere Maintenance ◽

Cellular Processes ◽

Intracellular Calcium Signaling ◽

Age Related ◽

Aging Properties ◽

Potential Link

Spermidine, a natural polyamine, has been noticed for its anti-aging properties. Supplementation of this drug prolongs lifespan and diminishes the incidence of age-related pathology. In the human population, spermidine levels decrease as aging progresses, and a potential link between diminished endogenous spermidine levels and age-related declination has been studied. At the cellular level, autophagy is the prime mode of action of spermidine known to decline with the progress of aging, similarly contributing to the accretion of impaired macromolecules and organelles through aging. Epidemiological statistics support the concept, suggesting that elevated uptake of polyamine delays aging. Here, we overview the effect of autophagy on cellular processes and age-associated diseases, emphasizing the importance of these events to the hallmarks of aging. There are numerous factors like shortening telomere, oxidative stress, mitochondrial damage, and impaired intracellular calcium signaling, which are influenced by the aging process. We hypothesize that spermidine supplements in the diet increase the telomere length. The proposed hypothesis also brings to light the differentially regulated genes involved in telomere maintenance and aging after spermidine treatment. Knowing the role of spermidine in telomere maintenance would help us understand the molecular mechanism of spermidine's effect on aging.

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UNDERSTANDING THE ROLE OF STRESS PROCESSES IN CUMULATIVE DIS/ADVANTAGE PROCESSES

Innovation in Aging ◽

10.1093/geroni/igz038.1562 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S418-S418

Author(s):

Deborah Carr

Keyword(s):

Life Course ◽

Functional Limitations ◽

Later Life ◽

Well Being ◽

The United States ◽

Poor Quality ◽

Process Models ◽

Biological Aging ◽

Age Related

Abstract In my book Golden Years (2019), I argue that the psychosocial consequences of normal biological processes of aging are intensified for those who have had lives of disadvantage, just as the harmful consequences of life-course disadvantages are particularly acute for those experiencing age-related physical health declines. In this paper, I discuss the role of stress processes, including stress proliferation and amplification, as possible mechanisms contributing to cumulative dis/advantage. I evaluate these ideas empirically by focusing on the linkages between functional limitations (an indicator of normal biological aging) and psychological well-being in later life, and explore the extent to which these linkages are amplified diverse indicators of life course disadvantage including low education; poor-quality employment; avoidant coping strategies; and family-related strains including intensive caregiving. Analyses are based on data from the Midlife in the United States (MIDUS) study. I discuss the implications of incorporating stress process models in cumulative dis/advantage research.

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Chronically III Hospitalized Children's Concepts of Their Illness

PEDIATRICS ◽

10.1542/peds.69.3.355 ◽

1982 ◽

Vol 69 (3) ◽

pp. 355-362

Author(s):

Arlene B. Brewster

Keyword(s):

Medical Staff ◽

Conceptual Development ◽

Chronically Ill ◽

Human Action ◽

Medical Procedures ◽

Staff Members ◽

Age Related ◽

Significant Difference ◽

The Relationship

This study investigates the relationship between cognitive development and children's understanding of the cause of illness, intent of medical procedures, and role of the medical staff. A group of 50, chronically ill hospitalized children of normal IQ, aged 5 to 12 years, was given five tasks, scored in ascending order of cognitive maturation. Results indicated a correlation coefficient of responses (P <.01) among tasks. Analysis of variance yielded an age-related maturation of responses (P <.01). No significant difference in level of response beween high and low affect tasks was found. There was a three-stage sequence of conceptual development in understanding cause of illness: (1) illness is caused by human action; (2) illness is caused by germs; (3) illness is caused by physical weakness or susceptibility. A parallel three-stage sequence of understanding of the intent of medical procedures was discerned: (1) the child views procedures as punishment; (2) he/she correctly perceives the procedures, but believes that the staffs empathy depends on the patient's expressing pain; (3) the child can infer both intention and empathy from the medical staff. Specific illness, sex of the child, and length of hospitalization did not affect the child's level of response. Children process information about their illnesses through a predictable maturational cognitive sequence which medical staff members must address for comprehension to occur.

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