Volume 5, Issue 10

Hooten NN, Fitzpatrick M, Wood WH, De S, Ejiogu N, Zhang Y, Mattison JA, Becker KG, Zonderman AB, Evans MK, . Age-related changes in microRNA levels in serum. . 5:725-740. https://doi.org/10.18632/aging.100603

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Hooten, Nicole Noren 
                AU  - Fitzpatrick, Megan 
                AU  - Wood, William H. 
                AU  - De, Supriyo 
                AU  - Ejiogu, Ngozi 
                AU  - Zhang, Yongqing 
                AU  - Mattison, Julie A. 
                AU  - Becker, Kevin G. 
                AU  - Zonderman, Alan B. 
                AU  - Evans, Michele K. 
                TI  - Age-related changes in microRNA levels in serum
                JO  - 
                JA  - 
                VL  - 5
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100603
                DO  - 10.18632/aging.100603
                SP  - 725
                EP  - 740
                PY  - 
                AB  - microRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by targeting specific mRNAs. Altered expression of circulating miRNAs have been associated with age-related diseases including cancer and cardiovascular disease. Although we and others have found an age-dependent decrease in miRNA expression in peripheral blood mononuclear cells (PBMCs), little is known about the role of circulating miRNAs in human aging. Here, we examined miRNA expression in human serum from young (mean age 30 years) and old (mean age 64 years) individuals using next generation sequencing technology and real-time quantitative PCR. Of the miRNAs that we found to be present in serum, three were significantly decreased in 20 older individuals compared to 20 younger individuals: miR-151a-5p, miR-181a-5p and miR-1248. Consistent with our data in humans, these miRNAs are also present at lower levels in the serum of elderly rhesus monkeys. In humans, miR-1248 was found to regulate the expression of mRNAs involved in inflammatory pathways and miR-181a was found to correlate negatively with the pro-inflammatory cytokines IL-6 and TNFα and to correlate positively with the anti-inflammatory cytokines TGFβ and IL-10. These results suggest that circulating miRNAs may be a biological marker of aging and could also be important for regulating longevity. Identification of stable miRNA biomarkers in serum could have great potential as a noninvasive diagnostic tool as well as enhance our understanding of physiological changes that occur with age.
                ER  -

Click to copy this citation from the text box above or download the citation:

TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants

Maruf H. Khan, Melissa Ligon, Lauren R. Hussey, Bryce Hufnal, Robert Farber II, Erin Munkácsy, Amanda Rodriguez, Andy Dillow, Erynn Kahlig, Shane L. Rea,

https://doi.org/10.18632/aging.100604 pp 741—758

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Khan MH, Ligon M, Hussey LR, Hufnal B, Farber R, Munkácsy E, Rodriguez A, Dillow A, Kahlig E, Rea SL, . TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. . 5:741-758. https://doi.org/10.18632/aging.100604

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Khan, Maruf H. 
                AU  - Ligon, Melissa 
                AU  - Hussey, Lauren R. 
                AU  - Hufnal, Bryce 
                AU  - Farber, Robert 
                AU  - Munkácsy, Erin 
                AU  - Rodriguez, Amanda 
                AU  - Dillow, Andy 
                AU  - Kahlig, Erynn 
                AU  - Rea, Shane L. 
                TI  - TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants
                JO  - 
                JA  - 
                VL  - 5
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100604
                DO  - 10.18632/aging.100604
                SP  - 741
                EP  - 758
                PY  - 
                AB  - While numerous life-extending manipulations have been discovered in the nematode Caenorhabditis elegans, one that remains most enigmatic is disruption of oxidative phosphorylation. In order to unravel how such an ostensibly deleterious manipulation can extend lifespan, we sought to identify the ensemble of nuclear transcription factors that are activated in response to defective mitochondrial electron transport chain (ETC) function. Using a feeding RNAi approach, we targeted over 400 transcription factors and identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors – AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)-interacting protein TAF-4 – were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF-1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.
                ER  -

Click to copy this citation from the text box above or download the citation:

A DNA synthesis inhibitor is protective against proteotoxic stressors via modulation of fertility pathways in Caenorhabditis elegans

Suzanne Angeli, Ida Klang, Renuka Sivapatham, Karla Mark, David Zucker, Dipa Bhaumik, Gordon J. Lithgow, Julie K. Andersen,

https://doi.org/10.18632/aging.100605 pp 759—769

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Angeli S, Klang I, Sivapatham R, Mark K, Zucker D, Bhaumik D, Lithgow GJ, Andersen JK, . A DNA synthesis inhibitor is protective against proteotoxic stressors via modulation of fertility pathways in Caenorhabditis elegans. . 5:759-769. https://doi.org/10.18632/aging.100605

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Angeli, Suzanne 
                AU  - Klang, Ida 
                AU  - Sivapatham, Renuka 
                AU  - Mark, Karla 
                AU  - Zucker, David 
                AU  - Bhaumik, Dipa 
                AU  - Lithgow, Gordon J. 
                AU  - Andersen, Julie K. 
                TI  - A DNA synthesis inhibitor is protective against proteotoxic stressors via modulation of fertility pathways in <i>Caenorhabditis elegans</i>
                JO  - 
                JA  - 
                VL  - 5
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100605
                DO  - 10.18632/aging.100605
                SP  - 759
                EP  - 769
                PY  - 
                AB  - Loss of germline precursor cells in C. elegans has previously been shown to improve protein homeostasis and extend lifespan, possibly due to reallocation of resources to somatic cells. In contrast, mutants that are sterile simply due to loss of sperm or oocyte production have a normal lifespan, often leading to the conclusion that loss of reproduction per se may have minor effects on C. elegans. We have found that inhibiting reproduction in C. elegans via the DNA synthesis inhibitor 5-fluoro-2-deoxyuridine (FUdR) improves protein homeostasis, stress resistance, and healthspan in wild-type animals. We find that FUdR is dependent on oogenesis and oocytic maturation. The effects of FUdR are dependent on FEM pathways, which regulate initiation of spermatogenesis. Loss of FEM expression leads to feminized animals that maintain arrested oocytes and are refractory to the effects of FUdR. FUdR-dependence is restored by spermatogenic signals, which trigger oocytic maturation and ovulation. Further, loss of FEM-3, a novel protein required for spermatogenesis, is sufficient to improve aspects of proteostasis. These effects are independent of previously described germline signals, including the DAF-16/FOXO, DAF-12/VDR, and HSF-1 pathways. These findings suggest that genetic or chemical inhibition of oocyte production can improve protein homeostasis in C. elegans.
                ER  -

Click to copy this citation from the text box above or download the citation:

PP2A inhibition results in hepatic insulin resistance despite Akt2 activation

Thomas Galbo, Rachel J. Perry, Erica Nishimura, Varman T. Samuel, Bjørn Quistorff, Gerald I. Shulman,

https://doi.org/10.18632/aging.100611 pp 770—781

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Galbo T, Perry RJ, Nishimura E, Samuel VT, Quistorff B, Shulman GI, . PP2A inhibition results in hepatic insulin resistance despite Akt2 activation. . 5:770-781. https://doi.org/10.18632/aging.100611

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Galbo, Thomas 
                AU  - Perry, Rachel J. 
                AU  - Nishimura, Erica 
                AU  - Samuel, Varman T. 
                AU  - Quistorff, Bjørn 
                AU  - Shulman, Gerald I. 
                TI  - PP2A inhibition results in hepatic insulin resistance despite Akt2 activation
                JO  - 
                JA  - 
                VL  - 5
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100611
                DO  - 10.18632/aging.100611
                SP  - 770
                EP  - 781
                PY  - 
                AB  - In the liver, insulin suppresses hepatic gluconeogenesis by activating Akt, which inactivates the key gluconeogenic transcription factor FoxO1 (Forkhead Box O1). Recent studies have implicated hyperactivity of the Akt phosphatase Protein Phosphatase 2A (PP2A) and impaired Akt signaling as a molecular defect underlying insulin resistance. We therefore hypothesized that PP2A inhibition would enhance insulin-stimulated Akt activity and decrease glucose production. PP2A inhibitors increased hepatic Akt phosphorylation and inhibited FoxO1 in vitro and in vivo, and suppressed gluconeogenesis in hepatocytes. Paradoxically, PP2A inhibition exacerbated insulin resistance in vivo. This was explained by phosphorylation of both hepatic glycogen synthase (GS) (inactivation) and phosphorylase (activation) resulting in impairment of glycogen storage. Our findings underline the significance of GS and Phosphorylase as hepatic PP2A substrates and importance of glycogen metabolism in acute plasma glucose regulation.
                ER  -

Click to copy this citation from the text box above or download the citation:

Aging on a different scale – chronological versus pathology-related aging

Joost P.M. Melis, Martijs J. Jonker, Jan Vijg, Jan H.J. Hoeijmakers, Timo M. Breit, Harry van Steeg,

https://doi.org/10.18632/aging.100606 pp 782—788

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Melis JP, Jonker MJ, Vijg J, Hoeijmakers JH, Breit TM, van Steeg H, . Aging on a different scale – chronological versus pathology-related aging. . 5:782-788. https://doi.org/10.18632/aging.100606

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Melis, Joost P.M. 
                AU  - Jonker, Martijs J. 
                AU  - Vijg, Jan 
                AU  - Hoeijmakers, Jan H.J. 
                AU  - Breit, Timo M. 
                AU  - van Steeg, Harry 
                TI  - Aging on a different scale – chronological versus pathology-related aging
                JO  - 
                JA  - 
                VL  - 5
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100606
                DO  - 10.18632/aging.100606
                SP  - 782
                EP  - 788
                PY  - 
                AB  - In the next decades the elderly population will increase dramatically, demanding appropriate solutions in health care and aging research focusing on healthy aging to prevent high burdens and costs in health care. For this, research targeting tissue-specific and individual aging is paramount to make the necessary progression in aging research. In a recently published study we have attempted to make a step interpreting aging data on chronological as well as pathological scale. For this, we sampled five major tissues at regular time intervals during the entire C57BL/6J murine lifespan from a controlled in vivo aging study, measured the whole transcriptome and incorporated temporal as well as physical health aspects into the analyses. In total, we used 18 different age-related pathological parameters and transcriptomic profiles of liver, kidney, spleen, lung and brain and created a database that can now be used for a broad systems biology approach. In our study, we focused on the dynamics of biological processes during chronological aging and the comparison between chronological and pathology-related aging.
                ER  -

Click to copy this citation from the text box above or download the citation:

Volume 5, Issue 10

Editorials

ΔNp53 and aging

Shih-Chieh Lin, Dylan J. Taatjes,

Epigenetic aging: insights from network biology

Andrew E. Teschendorff,

microRNA biogenesis and senescence

Daniel Gómez-Cabello, Isabel Adrados, Ignacio Palmero,

Repression of GH signaling: One extended life to live!

Darlene E. Berryman, Edward O. List, John J. Kopchick,

Research Papers

Age-related changes in microRNA levels in serum

Nicole Noren Hooten, Megan Fitzpatrick, William H. Wood 3rd, Supriyo De, Ngozi Ejiogu, Yongqing Zhang, Julie A. Mattison, Kevin G. Becker, Alan B. Zonderman, Michele K. Evans,

TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants

Maruf H. Khan, Melissa Ligon, Lauren R. Hussey, Bryce Hufnal, Robert Farber II, Erin Munkácsy, Amanda Rodriguez, Andy Dillow, Erynn Kahlig, Shane L. Rea,

A DNA synthesis inhibitor is protective against proteotoxic stressors via modulation of fertility pathways in Caenorhabditis elegans

Suzanne Angeli, Ida Klang, Renuka Sivapatham, Karla Mark, David Zucker, Dipa Bhaumik, Gordon J. Lithgow, Julie K. Andersen,

PP2A inhibition results in hepatic insulin resistance despite Akt2 activation

Thomas Galbo, Rachel J. Perry, Erica Nishimura, Varman T. Samuel, Bjørn Quistorff, Gerald I. Shulman,

Research Perspective

Aging on a different scale – chronological versus pathology-related aging

Joost P.M. Melis, Martijs J. Jonker, Jan Vijg, Jan H.J. Hoeijmakers, Timo M. Breit, Harry van Steeg,

Explore This Issue