The Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences

Alonso, Ana; Fernández, Rebeca; Moreno, María; Ordóñez, Patricia; González-Pardo, Héctor; Conejo, Nélida M.; Díaz, Fernando; González, Celestino

doi: 10.1093/gerona/61.5.419pmid: 16720737

Aging is associated with insulin resistance, which represents a common factor in age-related diseases. We aimed to determine the role of 17β-estradiol on insulin sensitivity and memory during aging using ovariectomized rats (2–26 months of age) treated with physiological doses of 17β-estradiol. Our results indicate a lack of effect of 17β-estradiol replacement on spatial memory assessed in a water maze. Conversely, estradiol treatment improved insulin sensitivity in aging rats. These data imply that relatively low doses of 17β-estradiol may have beneficial effects on glucose homeostasis due to the protective effects of estrogen. However, estradiol treatment used in the present study did not prevent memory impairment associated with aging.

Ana Alonso, Rebeca Fernández, María Moreno, Patricia Ordóñez, Héctor González-Pardo, Nélida M. Conejo, Fernando Díaz, Celestino González

doi: biomedgerontology;61/5/419pmid: N/A

Aging is associated with insulin resistance, which represents a common factor in age-related diseases. We aimed to determine the role of 17β-estradiol on insulin sensitivity and memory during aging using ovariectomized rats (2–26 months of age) treated with physiological doses of 17β-estradiol. Our results indicate a lack of effect of 17β-estradiol replacement on spatial memory assessed in a water maze. Conversely, estradiol treatment improved insulin sensitivity in aging rats. These data imply that relatively low doses of 17β-estradiol may have beneficial effects on glucose homeostasis due to the protective effects of estrogen. However, estradiol treatment used in the present study did not prevent memory impairment associated with aging. The Gerontological Society of America « Previous | Next Article » Table of Contents This Article J Gerontol A Biol Sci Med Sci (2006) 61 (5): 419-426. » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Journal of Gerontology: Biological Sciences Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Alonso, A. Articles by González, C. Search for related content PubMed PubMed citation Articles by Alonso, A. Articles by Fernández, R. Articles by Moreno, M. Articles by Ordóñez, P. Articles by González-Pardo, H. Articles by Conejo, N. M. Articles by Díaz, F. Articles by González, C. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue November 2015 70 (11) Alert me to new issues The Journal About the journal Translational Articles Free Editors’ Choice Articles Impact Factor Articles The Journals of Gerontology, Series A Supplements Special Issues Rights & permissions We are mobile – find out more Journal Career Network Published on behalf of The Gerontological Society of America Impact Factor: 5.416 5-Yr impact factor: 5.406 Editorial Boards The Journals of Gerontology, Series A: Biological Sciences Rafael de Cabo, PhD, Editor View full editorial board The Journals of Gerontology, Series A: Medical Sciences Stephen B. Kritchevsky, PhD View full editorial board For the Media GSA Press Room For Authors Instructions to authors Services for authors Submit Now: Biological Sciences Submit Now: Medical Sciences Self-Archiving Policy Online Submission Open access options for authors - visit Oxford Open WhsSvhnOkaAwYG81FJCYgwG7z1LnIP2F true Looking for your next opportunity? Looking for jobs... jQuery_1_11 = jQuery.noConflict(true); Corporate Services What we offer Advertising sales Reprints Supplements Classified Advertising Sales Alerting Services Email table of contents CiteTrack XML RSS feed

Alonso, Ana; Fernández, Rebeca; Moreno, María; Ordóñez, Patricia; González-Pardo, Héctor; Conejo, Nélida M.; Díaz, Fernando; González, Celestino

doi: N/Apmid: N/A

Aging is associated with insulin resistance, which represents a common factor in age-related diseases. We aimed to determine the role of 17β-estradiol on insulin sensitivity and memory during aging using ovariectomized rats (2–26 months of age) treated with physiological doses of 17β-estradiol. Our results indicate a lack of effect of 17β-estradiol replacement on spatial memory assessed in a water maze. Conversely, estradiol treatment improved insulin sensitivity in aging rats. These data imply that relatively low doses of 17β-estradiol may have beneficial effects on glucose homeostasis due to the protective effects of estrogen. However, estradiol treatment used in the present study did not prevent memory impairment associated with aging.

Cabelof, Diane C.; Raffoul, Julian J.; Ge, Yubin; Van Remmen, Holly; Matherly, Larry H.; Heydari, Ahmad R.

doi: N/Apmid: N/A

Young (4- to 6-month-old) and aged (24- to 28-month-old) mice were exposed to 2-nitropropane (2-NP), a DNA oxidizing agent, and the ability to induce DNA polymerase β (β-pol) and AP endonuclease (APE) was determined. In contrast to the inducibility of these gene products in response to oxidative damage in young mice, aged mice showed a lack of inducibility of β-pol and APE. APE protein level and endonuclease activity were both reduced 40% (p <.01) in response to 2-NP. Accordingly, the accumulation of DNA repair intermediates in response to 2-NP differed with age. Young animals accumulated 3′OH-containing DNA strand breaks, whereas the aged animals did not. A role for p53 in the difference in DNA damage response with age is suggested by the observation that the accumulation of p53 protein in response to DNA damage in young animals was absent in the aged animals. Our results are consistent with a reduced ability to process DNA damage with age.

Diane C. Cabelof, Julian J. Raffoul, Yubin Ge, Holly Van Remmen, Larry H. Matherly, Ahmad R. Heydari

doi: biomedgerontology;61/5/427pmid: N/A

Young (4- to 6-month-old) and aged (24- to 28-month-old) mice were exposed to 2-nitropropane (2-NP), a DNA oxidizing agent, and the ability to induce DNA polymerase β (β-pol) and AP endonuclease (APE) was determined. In contrast to the inducibility of these gene products in response to oxidative damage in young mice, aged mice showed a lack of inducibility of β-pol and APE. APE protein level and endonuclease activity were both reduced 40% ( p <.01) in response to 2-NP. Accordingly, the accumulation of DNA repair intermediates in response to 2-NP differed with age. Young animals accumulated 3′OH-containing DNA strand breaks, whereas the aged animals did not. A role for p53 in the difference in DNA damage response with age is suggested by the observation that the accumulation of p53 protein in response to DNA damage in young animals was absent in the aged animals. Our results are consistent with a reduced ability to process DNA damage with age. The Gerontological Society of America « Previous | Next Article » Table of Contents This Article J Gerontol A Biol Sci Med Sci (2006) 61 (5): 427-434. » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Journal of Gerontology: Biological Sciences Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Cabelof, D. C. Articles by Heydari, A. R. Search for related content PubMed PubMed citation Articles by Cabelof, D. C. Articles by Raffoul, J. J. Articles by Ge, Y. Articles by Van Remmen, H. Articles by Matherly, L. H. Articles by Heydari, A. R. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue November 2015 70 (11) Alert me to new issues The Journal About the journal Translational Articles Free Editors’ Choice Articles Impact Factor Articles The Journals of Gerontology, Series A Supplements Special Issues Rights & permissions We are mobile – find out more Journal Career Network Published on behalf of The Gerontological Society of America Impact Factor: 5.416 5-Yr impact factor: 5.406 Editorial Boards The Journals of Gerontology, Series A: Biological Sciences Rafael de Cabo, PhD, Editor View full editorial board The Journals of Gerontology, Series A: Medical Sciences Stephen B. Kritchevsky, PhD View full editorial board For the Media GSA Press Room For Authors Instructions to authors Services for authors Submit Now: Biological Sciences Submit Now: Medical Sciences Self-Archiving Policy Online Submission Open access options for authors - visit Oxford Open WhsSvhnOkaAwYG81FJCYgwG7z1LnIP2F true Looking for your next opportunity? Looking for jobs... jQuery_1_11 = jQuery.noConflict(true); Corporate Services What we offer Advertising sales Reprints Supplements Classified Advertising Sales Alerting Services Email table of contents CiteTrack XML RSS feed

Cabelof, Diane C.; Raffoul, Julian J.; Ge, Yubin; Van Remmen, Holly; Matherly, Larry H.; Heydari, Ahmad R.

doi: 10.1093/gerona/61.5.427pmid: 16720738

Young (4- to 6-month-old) and aged (24- to 28-month-old) mice were exposed to 2-nitropropane (2-NP), a DNA oxidizing agent, and the ability to induce DNA polymerase β (β-pol) and AP endonuclease (APE) was determined. In contrast to the inducibility of these gene products in response to oxidative damage in young mice, aged mice showed a lack of inducibility of β-pol and APE. APE protein level and endonuclease activity were both reduced 40% (p <.01) in response to 2-NP. Accordingly, the accumulation of DNA repair intermediates in response to 2-NP differed with age. Young animals accumulated 3′OH-containing DNA strand breaks, whereas the aged animals did not. A role for p53 in the difference in DNA damage response with age is suggested by the observation that the accumulation of p53 protein in response to DNA damage in young animals was absent in the aged animals. Our results are consistent with a reduced ability to process DNA damage with age.

Richard R. Erickson, Lisa M. Dunning, Jordan L. Holtzman

doi: biomedgerontology;61/5/435pmid: N/A

The endoplasmic reticulum (ER) chaperones are highly conserved proteins that catalyze the posttranslational processing of all secretory and membrane proteins. Our studies suggest that chaperone declines are one of the two central defects in Alzheimer's disease. We propose that similar declines in other organ systems underlie the physiological deficits of aging. Rats were maintained in a colony from age 21 days to death. Animals were killed at regular intervals, and hepatic, ER chaperone contents were determined by immunoblotting. ERp55, ERp57, ERp72, BiP, and calnexin constitutive levels declined 30%–50% with age. Calreticulin was unaffected. BiP (also known as GRP78), ERp55, and ERp57 showed marked swings with peaks occurring in midwinter and midsummer. This cyclics declined 73% with age. Considering the role of the ER chaperones in membrane and secretory protein posttranslational processing, these data support the concept that their loss could lead to many of the physiological declines associated with aging. The Gerontological Society of America « Previous | Next Article » Table of Contents This Article J Gerontol A Biol Sci Med Sci (2006) 61 (5): 435-443. » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Journal of Gerontology: Biological Sciences Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Erickson, R. R. Articles by Holtzman, J. L. Search for related content PubMed PubMed citation Articles by Erickson, R. R. Articles by Dunning, L. M. Articles by Holtzman, J. L. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue November 2015 70 (11) Alert me to new issues The Journal About the journal Translational Articles Free Editors’ Choice Articles Impact Factor Articles The Journals of Gerontology, Series A Supplements Special Issues Rights & permissions We are mobile – find out more Journal Career Network Published on behalf of The Gerontological Society of America Impact Factor: 5.416 5-Yr impact factor: 5.406 Editorial Boards The Journals of Gerontology, Series A: Biological Sciences Rafael de Cabo, PhD, Editor View full editorial board The Journals of Gerontology, Series A: Medical Sciences Stephen B. Kritchevsky, PhD View full editorial board For the Media GSA Press Room For Authors Instructions to authors Services for authors Submit Now: Biological Sciences Submit Now: Medical Sciences Self-Archiving Policy Online Submission Open access options for authors - visit Oxford Open WhsSvhnOkaAwYG81FJCYgwG7z1LnIP2F true Looking for your next opportunity? Looking for jobs... jQuery_1_11 = jQuery.noConflict(true); Corporate Services What we offer Advertising sales Reprints Supplements Classified Advertising Sales Alerting Services Email table of contents CiteTrack XML RSS feed

Erickson, Richard R.; Dunning, Lisa M.; Holtzman, Jordan L.

doi: 10.1093/gerona/61.5.435pmid: 16720739

The endoplasmic reticulum (ER) chaperones are highly conserved proteins that catalyze the posttranslational processing of all secretory and membrane proteins. Our studies suggest that chaperone declines are one of the two central defects in Alzheimer's disease. We propose that similar declines in other organ systems underlie the physiological deficits of aging. Rats were maintained in a colony from age 21 days to death. Animals were killed at regular intervals, and hepatic, ER chaperone contents were determined by immunoblotting. ERp55, ERp57, ERp72, BiP, and calnexin constitutive levels declined 30%–50% with age. Calreticulin was unaffected. BiP (also known as GRP78), ERp55, and ERp57 showed marked swings with peaks occurring in midwinter and midsummer. This cyclics declined 73% with age. Considering the role of the ER chaperones in membrane and secretory protein posttranslational processing, these data support the concept that their loss could lead to many of the physiological declines associated with aging.

Erickson, Richard R.; Dunning, Lisa M.; Holtzman, Jordan L.

doi: N/Apmid: N/A

The endoplasmic reticulum (ER) chaperones are highly conserved proteins that catalyze the posttranslational processing of all secretory and membrane proteins. Our studies suggest that chaperone declines are one of the two central defects in Alzheimer's disease. We propose that similar declines in other organ systems underlie the physiological deficits of aging. Rats were maintained in a colony from age 21 days to death. Animals were killed at regular intervals, and hepatic, ER chaperone contents were determined by immunoblotting. ERp55, ERp57, ERp72, BiP, and calnexin constitutive levels declined 30%–50% with age. Calreticulin was unaffected. BiP (also known as GRP78), ERp55, and ERp57 showed marked swings with peaks occurring in midwinter and midsummer. This cyclics declined 73% with age. Considering the role of the ER chaperones in membrane and secretory protein posttranslational processing, these data support the concept that their loss could lead to many of the physiological declines associated with aging.

Henderson, Samuel T.; Bonafè, Massimiliano; Johnson, Thomas E.

doi: 10.1093/gerona/61.5.444pmid: 16720740

Inhibition of either the insulin-like or target of rapamycin (TOR) pathways in the nematode Caenorhabditis elegans extends life span. Here, we demonstrate that starvation and inhibition of the C. elegans insulin receptor homolog (daf-2) elicits a daf-16-dependent up-regulation of a mitochondrial superoxide dismutase (sod-3). We also find that although heat and oxidative stress result in nuclear localization of the DAF-16 protein, these stressors do not activate a SOD-3 reporter, suggesting that nuclear localization alone may not be sufficient for transcriptional activation of DAF-16. We show that inhibition of either TOR activity or key components of the cognate translational machinery (eIF-4G and EIF-2B homologs) increases life span by both daf-16-dependent and -independent mechanisms. Finally, we demonstrate that at least one nematode hexokinase is localized to the mitochondria. We propose that the increased life spans conferred by alterations in both the TOR and insulin-like pathways function by inappropriately activating food-deprivation pathways.