Expression of a Single-Copy hsp-16.2 Reporter Predicts Life span.
J Gerontol A Biol Sci Med Sci. 2012 Jan 6;
Authors: Mendenhall AR, Tedesco PM, Taylor LD, Lowe A, Cypser JR, Johnson TE
Abstract
The level of green fluorescent protein expression from an hsp-16.2-based transcriptional reporter predicts life span and thermotolerance in Caenorhabditis elegans. The initial report used a high-copy number reporter integrated into chromosome IV. There was concern that the life-span prediction power of this reporter was not attributable solely to hsp-16.2 output. Specifically, prediction power could stem from disruption of some critical piece of chromatin on chromosome IV by the gpIs1 insertion, a linked mutation from the process used to create the reporter, or from an artifact of transgene regulation (multicopy transgenes are subject to regulation by C elegans chromatin surveillance machinery). Here we determine if the ability to predict life span and thermotolerance is specific to the gpIs1 insertion or a general property of hsp-16.2-based reporters. New single-copy hsp-16.2-based reporters predict life span and thermotolerance. We conclude that prediction power of hsp-16.2-based transcriptional reporters is not an artifact of any specific transgene configuration or chromatin surveillance mechanism.
PMID: 22227523 [PubMed - as supplied by publisher]
Occurrence of Hypotension in Older Participants. Which 24-hour ABPM Parameter Better Correlate With?
J Gerontol A Biol Sci Med Sci. 2012 Jan 6;
Authors: Scuteri A, Modestino A, Frattari A, Di Daniele N, Tesauro M
Abstract
Objectives.The aim of the present study was to investigate the prevalence of hypotension in older participants and to identify which 24-hour ambulatory blood pressure monitoring parameter better correlated with the occurrence of hypotension. METHODS: We studied 588 elderly participants (mean age 78.7 ± 7.1 years; 70% women) who underwent a 24-hour ambulatory blood pressure (BP) monitoring, without moderate-to-severe cognitive impairment, myocardial infarction, or stroke within the previous 6 months; renal (serum creatinine > 2.5 mg/dL), respiratory, or liver insufficiency; and atrial fibrillation. RESULTS: In older participants, the occurrence of systolic hypotension is very common (≈55% presenting at least one episode of systolic blood pressure (SBP) < 100 mmHg and about 20% presenting ≥10% of the SBP registrations < 100 mmHg). More than 30% of participants with 24-hour SBP, daytime, and nighttime above the reference threshold had hypotension. Hypotension did not correlated with BP variability indices (standard deviation of BPs). None of the parameters commonly present in 24-hour ambulatory BP monitoring clinical reports is able to accurately identify those older participants with episode of hypotension. CONCLUSION: Episodes of SBP hypotension are extremely common in older participants and do not appear to relate to BP variability indices. Indeed, no parameter of 24-hour ambulatory BP monitoring was capable to accurately identify the occurrence of hypotension. We expect that ongoing studies will contribute to identification of specific factors predicting hypotensive episodes in the older participants.
PMID: 22227524 [PubMed - as supplied by publisher]
Age-Associated Proinflammatory Secretory Phenotype in Vascular Smooth Muscle Cells From the Non-human Primate Macaca mulatta: Reversal by Resveratrol Treatment.
J Gerontol A Biol Sci Med Sci. 2012 Jan 4;
Authors: Csiszar A, Sosnowska D, Wang M, Lakatta EG, Sonntag WE, Ungvari Z
Abstract
There is increasing evidence that age-associated chronic low-grade inflammation promotes the development of both large-vessel disease (myocardial infarction, stroke, peripheral arterial disease) and small-vessel pathologies (including vascular cognitive impairment) in older persons. However, the source of age-related chronic vascular inflammation remains unclear. To test the hypothesis that cell-autonomous mechanisms contribute to the proinflammatory changes in vascular phenotype that accompanies advancing age, we analyzed the cytokine secretion profile of primary vascular smooth muscle cells (VSMCs) derived from young (∼13 years old) and aged (∼21 years old) Macaca mulatta. Aged VSMCs cultured in the absence of systemic factors exhibited significantly increased secretion of interleukin-1β, MCP-1, and tumor necrosis factorα compared with young control cells. Secretion of interleukin-6 also tended to increase in aged VSMCs. This age-associated proinflammatory shift in the cellular secretory phenotype was associated with an increased mitochondrial O(2)(-) production and nuclear factor κ-light-chain-enhancer of activated B cells activation. Treatment of aged VSMCs with a physiologically relevant concentration of resveratrol (1 μM) exerted significant anti-inflammatory effects, reversing aging-induced alterations in the cellular cytokine secretion profile and inhibiting nuclear factor κ-light-chain-enhancer of activated B cells. Resveratrol also attenuated mitochondrial O(2)(-) production and upregulated the transcriptional activity of Nrf2 in aged VSMCs. Thus, in non-human primates, cell-autonomous activation of nuclear factor κ-light-chain-enhancer of activated B cells and expression of an inflammatory secretome likely contribute to vascular inflammation in aging. Resveratrol treatment prevents the proinflammatory properties of the aged VSMC secretome, an effect that likely contributes to the demonstrated vasoprotective action of resveratrol in animal models of aging.
PMID: 22219513 [PubMed - as supplied by publisher]
We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100-104 years), semisupercentenarians (age 105-109 years), and supercentenarians (age 110-119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0-13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed.
PMID: 22219514 [PubMed - as supplied by publisher]
The redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2) plays a key role in preserving a healthy endothelial phenotype and maintaining the functional integrity of the vasculature. Previous studies demonstrated that aging is associated with Nrf2 dysfunction in endothelial cells, which alters redox signaling and likely promotes the development of large vessel disease. Much less is known about the consequences of Nrf2 dysfunction at the level of the microcirculation. To test the hypothesis that Nrf2 regulates angiogenic capacity of endothelial cells, we determined whether disruption of Nrf2 signaling (by siRNA knockdown of Nrf2 and overexpression of Keap1, the cytosolic repressor of Nrf2) impairs angiogenic processes in cultured human coronary arterial endothelial cells stimulated with vascular endothelial growth factor and insulin-like growth factor-1. In the absence of functional Nrf2, coronary arterial endothelial cells exhibited impaired proliferation and adhesion to vitronectin and collagen. Disruption of Nrf2 signaling also reduced cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing technology) and impaired the ability of coronary arterial endothelial cells to form capillary-like structures. Collectively, we find that Nrf2 is essential for normal endothelial angiogenic processes, suggesting that Nrf2 dysfunction may be a potential mechanism underlying impaired angiogenesis and microvascular rarefaction in aging.
PMID: 22219515 [PubMed - as supplied by publisher]
Testing the Oxidative Stress Hypothesis of Aging in Primate Fibroblasts: Is There a Correlation Between Species Longevity and Cellular ROS Production?
J Gerontol A Biol Sci Med Sci. 2012 Jan 4;
Authors: Csiszar A, Podlutsky A, Podlutskaya N, Sonntag WE, Merlin SZ, Philipp EE, Doyle K, Davila A, Recchia FA, Ballabh P, Pinto JT, Ungvari Z
Abstract
The present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts from 13 primate species ranging in body size from 0.25 to 120 kg and in longevity from 20 to 90 years. We assessed both basal and stress-induced reactive oxygen species production in fibroblasts from five great apes (human, chimpanzee, bonobo, gorilla, and orangutan), four Old World monkeys (baboon, rhesus and crested black macaques, and patas monkey), three New World monkeys (common marmoset, red-bellied tamarin, and woolly monkey), and one lemur (ring-tailed lemur). Measurements of cellular MitoSox fluorescence, an indicator of mitochondrial superoxide $$\left({\hbox{ O }}_{2}^{\cdot -}\right)$$ generation, showed an inverse correlation between longevity and steady state or metabolic stress-induced mitochondrial $${\hbox{ O }}_{2}^{\cdot -}$$ production, but this correlation was lost when the effects of body mass were removed, and the data were analyzed using phylogenetically independent contrasts. Fibroblasts from longer-lived primate species also exhibited superior resistance to H(2)O(2)-induced apoptotic cell death than cells from shorter-living primates. After correction for body mass and lack of phylogenetic independence, this correlation, although still discernible, fell short of significance by regression analysis. Thus, increased longevity in this sample of primates is not causally associated with low cellular reactive oxygen species generation, but further studies are warranted to test the association between increased cellular resistance to oxidative stressor and primate longevity.
PMID: 22219516 [PubMed - as supplied by publisher]
Pilot Study of Resveratrol in Older Adults With Impaired Glucose Tolerance.
J Gerontol A Biol Sci Med Sci. 2012 Jan 4;
Authors: Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, Hawkins M, Cohen HW, Barzilai N
Abstract
BACKGROUND: Resveratrol, a plant-derived polyphenol, has shown promising effects on insulin sensitivity and glucose tolerance in animal models and is also reported to have cardioprotective properties, but human studies are limited. In a pilot study, we tested the hypothesis that resveratrol improves glucose metabolism and vascular function in older adults with impaired glucose tolerance (IGT). METHODS: Ten subjects aged 72 ± 3 years (M ± SD) with IGT were enrolled in a 4-week open-label study of resveratrol (daily dose 1, 1.5, or 2 g). Following a standard mixed meal (110 g carbohydrate, 20 g protein, 20 g fat), we measured 3-hour glucose and insulin area under the curve (AUC), insulin sensitivity (Matsuda index), and secretion (corrected insulin response at 30 minutes). Endothelial function was assessed by reactive hyperemia peripheral arterial tonometry (reactive hyperemia index) before and 90 minutes postmeal. Results did not differ by dose, so data were combined for analysis. RESULTS: At baseline, body mass index was 29 ± 5 kg/m(2), fasting plasma glucose 110 ± 13 mg/dL, and 2-hour glucose 183 ± 33 mg/dL. After 4 weeks of resveratrol, fasting plasma glucose was unchanged, but peak postmeal (185 ± 10 vs 166 ± 9 mg/dL, p = .003) and 3-hour glucose AUC (469 ± 23 vs 428 ± 19, p = .001) declined. Matsuda index improved (3.1 ± 0.5 vs 3.8 ± 0.5, p = .03), and corrected insulin response at 30 minutes was unchanged (0.6 ± 0.1 vs 0.5 ± 0.5, p = .49). There was a trend toward improved postmeal reactive hyperemia index (baseline vs resveratrol postmeal delta -0.4 ± 0.2 vs 0.2 ± 0.3, p = .06). Weight, blood pressure, and lipids were unchanged. CONCLUSIONS: At doses between 1 and 2 g/day, resveratrol improves insulin sensitivity and postmeal plasma glucose in subjects with IGT. These preliminary findings support the conduct of larger studies to further investigate the effects of resveratrol on metabolism and vascular function.
PMID: 22219517 [PubMed - as supplied by publisher]
The Pattern of Recovery of Ambulation After Hip Fracture Differs With Age in Elderly Patients.
J Gerontol A Biol Sci Med Sci. 2012 Jan 4;
Authors: Ortiz-Alonso FJ, Vidán-Astiz M, Alonso-Armesto M, Toledano-Iglesias M, Alvarez-Nebreda L, Brañas-Baztan F, Serra-Rexach JA
Abstract
BACKGROUND: The main objective of this study was to analyze the independent effect of increasing age on the recovery of different areas of functioning 1 year after hip fracture. METHODS: Consecutive 1-year survivors aged ≥65 years (n = 362) admitted to a single hospital for acute hip fracture surgery were followed prospectively for 1 year. Age was stratified as <75, 75-84, and ≥85 years. Basic activities of daily living and ambulation were measured by personal interview during hospitalization and phone contact at 3, 6, and 12 months. Longitudinal data of recovery in these areas were analyzed using generalized estimating equations. RESULTS: Older age was strongly associated with poor recovery in all areas of function, except eating. The pattern of recovery of ambulation differed with age, peaking at 6 months in the younger group and continuing for at least 12 months in the eldest group. The pattern of recovery of overall and individual activities of daily living was similar in the three age groups. Recovery of areas associated with upper extremity function peaked at 3 months, whereas areas associated with lower extremity function peaked at 6 months. CONCLUSIONS: The patterns of functional disability after hip fracture differ with areas of function and age with the oldest patients having a particular risk of decline and a prolonged time to recovery of ambulation.
PMID: 22219518 [PubMed - as supplied by publisher]
The case for prioritizing the study of the biology of aging can be persuasively made by making explicit its connection to the exercise of the intellectual virtues needed to realize well-ordered science. These intellectual virtues include a range of attitudes and dispositions integral to all areas of science (e.g. sensitivity to details, adaptability of intellect, the detective’s virtues), but the so-called “teaching virtues” are especially important for biogerontology. Without the foresight to anticipate how their audience will likely respond, biogerontologists risk marginalizing the field’s importance to well-ordered science as the general public are likely to dismiss, or underestimate, the health and economic benefits of an intervention that retards the rate of biological aging.
PMID: 22219519 [PubMed - as supplied by publisher]
Polypharmacy in Nursing Home in Europe: Results From the SHELTER Study.
J Gerontol A Biol Sci Med Sci. 2012 Jan 4;
Authors: Onder G, Liperoti R, Fialova D, Topinkova E, Tosato M, Danese P, Gallo PF, Carpenter I, Finne-Soveri H, Gindin J, Bernabei R, Landi F,
Abstract
BACKGROUND: This study assesses prevalence and patients characteristics related to polypharmacy in a sample of nursing home residents. METHODS: We conducted a cross-sectional analysis on 4,023 nursing home residents participating to the Services and Health for Elderly in Long TERm care (SHELTER) project, a study collecting information on residents admitted to 57 nursing home in 8 countries. Data were collected using the interRAI instrument for long-term care facilities. Polypharmacy status was categorized in 3 groups: non-polypharmacy (0-4 drugs), polypharmacy (5-9 drugs) and excessive polypharmacy (≥10 drugs). RESULTS: Polypharmacy was observed in 2,000 (49.7%) residents and excessive polypharmacy in 979 (24.3%) residents. As compared with non-polypharmacy, excessive polypharmacy was directly associated not only with presence of chronic diseases but also with depression (odds ratio [OR] 1.81; 95% confidence interval [CI] 1.38-2.37), pain (OR 2.31; 95% CI 1.80-2.97), dyspnoea (OR 2.29; 95% CI 1.61-3.27), and gastrointestinal symptoms (OR 1.73; 95% CI 1.35-2.21). An inverse association with excessive polypharmacy was shown for age (OR for 10 years increment 0.85; 95% CI 0.74-0.96), activities of daily living disability (OR for assistance required vs independent 0.90; 95% CI 0.64-1.26; OR for dependent vs independent 0.59; 95% CI 0.40-0.86), and cognitive impairment (OR for mild or moderate vs intact 0.64; 95% CI 0.47-0.88; OR for severe vs intact 0.39; 95% CI 0.26-0.57). CONCLUSIONS: Polypharmacy and excessive polypharmacy are common among nursing home residents in Europe. Determinants of polypharmacy status include not only comorbidity but also specific symptoms, age, functional, and cognitive status.
PMID: 22219520 [PubMed - as supplied by publisher]
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