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M A Lane

Publications and source records attributed to M A Lane.

At least 19 recordsLinked to original sources
PubMed2002

Effects of dietary caloric restriction and aging on thyroid hormones of rhesus monkeys.

Plasma levels of thyroid hormones - triiodothyronine (T 3 ), thyroxin (T 4 ), and thyroid-stimulating hormone (TSH) were measured in male and female rhesus monkeys (Macaca mulatta) fed either ad libitum or a 30 % calorie-restricted (CR) diet (males for 11 years; females for 6 years). The same hormones were measured in another group of young male rhesus monkeys during adaptation to the 30 % CR regimen. Both long- and shorter-term CR diet lowered total T 3 in plasma of the monkeys. The effect appeared to be greater in younger monkeys than in older counterparts. No effects of CR diet were detected for either free or total T 4, although unlike T 3, levels of this hormone decreased with age. TSH levels also decreased with age, and were increased by long-term CR diet in older monkeys only. No consistent effects of shorter-term CR diet were observed for TSH. In the light of the effects of the thyroid axis on overall metabolism, these results suggest a possible mechanism by which CR diets may elicit their well-known beneficial 'anti-aging' effects in mammals.

Aging↗
PubMed2002

Developmental changes in ketogenic enzyme gene expression during sheep rumen development.

Ketogenesis is the conversion of acetyl-CoA to the ketone bodies acetoacetate and beta-hydroxybutyrate (BHBA). In hepatic ketogenesis, which occurs during fasting in both nonruminant and ruminant animals, the source of acetyl-CoA is the mitochondrial oxidation of predominantly long-chain fatty acids. In the mature, fed ruminant animal, the ruminal epithelium is also capable of producing ketone bodies. In this case, the source of acetyl-CoA is the mitochondrial oxidation of butyrate produced by the microbial fermentation of feed. The purposes of this study were to determine ontogenic and dietary effects on ketogenic enzyme gene expression in developing lamb ruminal epithelium. Twenty-seven conventionally reared lambs and twenty-seven milk-fed lambs were slaughtered between 1 and 84 d of age. Six additional milk-fed lambs were weaned (the fed group) or maintained on milk replacer with a volatile fatty acid gavage (the VFA group) until 84 d of age. At slaughter, total RNA was extracted from samples of ruminal epithelium. The expression of the genes encoding acetoacetyl-CoA thiolase, the first enzyme in the ketogenic pathway, and 3-hydroxy-3-methylglutaryl-CoA synthase, the rate-limiting enzyme in the ketogenic pathway in nonruminant liver, were examined. Acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase mRNA concentrations increased with age independent of diet. 3-Hydroxy-3-methylglutaryl-CoA synthase mRNA levels in ruminal epithelium obtained from milk-fed lambs were low before 42 d of age, but a marked increase occurred by 42 d of age. At 84 d of age, there were no differences in acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase expression due to diet. The pattern of the expression of these genes, in particular, 3-hydroxy-3-methylglutaryl-CoA synthase, parallels the rate of production of BHBA by rumen epithelial cells isolated from the same lambs, which increased to conventionally reared adult levels at 42 d of age and did not differ with diet. In conclusion, development of the ketogenic capacity of the ruminal epithelium occurs as the animal ages, regardless of dietary treatment. Thus, the expression of the genes encoding the ketogenic enzymes are not affected by the presence of VFA in the ruminal lumen.

3-Hydroxybutyric Acid↗
PubMed2001

Indium-cadmium-oxide films having exceptional electrical conductivity and optical transparency: clues for optimizing transparent conductors.

Materials with high electrical conductivity and optical transparency are needed for future flat panel display, solar energy, and other opto-electronic technologies. In(x)Cd(1-x)O films having a simple cubic microstructure have been grown on amorphous glass substrates by a straightforward chemical vapor deposition process. The x = 0.05 film conductivity of 17,000 S/cm, carrier mobility of 70 cm2/Vs, and visible region optical transparency window considerably exceed the corresponding parameters for commercial indium-tin oxide. Ab initio electronic structure calculations reveal small conduction electron effective masses, a dramatic shift of the CdO band gap with doping, and a conduction band hybridization gap caused by extensive Cd 5s + In 5s mixing.

Journal Article↗
PubMed2001

Age-related changes in cytokine production by leukocytes in rhesus monkeys.

Using a variety of experimental rodent and human models, age-related alterations in cytokine production by immune cells have been described extensively. While the precise mechanism(s) responsible for such age-related changes in cytokine responses remain unclear, it seems likely that these changes may have a significant effect on immune cell function. In an attempt to clarify such changes in aging primates, we examined cytokine production by white cells derived from a controlled colony of rhesus monkeys (Macaca mulatta). Non-fractionated whole blood and peripheral blood mononuclear cells (PBMCs) were obtained from male monkeys of different ages (6-28 years), and were subsequently evaluated for their ability to express mRNA and protein for the cytokines, IL-10, IL-6, IFNgamma, IL-1beta, and TNFalpha, following in vitro stimulation with polyclonal mitogens. Our results suggest that white blood cells derived from aged rhesus monkeys exhibit a significant increase in their ability to produce the Th2-associated cytokine, IL-10, upon stimulation with lipopolysaccharide (LPS) when compared to white cells derived from younger counterparts. Similarly, a significant age-related decrease in the expression of the Th1-associated cytokine, IFNgamma, was also observed using phytohemagglutinin (PHA)-stimulated PBMCs. No significant age-related differences in the production of IL-1beta or TNFalpha were observed in response to any stimulation, but there was limited evidence of an age-related increase in IL-6 production. Overall, our results suggest that a possible systemic change from a Th0/Th1 to a Th2-like cytokine profile occurs in circulating leukocytes derived from aging primates. We believe that such age-related alterations in cytokine production may play a role in the reduced immune responses observed in elderly human populations.

Aging↗
PubMed2001

Strategy for identifying biomarkers of aging in long-lived species.

If effective anti-aging interventions are to be identified for human application, then the development of reliable and valid biomarkers of aging are essential for this progress. Despite the apparent demand for such gerotechnology, biomarker research has become a controversial pursuit. Much of the controversy has emerged from a lack of consensus on terminology and standards for evaluating the reliability and validity of candidate biomarkers. The initiation of longitudinal studies of aging in long-lived non-human primates has provided an opportunity for establishing the reliability and validity of biomarkers of aging potentially suitable for human studies. From the primate study initiated in 1987 at the National Institute on Aging (NIA), the following criteria for defining a biomarker of aging have been offered: (1) significant cross-sectional correlation with age; (2) significant longitudinal change in the same direction as the cross-sectional correlation; (3) significant stability of individual differences over time. These criteria relate to both reliability and validity. However, the process of validating a candidate biomarker requires a greater standard of proof. Ideally, the rate of change in a biomarker of aging should be predictive of lifespan. In short-lived species, such as rodents, populations differing in lifespan can be identified, such as different strains of rodents or groups on different diets, such as those subjected to calorie restriction (CR), which live markedly longer. However, in the NIA primate study, the objective is to demonstrate that CR retards the rate of aging and increases lifespan. In the absence of lifespan data associated with CR in primates, validation of biomarkers of aging must rely on other strategies of proof. With this challenge, we have offered the following strategy: If a candidate biomarker is a valid measure of the rate of aging, then the rate of age-related change in the biomarker should be proportional to differences in lifespan among related species. Thus, for example, the rate of change in a candidate biomarker of aging in chimpanzees should be twice that of humans (60 vs 120 years maximum lifespan); in rhesus monkeys three times that of humans (40 vs 120 years maximum lifespan). The realization of this strategy will be aided by developing a primate aging database, a project that was recently launched in cooperation with the NIA, the National Center for Research Resources, and the University of Wisconsin Regional Primate Research Center.

Aging↗
PubMed2001

A nonhuman primate model of age-related bone loss: a longitudinal study in male and premenopausal female rhesus monkeys.

Aging is associated with gradual bone loss in men and premenopausal women, with an accelerated rate of loss after menopause in women. Although many studies have investigated bone loss due to surgically induced estrogen depletion, little is known regarding normal age-related changes in bone mass in animal models. We used dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD), bone mineral content (BMC), and projected area (PA) at four skeletal sites over 4 years in 20 premenopausal female (8-23 years) and 29 male (8-27 years) rhesus monkeys (Macaca mulatta). Forearm BMD declined with age in both male and female monkeys. Lean mass was positively associated with BMD at all sites in males and with the distal radius in females. Serum osteocalcin declined and urinary cross-links increased with age in males but not females. Serum 25-hydroxyvitamin D concentrations decreased with age in females, and a similar trend was observed in males. In conclusion, an age-related decline in forearm BMD was observed in male and female rhesus monkeys. Total body BMC declined over time in older females, with a similar trend in males. Changes in markers of bone turnover with age were also observed in male monkeys. The results of this longitudinal study suggest that the rhesus monkey is a potential model for age-related changes in the human skeleton.

Absorptiometry, Photon↗
PubMed2001

Accuracy and precision of dual-energy X-ray absorptiometry for body composition measurements in rhesus monkeys.

Accuracy of body composition measurements by dual-energy X-ray absorptiometry (DXA) was compared with direct chemical analysis in 10 adult rhesus monkeys. DXA was highly correlated (r-values > 0.95) with direct analyses of body fat mass (FM), lean mass (LM) and lumbar spine bone mineral content (BMC). DXA measurements of total body BMC were not as strongly correlated (r-value = 0.58) with total carcass ash content. DXA measurements of body FM, LM and lumbar spine BMC were not different from data obtained by direct analyses (P-values > 0.30). In contrast, DXA determinations of total BMC (TBMC) averaged 15%, less than total carcass ash measurements (P = 0.002). In conclusion, this study confirms the accurate measurement of fat and lean tissue mass by DXA in rhesus monkeys. DXA also accurately measured lumbar spine BMC but underestimated total body BMC as compared with carcass ash determinations.

Absorptiometry, Photon↗
PubMed2001

Calorie restriction and skeletal mass in rhesus monkeys (Macaca mulatta): evidence for an effect mediated through changes in body size.

Little is known regarding the effects of prolonged calorie restriction (CR) on skeletal health. We investigated long-term (11 years) and short-term (12 months) effects of moderate CR on bone mass and biochemical indices of bone metabolism in male rhesus monkeys across a range of ages. A lower bone mass in long-term CR monkeys was accounted for by adjusting for age and body weight differences. A further analysis indicated that lean mass, but not fat mass, was a strong predictor of bone mass in both CR and control monkeys. No effect of short-term CR on bone mass was observed in older monkeys (mean age, 19 years), although young monkeys (4 years) subjected to short-term CR exhibited slower gains in total body bone density and content than age-matched controls. Neither biochemical markers of bone turnover nor hormonal regulators of bone metabolism were affected by long-term CR. Although osteocalcin concentrations were significantly lower in young restricted males after 1 month on 30% CR in the short-term study, they were no longer different from control values by 6 months on 30% CR.

Animals↗
PubMed2001

Physiologic effects of lowering caloric intake in nonhuman primates and nonobese humans.

Caloric restriction (CR) reduces the rate of aging and increases life span in all small animal species studied to date, but the effects of CR in humans remain uncertain. This review summarizes current knowledge of the effects of CR in nonhuman primates and humans. The results suggest that CR has a range of beneficial effects in nonhuman primates studied under laboratory conditions, and short-term markers of CR seen in animal models appear to occur in humans subject to CR also. However, the overall benefit of CR in human populations remains to be established, and studies in human populations are needed.

Aging↗
PubMed2001

Energy restriction does not alter bone mineral metabolism or reproductive cycling and hormones in female rhesus monkeys.

Energy restriction (ER) extends the life span and slows aging and age-related diseases in short-lived mammalian species. Although a wide variety of physiological systems have been studied using this paradigm, little is known regarding the effects of ER on skeletal health and reproductive aging. Studies in rhesus monkeys have reported that ER delays sexual and skeletal maturation in young male monkeys and reduces bone mass in adult males. No studies have examined the chronic effects on bone health and reproductive aging in female rhesus monkeys. The present cross-sectional study examined the effects of chronic (6 y) ER on skeletal and reproductive indices in 40 premenopausal and perimenopausal (7-27 y old) female rhesus macaques (Macaca mulatta). Although ER monkeys weighed less and had lower fat mass, ER did not alter bone mineral density, bone mineral content, osteocalcin, 25-hydroxyvitamin D, 1,25-hydroxyvitamin D or parathyroid hormone concentrations, menstrual cycling or reproductive hormone concentrations. Body weight and lean mass were significantly related to bone mineral density and bone mineral content at all skeletal sites (total body, lumbar spine, mid and distal radius; P: < or = 0.04). The number of total menstrual cycles over 2 y, as well as the percentage of normal-length cycles (24-31 d), was lower in older than in younger monkeys (P: < or = 0.05). Older monkeys also had lower estradiol (P: = 0.02) and higher follicle-stimulating hormone (P: = 0.02) concentrations than did younger monkeys. We conclude that ER does not negatively affect these indices of skeletal or reproductive health and does not alter age-associated changes in the same variables.

Aging↗
PubMed2001

Changes in blood chemistry and hematology variables during aging in captive rhesus macaques (Macaca mulatta).

Identifying changes with age in physiological variables of captive nonhuman primates will aid in the proper treatment and clinical diagnosis of these animals, as well as enhance our understanding of nonhuman primate models for human aging. Information for 33 physiological variables was obtained from the Primate Aging Database, a multi-centered database being developed for clinical and research use. Using multiple regression analyses, we investigated the relationship of age to hematological variables, blood chemistry and body weight in 345 captive rhesus monkeys (age range 7-30 years) from three different primate research facilities. The analyses revealed that 15 of these variables show a significant relationship with chronological age and are altered in older as compared with adult animals. Here we present the first phase of a project that will: a) identify changes with age in physiological variables among adult captive rhesus macaques; and b) characterize normative values for the aging rhesus population.

Aging↗
PubMed2001

Caloric restriction in primates.

Caloric restriction (CR) remains the only nongenetic intervention that reproducibly extends mean and maximal life span in short-lived mammalian species. This nutritional intervention also delays the onset, or slows the progression, of many age-related disease processes. The diverse effects of CR have been demonstrated many hundreds of times in laboratory rodents and other short-lived species, such as rotifers, water fleas, fish, spiders, and hamsters. Until recently, the effects of CR in longer-lived species, more closely related to humans, remained unknown. Long-term studies of aging in nonhuman primates undergoing CR have been underway at the National Institute on Aging (NIA) and the University of Wisconsin-Madison (UW) for over a decade. A number of reports from the NIA and UW colonies have shown that monkeys on CR exhibit nearly identical physiological responses as reported in laboratory rodents. Studies of various markers related to age-related diseases suggest that CR will prevent or delay the onset of cardiovascular disease, diabetes, and perhaps cancer, and preliminary data indicate that mortality due to these and other age-associated diseases may also be reduced in monkeys on CR, compared to controls. Conclusive evidence showing that CR extends life span in primates is not presently available; however, the emerging data from the ongoing primate studies strengthens the possibility that the diverse beneficial effects of CR on aging in rodents will also apply to nonhuman primates and perhaps ultimately to humans.

Aging↗
PubMed2001

Caloric restriction in primates and relevance to humans.

Dietary caloric restriction (CR) is the only intervention conclusively and reproducibly shown to slow aging and maintain health and vitality in mammals. Although this paradigm has been known for over 60 years, its precise biological mechanisms and applicability to humans remain unknown. We began addressing the latter question in 1987 with the first controlled study of CR in primates (rhesus and squirrel monkeys, which are evolutionarily much closer to humans than the rodents most frequently employed in CR studies). To date, our results strongly suggest that the same beneficial "antiaging" and/or "antidisease" effects observed in CR rodents also occur in primates. These include lower plasma insulin levels and greater sensitivity; lower body temperatures; reduced cholesterol, triglycerides, blood pressure, and arterial stiffness; elevated HDL; and slower age-related decline in circulating levels of DHEAS. Collectively, these biomarkers suggest that CR primates will be less likely to incur diabetes, cardiovascular problems, and other age-related diseases and may in fact be aging more slowly than fully fed counterparts. Despite these very encouraging results, it is unlikely that most humans would be willing to maintain a 30% reduced diet for the bulk of their adult life span, even if it meant more healthy years. For this reason, we have begun to explore CR mimetics, agents that might elicit the same beneficial effects as CR, without the necessity of dieting. Our initial studies have focused on 2-deoxyglucose (2DG), a sugar analogue with a limited metabolism that actually reduces glucose/energy flux without decreasing food intake in rats. In a six-month pilot study, 2DG lowered plasma insulin and body temperature in a manner analagous to that of CR. Thus, metabolic effects that mediate the CR mechanism can be attained pharmacologically. Doses were titrated to eliminate toxicity; a long-term longevity study is now under way. In addition, data from other laboratories suggest that at least some of the same physiological/metabolic end points that are associated with the beneficial effects of underfeeding may be obtained from other potential CR mimetic agents, some naturally occurring in food products. Much work remains to be done, but taken together, our successful results with CR in primates and 2DG administration to rats suggest that it may indeed be possible to obtain the health- and longevity-promoting effects of the former intervention without actually decreasing food intake.

Aging↗
PubMed2001

Aging and caloric restriction in nonhuman primates: behavioral and in vivo brain imaging studies.

In a long-term longitudinal study of aging in rhesus monkeys, a primary objective has been to determine the effects of aging and caloric restriction (CR) on behavioral and neural parameters. Through the use of automated devices, locomotor activity can be monitored in the home cages of the monkeys. Studies completed thus far indicate a clear age-related decline in activity consistent with such observations in many other species, including humans. However, no consistent effects of CR on activity have been observed. Selected groups of monkeys have also been involved in brain imaging studies, using magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI studies completed thus far reveal a clear age-related decline in the volumes of the basal ganglia, the putamen, and the caudate nucleus, with no change in total brain volume. PET analysis has revealed an age-related decline in the binding potential of dopamine D2 receptors in the same brain regions. These results are consistent with findings in humans. Although additional longitudinal analysis is needed to confirm the present results, it would appear that locomotor activity, volume of the basal ganglia, as well as dopamine D2 receptor binding potential provide reliable, noninvasive biomarkers of aging in rhesus monkeys.

Aging↗
PubMed2001

Cryptosporidium parvum infection requires host cell actin polymerization.

The intracellular protozoan parasite Cryptosporidium parvum accumulates host cell actin at the interface between the parasite and the host cell cytoplasm. Here we show that the actin polymerizing proteins Arp2/3, vasodilator-stimulated phosphoprotein (VASP), and neural Wiskott Aldrich syndrome protein (N-WASP) are present at this interface and that host cell actin polymerization is necessary for parasite infection.

Actin-Related Protein 2↗
PubMed2001

Dietary caloric restriction prevents the age-related decline in plasma melatonin levels of rhesus monkeys.

Rhesus monkeys exhibit an age-associated decrease in peak plasma melatonin levels analogous to that reported for humans. This decrease is essentially abolished in monkeys subjected to a 30% reduction in caloric intake over a 12-yr period. The caloric restriction (CR) effect does not seem to be a reversal, but rather a long-term prevention, of the age-related decline in hormone concentrations. The age effect does not seem to be due to a phase shift in the peak of melatonin secretions, as has been observed in some populations of aged humans. It is also extremely unlikely that the CR effect simply reflects a phase shift, since old monkeys on the diet have nocturnal melatonin levels equal to or greater than adult fully fed controls. Thus, if peak times (approximately 0200 h) were actually shifted, maximal levels in old CR monkeys would be even higher. These findings, coupled with previous observations in humans, suggest that peak plasma melatonin levels may represent a possible candidate "biomarker of aging" in primates. Moreover, this index of age-associated physiological decrement seems to be inhibited by dietary CR.

Aging↗
PubMed2000

Interoperability of biodiversity databases: biodiversity information on every desktop.

Data about biodiversity are either scattered in many databases or reside on paper or other media not amenable to interactive searching. The Global Biodiversity Information Facility (GBIF) is a framework for facilitating the digitization of biodiversity data and for making interoperable an as-yet-unknown number of biodiversity databases that are distributed around the globe. In concert with other existing efforts, GBIF will catalyze the completion of a Catalog of the Names of Known Organisms and will develop search engines to mine the vast quantities of biodiversity data. It will be an outstanding tool for scientists, natural resource managers, and policy-makers.

Animals↗