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M A Lane

Publications and source records attributed to M A Lane.

At least 55 records · Page 3Linked to original sources
PubMed1999

Loss of D2 receptor binding with age in rhesus monkeys: importance of correction for differences in striatal size.

The relation between striatal dopamine D2 receptor binding and aging was investigated in rhesus monkeys with PET. Monkeys (n = 18, 39 to 360 months of age) were scanned with 11C-raclopride; binding potential in the striatum was estimated graphically. Because our magnetic resonance imaging analysis revealed a concomitant relation between size of striatum and age, the dynamic positron emission tomography (PET) data were corrected for possible partial volume (PV) artifacts before parameter estimation. The age-related decline in binding potential was 1% per year and was smaller than the apparent effect if the age-related change in size was ignored. This is the first in vivo demonstration of a decline in dopamine receptor binding in nonhuman primates. The rate of decline in binding potential is consistent with in vitro findings in monkeys but smaller than what has been measured previously in humans using PET. Previous PET studies in humans, however, have not corrected for PV error, although a decline in striatal size with age has been demonstrated. The results of this study suggest that PV correction must be applied to PET data to accurately detect small changes in receptor binding that may occur in parallel with structural changes in the brain.

Aging↗
PubMed1999

Calorie restriction in primates: will it work and how will we know?

Dietary caloric restriction is the most robust and reproducible means of slowing aging and extending lifespan and healthspan in short-lived mammals and lower organisms. Numerous aspects of this paradigm have been investigated in laboratories around the world since its inception more than 60 years ago. However, two questions about calorie restriction remain unanswered to this day: (1) By what mechanism does it work? and (2) Will it work in humans? This review will focus on the latter with particular emphasis on evaluation criteria, current studies in primate models, available data, and plans for actual human caloric restriction interventions.

Aging↗
PubMed1999

Skeletal effects of aging and menopausal status in female rhesus macaques.

To further define the nonhuman primate as a model of the adult human skeleton, we explored the impact of growth, natural menopause, and osteoarthritis on bone mass, serum markers of bone turnover (osteocalcin and C-terminal telopeptide of type I collagen) and measures of skeletal relevance (PTH, 25-hydroxyvitamin D, total alkaline phosphatase, calcium, phosphorus, creatinine, and albumin). Fifty-eight female (aged 4-30 yr) rhesus macaques were defined as growing (G; n = 12; < or = 10 yr old), adult premenopausal (APre; n = 30; > 10 yr old; eumenorrheic, high serum estradiol and low FSH), or postmenopausal (Post; n = 16; amenorrheic for at least 1 yr, with low serum estradiol and high FSH). Total body and posterior-anterior spinal bone masses were lower in G than APre animals (P < 0.05). Post females had lower total body, distal radius, and spinal bone mass than premenopausal animals (P < 0.05). Osteocalcin was higher in Post than APre animals (P < 0.01). Other measures showed no relationship with menopausal status. In older monkeys, spinal osteoarthritis became common, causing increased dual-energy x-ray absorptiometry-measured bone mass in the lumbar spinal posterior-anterior projection. In conclusion, after natural menopause, rhesus monkeys have lower bone mass and higher skeletal turnover without alteration of the calcium-vitamin D axis. As such, they are an excellent model of human estrogen-depletion bone loss.

Absorptiometry, Photon↗
PubMed1999

Nutritional modulation of aging in nonhuman primates.

Caloric restriction (CR), undernutrition without malnutrition, remains the only experimental paradigm that has been shown consistently to extend lifespan and slow aging in short-lived species. Decades of research, mostly in laboratory rodents, have shown that CR consistently extends lifespan, reduces or delays the onset of many age-related diseases and slows aging in many physiological systems. In recent years gerontologists interested in CR have focused on two unanswered questions. 1) What is the relevance of this nutritional paradigm to human aging? and 2) What biological mechanism(s) underlie the diverse effects of CR leading to a retardation of aging and disease?. To address the question of human relevance, researchers in the Intramural Research Program of the National Institute on Aging began a study of CR in nonhuman primates in the late 1980s. In addition to assessing the effects of CR on aging in primates, a major focus of this work relates to possible metabolic mechanisms of CR. A subsequent study at the University of Wisconsin Madison was initiated in the early 1990s. Certain aspects of experimental design differ between these two important ongoing investigations, but generally these studies compliment each other in many ways and have begun to provide much important data regarding the effects of CR in primates. Emerging data from these studies strongly support that physiological responses to CR in monkeys parallel the extensive findings reported in rodents. Lifespan data will not be available for several years, however, the remarkable consistency with rodent studies, in which lifespan extension is documented extensively, strengthens the possibility that CR will also extend lifespan in primates, perhaps including humans. This review summarizes the major findings from the primate CR studies after over a decade of research in this model.

Aging↗
PubMed1998

A strategy for identifying biomarkers of aging: further evaluation of hematology and blood chemistry data from a calorie restriction study in rhesus monkeys.

We examined a dataset derived from a battery of hematology and blood chemistry tests to identify candidate biomarkers of aging in a sample of 33 male rhesus monkeys (Macaca mulatta) ranging in age from 4-27 years. About half this sample comprised an experimental group subjected to 30% calorie restriction for six to seven years compared to the control group fed the same nutritionally fortified diet to approximate ad lib levels. Variables that met the following criteria were selected: (1) longitudinal change within the cohorts of control monkeys; (2) cross-sectional correlation with age across the adult lifespan in the control group; (3) stability of individual differences within all groups; and (4) no obvious redundancy with other selected variables. Five variables emerged from this step-wise selection, including the percentage lymphocytes, and serum levels of alkaline phosphatase, albumin, creatinine, and calcium. These variables were then submitted to a principal component analysis, which yielded a single component accounting for about 58% of the total variance. Based on this marked degree of covariance, these candidate biomarkers of aging could be combined into a biological age score (BAS) for the control and experimental groups. When chronological age was regressed onto BAS, the slopes of the control and experimental groups could be compared. Although a trend toward a slower aging rate in calorie-restricted monkeys was apparent, this analysis did not detect a statistically significant difference in the rate of aging between these groups estimated by this index. Despite this result, a logical strategy was confirmed for expanding the search for candidate biomarkers of aging to apply to this and to other studies assessing interventions that purport to affect the rate of aging in long-lived species.

Aging↗
PubMed1997

Dietary restriction in rhesus monkeys: lymphopenia and reduced mitogen-induced proliferation in peripheral blood mononuclear cells.

Dietary restriction (DR) markedly extends mean and maximal life span, and retards the rate of biological aging in rodent models; however, it is unknown if these results occur in primate species. The purpose of the current study was to investigate selected immunologic outcomes in Rhesus monkeys subjected to DR for a period of seven years. Similar to observations in mice on DR, lymphopenia occurred in the restricted monkeys. Compared to normally fed controls, the mitogen-induced proliferative responses of peripheral blood mononuclear cells (PBMC) were reduced in monkeys subjected to DR very early in life (up to 1 year), but not in others restricted in young adulthood (3-5 years). These data indicate that lymphopenia is a shared occurrence in rodents and primates on DR. However, the mitogen-induced proliferative data accumulated in rodents and primates cannot now be compared because PBMC have not been studied long enough or in comparable detail in primates fed restricted diets.

Aging↗
PubMed1997

Activity measures in rhesus monkeys on long-term calorie restriction.

Calorie restriction (CR), undernutrition without malnutrition, extends the mean and maximal lifespan of several ecologically diverse species. Rodents on CR demonstrate increased activity measured as spontaneous locomotion, wheel running, open field behavior or movement. Activity measures were recorded from 19 male rhesus monkeys (Macaca mulatta) as either controls (C) which were fed a nutritious diet to approximate ad libitum levels, or as experimentals (E) which were fed 30% less than age- and weight-matched controls. Within each diet group, some monkeys (n = 10) began CR at 2.3 years of age (range 2.2-2.4 yrs, J Group) while another group (n = 9) began CR at approximately 4.6 years of age (range 4-5.25, A group). Beginning about 6 years after initiation of the study, behavioral activity was measured via ultrasonic motion detectors and recorded on videotape. Diurnal and circadian activity was clearly discernible. Peaks in activity were associated with mealtime and colony husbandry. Compared to Group A, Group J monkeys exhibited higher overall activity as measured by sensors, and also significantly more circling. Compared to AC monkeys, group AE monkeys demonstrated higher rates of gross motor behavior, pacing, stereotypies and grooming. The increases in motor activity observed in one group of monkeys were consistent with results obtained from rodent studies of CR and aging. CR did not significantly inhibit or negatively influence the display of behavior of rhesus monkeys in the laboratory environment. We report here, for the first time, increases in activity due to CR in a model other than the rodent.

Animals↗
PubMed1997

Polymerase chain reaction-based detection of B-cell clonality in the fine needle aspiration biopsy of a thyroid mucosa-associated lymphoid tissue (MALT) lymphoma.

Although it is possible to diagnose primary high-grade thyroid lymphoma from a fine needle aspiration (FNA) biopsy, the distinction of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) from lymphocytic thyroiditis is sometimes problematic. Definitive diagnosis of lymphoma on cytologic specimens may be facilitated by the documentation of a clonal lymphoid proliferation within the specimen by flow cytometric immunophenotyping or immunocytochemistry. Recently, molecular techniques have also been developed to detect clonal lymphoid proliferation based on immunoglobulin (Ig) or T-cell receptor gene rearrangement. We have used a polymerase chain reaction (PCR)-based assay for Ig heavy chain gene arrangement to identify a clonal population of lymphocytes within the thyroid FNA specimen from a low-grade thyroid MALT lymphoma. Using this assay, we identified no distinct clonal population in five cytologic specimens of lymphocytic thyroiditis. Therefore, this PCR-based clonality assay represents a potentially useful adjunct to the cytologic diagnosis of thyroid lymphoma.

Aged↗
PubMed1997

Effect of age and caloric restriction on cutaneous wound closure in rats and monkeys.

Cutaneous wounds close more slowly in rats and monkeys as age increases. Caloric restriction of 40% in rats and 30% in monkeys did not significantly affect healing rates, although it did exert a trend toward faster closure. Similarly, voluntary exercise did not significantly alter healing rates in rats. Thus, impaired wound healing appears to be a generalized physiological manifestation of aging, but its possible amelioration by "anti-aging" interventions remains to be established.

Aging↗
PubMed1997

Caloric restriction increases HDL2 levels in rhesus monkeys (Macaca mulatta).

Caloric restriction (CR) prolongs the life of rodents and other small animals, but the benefits of CR for primates and people are as yet unknown, and mechanisms by which CR may slow aging remain unidentified. A study of rhesus monkeys, Macaca mulatta, is underway to determine if CR might prolong life span in primates and to evaluate potential mechanisms for life prolongation. Thirty rhesus monkeys in three age cohorts, restricted to 70% of ad libitum calorie intake for 6-7 yr, were compared with 30 controls. Plasma lipid, lipoprotein, and high-density lipoprotein (HDL) apolipoproteins and subfractions were measured and compared with weight, percent fat, glucose, and insulin level. CR caused decreased triglyceride levels in adult monkeys and increased levels of HDL2b, the HDL subfraction associated with protection from atherosclerosis. Multivariate statistical analyses showed that differences in lipid and lipoprotein levels occurring with CR could be accounted for, at least in part, by decreased body mass and improved glucose regulation. These studies have used a novel dietary modification paradigm in nonhuman primates focused on calorie reduction. Results suggest that CR, as mediated by its beneficial effect on body composition and glucose metabolism, could prolong human life by decreasing the incidence of atherosclerosis.

Aging↗
PubMed1997

Dehydroepiandrosterone sulfate: a biomarker of primate aging slowed by calorie restriction.

The adrenal steroids, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), have attracted attention for their possible antiaging effects. DHEAS levels in humans decline markedly with age, suggesting the potential importance of this parameter as a biomarker of aging. Here we report that, as seen in humans, male and female rhesus monkeys exhibit a steady, age-related decline in serum DHEAS. This decline meets several criteria for a biomarker of aging, including cross-sectional and longitudinal linear decreases with age and significant stability of individual differences over time. In addition, the proportional age-related loss of DHEAS in rhesus monkeys is over twice the rate of decline observed in humans. Most important is the finding that, in rhesus monkeys, calorie restriction, which extends life span and retards aging in laboratory rodents, slows the postmaturational decline in serum DHEAS levels. This represents the first evidence that this nutritional intervention has the potential to alter aspects of postmaturational aging in a long-lived species.

Aging↗
PubMed1997

Effect of volatile fatty acid infusion on development of the rumen epithelium in neonatal sheep.

The purpose of this study was to determine whether the continuous intraruminal infusion of calculated physiological concentrations of volatile fatty acids (VFA) stimulated the metabolic development of the neonatal rumen. Eight 1-wk-old lambs were assigned to one of three treatments: saline infusion (three lambs), VFA infusion (three lambs), or no infusion (two lambs). Rumen catheters were surgically implanted into lambs in the infusion groups. The amount of VFA infused, beginning at 2 wk of age, increased weekly in equal increments of 12.5% of the estimated net energy requirement until, at 6 wk of age, lambs received 50% of their estimated net energy requirement from the infused VFA. All lambs consumed milk replacer for ad libitum intake and had free access to water. The lambs that were infused with VFA tended to have longer rumen papillae. There were no differences in width or number of papillae per square centimeter across treatments. Rumen epithelial cells isolated from lambs that were infused with VFA tended to oxidize less glucose and produce more acetoacetate than did cells from lambs that were infused with saline or from uninfused lambs. beta-Hydroxybutyrate production by isolated rumen epithelial cells and concentrations of blood glucose, acetoacetate, and beta-hydroxybutyrate were not different among the three treatments. Thus, infusion of physiological concentrations of VFA appears to stimulate some aspects of rumen metabolic development.

Acetoacetates↗
PubMed1997

Plan and operation of the NHANES I Epidemiologic Followup Study, 1992.

OBJECTIVES: The NHANES I Epidemiologic Followup Study (NHEFS) is a longitudinal study that uses as its baseline those adult persons 25-74 years of age who were examined in the first National Health and Nutrition Examination Survey (NHANES I). NHEFS was designed to investigate the association between factors measured at baseline and the development of specific health conditions. The three major objectives of NHEFS are to study morbidity and mortality associated with suspected risk factors, changes over time in participants' characteristics, and the natural history of chronic disease and functional impairments. METHODS: Tracing and data collection in the 1992 Followup were undertaken for the 11,195 subjects who were not known to be deceased in the previous surveys. No additional information was collected in the 1992 NHEFS for the 3,212 subjects who were known to be deceased before the 1992 NHEFS data collection period. RESULTS: By the end of the 1992 NHEFS survey period, 90.0 percent of the 11,195 subjects in the 1992 Followup cohort had been successfully traced. Interviews were conducted for 9,281 subjects. An interview was conducted for 8,151 of the 8,687 surviving subjects; 551 interviews were administered to a proxy respondent because the subject was incapacitated. A proxy interview was conducted for 1,130 of the 1,392 decedents identified in the 1992 NHEFS. In addition, 10,535 facility stay records were collected for 4,162 subjects reporting overnight facility stays. Death certificates were obtained for 1,374 of the 1,392 subjects who were identified as deceased since last contact. Approximately 32 percent of the NHEFS cohort is known to be deceased with a death certificate available for 98 percent of the 4,604 NHEFS decedents.

Adult↗
PubMed1996

Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents.

Many studies of caloric restriction (CR) in rodents and lower animals indicate that this nutritional manipulation retards aging processes, as evidenced by increased longevity, reduced pathology, and maintenance of physiological function in a more youthful state. The anti-aging effects of CR are believed to relate, at least in part, to changes in energy metabolism. We are attempting to determine whether similar effects occur in response to CR in nonhuman primates. Core (rectal) body temperature decreased progressively with age from 2 to 30 years in rhesus monkeys fed ad lib (controls) and is reduced by approximately 0.5 degrees C in age-matched monkeys subjected to 6 years of a 30% reduction in caloric intake. A short-term (1 month) 30% restriction of 2.5-year-old monkeys lowered subcutaneous body temperature by 1.0 degrees C. Indirect calorimetry showed that 24-hr energy expenditure was reduced by approximately 24% during short-term CR. The temporal association between reduced body temperature and energy expenditure suggests that reductions in body temperature relate to the induction of an energy conservation mechanism during CR. These reductions in body temperature and energy expenditure are consistent with findings in rodent studies in which aging rate was retarded by CR, now strengthening the possibility that CR may exert beneficial effects in primates analogous to those observed in rodents.

Aging↗
PubMed1996

Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence.

A fundamental question in the basic biology of aging is whether there is a universal aging process. If indeed such a process exists, one would expect that it develops at a higher rate in short- versus long-lived species. We have quantitated pentosidine, a marker of glycoxidative stress in skin collagen from eight mammalian species as a function of age. A curvilinear increase was modeled for all species, and the rate of increase correlated inversely with maximum life-span. Dietary restriction, a potent intervention associated with increased life-span, markedly inhibited glycoxidation rate in the rodent. On the assumption that collagen turnover rate is primarily influenced by the crosslinking due to glycoxidation, these results suggest that there is a progressive age-related deterioration of the process that controls the collagen glycoxidation rate. Thus, the ability to withstand damage due to glycoxidation and the Maillard reaction may be under genetic control.

Aging↗
PubMed1995

Effects of aging and dietary restriction on activity of monkey serum in promoting fibroblast migration.

In order to determine whether serum modified cellular aging in vivo, we previously studied the effects of serum from various mammals of different ages on cell functions such as proliferation and migration, and reported that cell migration was more greatly inhibited by serum from old donors than cell proliferation [1]. Moreover, since dietary restriction has been reported to extend lifespan and slow the aging rate of some animals [2], we wondered whether sera from dietary restricted and control monkeys of various ages might exhibit reduced aging effects on cell migration. When serum from young adult (3-5 years old) monkeys was added to plain medium, the migration of human fetal skin fibroblasts was very strongly inhibited compared to FBS. Surprisingly, sera from adult (6-11 years old) and old (more than 18 years old) monkeys caused significantly less migration-inhibitory activity than serum from young adult monkeys although sera from adult and old monkeys were much more inhibitory to cell migration than FBS. Dietary restriction only caused marginal effects on serum migration-promoting activity in a few monkey groups. The inhibition of cell migration caused by monkey serum was not brought about by cytotoxic effects since monkey serum stimulated cell proliferation as well as fetal bovine serum. These results indicate that the effects of aging on monkey serum migration-promoting activity are much more pronounced than those of dietary restriction.

Aging↗