Significant Age-related Decrease Research Articles

Antioxidant systems in rat lens as a function of age: Effect of chronic administration of vitamin E and ascorbate

Oxidative damage occurring in the lenses of patients with senile cataract may be due to partially reduced forms of oxygen. We assayed the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Red), and glucose-6-phosphate dehydrogenase (G6PD) in rat lenses at different ages (1, 4, and 24 months), and also evaluated lens glutathione (GSH) levels and the effects of chronic administration of vitamin E and sodium ascorbate. We observed a significant age-related decrease in GSH-Px, GSH-Red and G6PD activities, but no age-related change in SOD activity. Chronic treatment with both vitamin E and sodium ascorbate failed to restore enzymatic activities to the levels of younger rats. An age-related reduction in GSH content was also observed; however, chronic administration of vitamin E, but not of sodium ascorbate, restored GSH levels to those of younger rats.

Regional distribution of subtypes of nicotinic receptors in human brain and effect of aging studied by [formula omitted

Epibatidine, a potent nicotinic agonist, was used to study the regional distribution of nicotinic acetylcholine receptor binding sites in the human brain. Saturation studies performed in the human temporal cortex with (±)-[ 3 H] epibatidine revealed binding to two binding sites with K d and B max values of 0.018 and 4.2 nM, 12.7 and 15.4 fmol/mg protein, respectively. Competition studies with (±)-[ 3 H] epibatidine/unlabelled nicotine or [ 3 H] nicotine/unlabelled (±)-epibatidine showed binding to two binding sites in the human temporal cortex ( K i=0.16 and 12.6 nM; 0.007 and 0.3 nM, respectively). Similarly, when unlabelled nicotine was used to displace (±)-[ 3 H] epibatidine , two binding sites were also revealed in the thalamus and the cerebellum of human brain ( K i=0.065 and 7.7 nM; 0.07 and 12.5 nM, respectively). The regional binding of (±)−[ 3 H] epibatidine binding in human brain was somewhat different from that of [ 3 H] nicotine . A proportionally higher binding was observed for (±)-[ 3 H] epibatidine in the cerebellum and the thalamus compared to [ 3 H] nicotine , probably reflecting different selectivity to nicotinic receptor subtypes. A marked significant age-related decrease in (±)-[ 3 H] epibatidine binding was observed in the frontal and the temporal cortices (−79%, −84%, respectively) of human subjects between 56–85 years of age, which was similar to that of [ 3 H] nicotine (−82%, −79%, respectively). The (±)-[ 3 H] epibatidine binding in the cerebellum decreased significantly with age (−77%), while [ 3 H] nicotine binding showed no significant age-related changes in this brain region. The findings indicate that a specifically modulate regional nicotinic receptors in human brain.

Checkpoints in thymocytopoiesis in aging: expression of the recombination activating genes RAG-1 and RAG-2

The study was designed to establish whether the ability to rearrange the T cell receptor (TCR) V β genes is altered with age. We examined the expression of recombinase activating genes, RAG-1 and RAG-2, in the thymus of mice at different ages (2–24 months). A significant age-related decrease in RAG-1 and RAG-2 expression was observed in the thymocytes from the age of 12 months and over. To find out if this decrease is determined in the thymocyte progenitors or induced by the thymic microenvironment, we co-cultured lymphoid depleted fetal thymus (FT) explants with bone marrow cells, or immature thymocytes, from young and old mice. The developing thymocytes were examined at different time intervals during the first week of culture. Whereas cells derived from the immature thymocytes of the old donors failed to express RAG-1 and RAG-2, compared to the young, the bone marrow derived cells of both age groups did show this expression, and there was no difference in V β rearrangement of the TCR. Our study indicates that T cell progenitors in the aging bone marrow retain the potential to give rise to T cells with TCR rearrangements, and the expression is determined by the thymic stroma.

Chemosensory event-related potentials change with age

The study examined age-related changes in the perception of olfactory and trigeminal chemical stimuli using chemosensory event-related potentials (CSERP). Three groups of healthy volunteers, each comprised of 8 men and 8 women, were tested (age ranges 15–34, 35–54, and 55–74 years). Subjects underwent extensive psychological testing focusing on impairments of memory and attention. In addition, odor identification and discrimination ability was evaluated, as well as detection threshold sensitivity for two odorants. Odor discrimination scores exhibited a significant age-related decrease. Significant age-related changes were also observed for CSERP N1P2 and P2 amplitudes, and for the N1 peak latency. The age-related decrease of CSERP amplitudes appeared to follow a different time course for responses to trigeminal and olfactory stimulants.

Urinary excretion of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid in children.

5-S-Cysteinyldopa (5SCD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) are formed during biosynthesis of melanins. They are used as indicators of pigment formation and markers of melanoma progression in adults and could possibly be used as markers of activity, growth and even malignant transformation in large pigmented naevi in children. We investigated the urinary excretion of these pigment precursor metabolites from 136 children, 5 to 15 years of age. The mean 5SCD excretion was 38.1 mumol/mol creatinine. A significant age-related decrease from a mean of 60.4 mumol/mol creatinine at 5 years of age to 28.0 mumol/mol creatinine at age 15 was found. In a reference group (29 adults, 20-33 years of age) the mean excretion was 48.9 mumol/mol creatinine. The mean excretion of 6H5MI2C was 42.8 mumol/mol creatinine at 5 years of age and 26.1 mumol/mol creatinine at the age of 15. The mean value for the young adults was 33.4 mumol/mol creatinine. No correlation between the mean excretion of 5SCD and 6H5MI2C was demonstrated. We suggest an upper reference level of 90 mumol/mol creatinine for the excretion of 5SCD in the age group 5-11 years and of 60 mumol/mol creatinine in the age group 13-15 years. Corresponding figures for the indole 6H5MI2C are 70 and 60 mumol/mol creatinine. The establishment of reference values in children will make it possible to use 5SCD and 6H5MI2C measurements as diagnostic tools, indicating growth or malignant transformation in giant melanocytic naevi during childhood.

Variations in trabecular bone composition with anatomical site and age: potential implications for bone quality assessment

Skeletal site-related differences in trabecular bone composition have been studied in autopsy samples from 63 individuals (age range 23-92 years). From each individual, bone samples were excised from the iliac crest, lumbar spine, femoral neck, and calcaneus. Samples were analyzed for their content of ash, calcium, collagen, extractable proteins, osteocalcin, and IGF-I. Significant differences were found between the skeletal sites, the lumbar spine being the least mineralized site and the femur the most. The femur and lumbar spine had a higher osteocalcin and IGF-I content compared with the other skeletal sites, suggesting a higher bone turnover rate. The intercorrelations between the anatomical sites were low for minerals and collagen but high for osteocalcin and IGF-I. The latter might indicate that the presence of these proteins in the bone matrix is mainly controlled by endocrine mechanisms which may influence the osteoblast function. Finally, regression analysis showed a significant age-related decrease of skeletal IGF-I at all sites examined. This finding supports the hypothesis of an IGF-I-mediated pathogenesis of senile osteoporosis. In summary, our data imply that a global assessment of skeletal function and bone quality, based upon analyses at one anatomical site, should be applied with caution.

A model of oxygen transport capacity changes for independently living older men and women.

The purpose of the present investigation was to describe, for a subset of a large random survey of men and women, restricted to the ages of 55 to 85 years, the physiological decay pattern for aerobic fitness and contributing factors of cardiovascular and pulmonary function. The time course of the age-related changes in maximal oxygen uptake (VO2max), ventilatory threshold (TVE), maximal ventilation (VEmax), maximal heart rate (HRmax), and O2 pulse (VO2max/HRmax) were examined by fitting the data to a decaying exponential model by use of a least-squares parameter estimation technique. The time constant (tau) was used to describe the rate of decline. The women showed a much slower decline in VO2max (tau = 47.4 years) and TVE (tau = 83.3 years) than the men (tau = 20.8 and 15.4 years, respectively). There was a significant age-related decrease in body weight (0.45 kg.yr-1) in the men, whereas the women showed no change. Pulmonary function did not limit performance based on the very slow decline in VEmax and the normal FEV1.0. The decay in HRmax was better described by a linear model, resulting in an extremely slow tau. Maximal O2 pulse clearly exhibited an exponential decay, with a shorter tau (tau men = 13.5 years; tau women = 28.5 years) than any other variable.

Fluctuating Asymmetry and Isozyme Variation in Atlantic Salmon: Relation to Age of Wild and Hatchery Fish

Abstract Isozyme variation and fluctuating asymmetry at different ages of Atlantic salmon Salmo salar were analyzed for hatchery and wild stocks. Significant age-related decrease of fluctuating asymmetry was detected in wild stocks but not in hatchery stocks. Natural selection may act against phenotype asymmetry, or some trait associated with asymmetry, in wild but not in hatchery populations. Heterozygosity did not vary significantly with fish age in most cases, suggesting the lack of association between heterozygosity and asymmetry.

Decreased duration of Ca(2+)-mediated plateau potentials in striatal neurons from aged rats.

1. The influence of age on striatal neuron Ca2+ physiology was studied through an analysis of intracellularly recorded Ca(2+)-mediated plateau potentials. In vitro brain slices from young and aged rats were treated with the K+ channel blocker tetraethylammonium (30 mM) to facilitate the expression of plateau potentials. A sample of neurons was also filled with biocytin and post hoc correlations were performed between morphology and physiology. 2. Testing of sampling parameters in neurons from young rats revealed that tetrodotoxin did not affect the amplitude or duration of plateau potentials. The membrane potential induced during plateau testing and the rate of plateau potential generation, however, had to be held constant because these variables affected plateau potential duration. 3. A significant age-related decrease was found in the duration of Ca(2+)-mediated plateau potentials that could not be explained by alterations in the activation or inactivation properties of the plateau potential. Investigation into relationships between cell morphology and plateau potential duration revealed a number of correlations. Soma size and dendritic length were correlated with plateau potential duration, independent of age (hierarchical regression), and an age-related decrease in dendritic length but not in soma size was found. Spine density and plateau potential duration were also correlated, but the significance depended on the variance associated with age. These data indicate that the extent of somadendritic membrane (including spines) affects plateau potential duration in striatal neurons and that dendrite and spine loss in aged animals may contribute to age-related decreases in plateau potential duration. 4. The response to replacement of Ca2+ with Ba2+ was age dependent, with Ba2+ causing a greater increase in the duration of plateau potentials in young neurons. These data rule out an increase in Ca(2+)-mediated inactivation of Ca2+ channels as a primary cause for the shortening of plateau potentials in aged neurons. Our morphological findings suggest that dendritic regression in aged neurons may have reduced the number of Ca2+ channels participating in plateau potential generation, but other mechanisms related to changes in the type of Ca2+ channel expressed and possible differences in their inactivation kinetics may also contribute to the age-related change in plateau potential duration.

Growth of the cervical spine with special reference to its lordosis and mobility.

The cervical spine of the healthy Japanese children aged between 1 year and 18 years was radiographically examined. To examine the correlation between growth of the cervical vertebral body and the facet joint and the development of the cervical lordosis and intervertebral motion. Although the growth of body height and facet angle have been well documented, their correlation with curvature or mobility has not been elucidated. We evaluated plain lateral radiographs of 180 boys and 180 girls regarding diameters and central heights of the cervical vertebra, the anterior and posterior vertebral height ratio, body height index, the facet joint angles, and tilting and sliding motions. Cervical length as the summation of the central height from C3 to C7 and the cervical lordosis angle (C3-C7 angle) were also measured. The mean C3-C7 angle and body height index gradually decreased until 9 years of age and then increased. The C3-C7 angle showed a significant correlation with cervical length, body height index, and facet joint angles before 9 years of age, and with cervical length and body height index after 9 years of age but not with facet joint angles. Facet joint angle decreased until 10 years of age and remained almost unchanged thereafter. Total sliding showed a significant age-related decrease and showed a significant correlation with facet joint angle. Although the lordosis angle showed a significant correlation with the other values, cervical length, body height index, and facet joint angle, the determinants of the lordosis could not be elucidate in the present study. As for the mobility of the cervical spine, changes of tilting motion were small, whereas changes of sliding motion were restricted by the change of orientation of the facet joints.

Alterations of brain insulin receptor characteristics in aging mice.

An interesting role of insulin and insulin receptors (InsRs) in the brain is neuromodulation of monoaminergic systems. Since our previous studies showed age-dependent alterations of alpha- and beta-adrenoceptors in mouse brain cortex, the intriguing role of brain InsRs per se and their involvement in adrenergic modulation prompted us to check their eventual changes with aging. Thus, brain InsR characteristics were studied in young (3 months) and old (27 months) Balb/c-nu mice by direct binding with (125)I-insulin. A two-sites model analysis of data shows a statistically significant age-related decrease of receptor density (39%) and k(d) (57%) in the high affinity population. The low affinity receptor subset also shows a decreasing trend of its characteristics; however, differences are not statistically significant and show a high degree of interindividual variability in both groups of mice.

ASSOCIATION OF SOCIO-DEMOGRAPHIC VARIABLES TO PHYSICAL ACTIVITY LEVELS IN ADOLESCENTS: ANALYSIS OF 1992 YRBS DATA 193

Two physical activity recommendations for adolescents have recently been formulated by an international panel of experts: 1) adolescents should ideally have some type of physical activity on a daily basis and 2) they should perform at least 20 minutes of more moderate to vigorous activity a minimum of 3 days per week. We hypothesize that social and physical environments may have a significant influence on physical activity levels for many youth. Thus, we analyzed data for a sub-sample of 12-17 year old adolescents (n=6.496) from the 1992 National Health Information Survey (NHIS)-Youth Risk Behavior Survey(YRBS), in order to look at the association of six socio-demographic variables to the attainment of this second guideline. In the YRBS the item “took part in activites that caused sweating/hard breathing in the past week” is a proxy for engaging in sustained activities of moderate to vigorous intensity. For the purposes of this analysis the dependent variable was dichotomized into “reaching/not reaching” the recommended level(≥3 days). The six independent variables were age (12-14 years versus 15-17 years); race (white versus non-white); level of family income (above or below poverty level); educational level of the parents (≤ high-school education versus >high-school); family structure (living with 2 parents versus“other”; ie. single parent); and the type of living quarters(house/apartment versus “other”). Results of a multiple logistic regression (OR, 95% C.I.) showed a significantly greater likelihood of reaching the recommended guideline for those adolescents younger than 15 1.6(1.4, 1.7), living with 2 parents 1.2 (1.0, 1.3), having parents with a higher than high-school education 1.3 (1.2, 1.4) or being in a family with income above the poverty level 1.2 (1.1, 1.4). Neither racial status nor the type of living quarters resided in was associated with the outcome. More studies are needed to gain a greater understanding of those socio-demographic factors which are critical in influencing adolescent physical activity, such as the significant age-related decrease in activity seen in this analysis.

Aging and saliva: A review of the literature

It is often assumed that salivary secretion reduces with age. About 25% of the elderly suffer from oral dryness and related complaints. Nevertheless, data on stimulated salivary flow rate in healthy elderly revealed no significant age-related decrease other than a slight decrease of the secretion from the (sero)mucous glands under conditions of minimal or extended stimulation. With regard to salivary gland morphology and composition of saliva, age-related changes have been reported in healthy individuals, too. With increasing age, the number of acini reduces and the amount of fatty and fibrous tissue increases. Moreover, animal studies revealed that the synthesis of proteins is reduced by 60% in advanced years. These data indicate that changes might occur in concentration and/or activity of the organic components of saliva. In human studies, the concentration of sIgA in labial saliva and the concentrations of high-molecular and low-molecular mucins in mucous saliva appeared to be reduced with age. Since sIgA and mucins are important in the immunologic and non-immunologic defense of the oral cavity, both defense systems are reduced in healthy elderly. Analysis of these data suggests that the oral soft tissues may become somewhat more susceptible to environmental factors due to a reduction of the immunological and non-immunological defense systems.

Muscarinic receptors in developing rat colon

Muscarinic receptor subtypes were characterized in fetal (21 day), newborn (3 day), and adult (3 month) rat colon smooth muscle. Saturation binding of the nonselective muscarinic antagonist radioligand [ 3H]quinuclidinyl benzilate revealed a single class of binding sites in all three age groups. The binding affinities of [ 3H]quinuclidinyl benzilate were not significantly different among three age groups ( K D: 0.19 → 0.27 nM). In contrast, the receptor densities ( B max, fmol/mg protein) showed a significant age-related decrease with fetus (518.9 ± 7.4) > newborn (480.3 ± 45.6) ⪢ adult (192.4 ± 32.8). In both newborn and adult tissues, the muscarinic agonist carbachol bound to two sites with high and low affinities. Although the agonist binding affinities in the newborn tissue were not significantly different from those in the adult tissue, the high-affinity binding sites for carbachol were significantly increased in the later (41% → 61%). Addition of guanosine-5′- O-(3-thio)triphosphate (100 μM) abolished apparent high-affinity binding sites in both newborn and adult tissues. Antagonist competition binding in the newborn tissue indicated a homogeneous population of muscarinic M 2 receptors. Unlike in newborn tissues, the heterogeneous binding of pirenzepine and 4-diphenylacetoxy- N-methylpiperidine methobromide in adult tissues revealed coexistence of muscarinic M 3 (45%) and M 2 (55%) receptors. In accordance, activation of muscarinic receptors in the adult tissue stimulated synthesis of inositol 1,4,5-trisphosphate. These results suggest maturational changes of muscarinic receptor subtypes and their coupling to G proteins in rat colonic smooth muscle. These changes may account, at least in part, for developmental alterations of functional responses in colonic smooth muscle.

Cardiovascular parameters: sensitivity to detect autonomic dysfunction and influence of age and sex in normal subjects.

In 137 healthy volunteers between 18 and 85 years of age, blood pressure (BP) and heart rate (HR) were measured continuously with the Finapres device during active change of posture (ACP), i.e. standing upright, passive tilt (PT, i.e. head-up tilt), Valsalva manoeuvre (VM), deep breathing (DB), isometric muscle exercise (IME) and a mental arithmetic task (MA). Mean HR activation was attenuated with increasing age in all manoeuvres, but was unrelated to sex. In non-orthostatic challenge procedures like MA and IME mean BP increases were independent of age and sex, despite lower increases in HR in the elderly. This points to a preserved sympathetic efferent activity. Following a forced fall in BP during ACP, PT and VM, the initial responses and maintenance values of BP showed a significant age-related decrease. This finding was strongly related to lower BP values in males compared with females, which became more pronounced with increasing age. Further studies to investigate age-related changes in the activation of the various components of the cardiovascular regulation need to consider the mode of activation of the autonomic nervous system and sex as factors of influence. Normal ranges, and also some new points in time not previously measurable, were calculated for all standard autonomic tests based on the continuous measurement of BP and HR. The minimum length of time necessary to assess the cardiovascular responses during ACP and PT was found to be 60 s. The upper time limits for reaching maximum activation during IME and MA were 3.5 min and 1 min, respectively. Age had a relevant influence on the lower limits of normal of all HR parameters and of some BP measurements during PT, ACP and VM. Sex was found to have no relevant impact on normal ranges. Over 65 years of age the normal values for HR activation during VM and DB hardly exceeded baseline values. The possibility of increasing the sensitivity of detection of autonomic dysfunction by measuring BP continuously must be approached with caution, as sufficient sensitivity was only reached at the lower limits of normal during late phase II of the VM. The initial increase of HR after ACP and the BP values after 60 s standing time proved to be the parameters with the best sensitivity for detecting an affection of the regulation of HR and BP over the whole range of age.

Increased light intensity prevents the age related loss of vasopressin-expressing neurons in the rat suprachiasmatic nucleus

We investigated whether increased light input can counteract the age-related decrease in vasopressin- (AVP) and vasoactive intestinal polypeptide (VIP)-expressing neurons of the suprachiasmatic nucleus (SCN) by determining the numbers of these neurons in rats of different ages, housed under low or high intensities of light. The significant age-related decrease for AVP was prevented in old animals after high light housing. For VIP, no effects were found.

Age-related reduction of [3H]strychnine binding sites in the cochlear nucleus of the fischer 344 rat

The present study used quantitative receptor autoradiography to examine the effects of aging on the binding profile of the strychnine-sensitive glycine receptor in the Fischer 344 rat. Glycine receptor binding sites were localized using [3H]strychnine in two principal subdivisions of the cochlear nucleus; the dorsal and anteroventral cochlear nucleus. These central auditory brainstem structures are known to receive extensive glycinergic inputs. In young rats, single concentrations of [3H]strychnine showed significantly higher binding levels in the dorsal cochlear nucleus than the anteroventral cochlear nucleus (+38%, P < 0.001). Little binding was detected in regions of the posteroventral cochlear nucleus, and no specific binding was apparent in the cerebellum. Saturation analysis in the dorsal cochlear nucleus revealed an affinity constant (Kd) of 16.9 nM and a maximum number of binding sites of 850 fmol/mg protein. A significant age-related decrease in [3H]strychnine (8 nM) binding was observed in the anteroventral cochlear nucleus (-37%, P = 0.003) and dorsal cochlear nucleus (-23%, P = 0.034) of 26-month-old rats compared with three-month-old rats. Saturation analysis indicated that the observed decrease in binding was due to a decrease in the total number of binding sites with no significant change in affinity. In the dorsal cochlear nucleus, the number of binding sites was reduced (-26%) in 26-month-old rats compared with three-month-old adults (P = 0.011). Kd was decreased (-22%) in 26-month-old rats when compared with young adults, but this decrease was not statistically significant (P = 0.377).(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of benzazepine UDP-glucuronosyl-transferases in laboratory animals and man

1. The O-glucuronidation of two dopamine D1 receptor antagonists, Odapipam and Berupipam, were studied in hepatic microsomal fractions from mouse, rat, rabbit, dog, pig, and man using 14C-UDP-glucuronic acid. 2. The influence of pH, detergent, gender, drug-metabolizing enzyme inducers, and age were examined. Detergents like the zwitterionic CHAPS and non-ionic Tween 20, Triton X-100, and Brij 35 stimulated the glucuronidation rate by up to 600% of native activity with the latter being most effective. Both apparent Km and Vmax increased following detergent treatment in rat hepatic microsomes. Less marked activation of UDP glucuronosyltransferase activity was observed with Brij 35 in mouse, rabbit, dog, and pig compared with rat. In contrast, human hepatic microsomes were not stimulated by detergent treatment. 3. Marked species-dependent UDP-glucuronosyltransferase activity were observed for the two compounds. In general, Odapipam exhibited higher Vmax and Km compared with Berupipam with the exception of rabbit where the reverse was true. Similar kinetic parameters were, however, observed in human hepatic microsomes. Highest glucuronidation rate (in general) was observed in mouse followed by dog, pig, rabbit, man, and rat. 4. UGT activity in human livers showed up to a seven-fold variation. Conjugation of each compound were highly correlated (r = 0.92; n = 20) suggesting that identical isoform(s) were involved in this reaction. A significant age-related decrease in UDP-glucuronosyltranferase activity was observed, which partly could be explained by a preponderance in elderly female donor liver samples.

Bone histomorphometry in 50 normal Tunisian subjects.

Quantitative bone histomorphometry was done on undecalcified sections of iliac crest bone specimens obtained at autopsy from 50 normal subjects (24 males and 26 females). The following parameters were measured: cortical thickness (Ct.Th), trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), osteoid volume (OV/BV), osteoid surfaces (OS/BS), osteoid thickness (O.Th) and eroded surfaces (ES/BS). There was a significant age-related decrease in BV/TV in both sexes which followed a x3 polynomial regression. A significant decrease of Tb.Th was noted in males after the fifth decade. In males, bone loss was 1.5% per decade, but in females it was 0.36% before menopausal period and 2% after. Other parameters were unrelated to age and sex.

Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy

We studied mitochondrial respiratory chain function in skeletal muscle taken from 27 patients with idiopathic Parkinson's disease (PD; 21 Dopa-treated PD patients and 6 de novo patients), 5 patients with multiple system atrophy (MSA) and from 43 age-matched controls in order to determine the occurrence of mitochondrial respiratory chain abnormalities in parkinsonian syndromes. In our control subjects, we found a significant age-related decrease in the activity of respiratory chain complex I. As compared to carefully age-matched control subjects, activity of complex (NADH: ubiquinone reductase) was significantly lower in muscle mitochondria from patients with PD and MSA and a mean remaining activity < 30% of controls was observed. Mean activities of complexes III (ubiquinol:cytochrome c reductase) and IV (cytochrome c oxidase) were also lower in PD patients than controls, but a low activity (remaining activity < 30% of controls) was observed in only 5 PD patients for complex I and III or I and IV. No deficit in complex II activity (succinate: ubiquinone reductase) was observed. Our results support the hypothesis of a wide-spread mitochondrial complex I deficiency in PD and MSA as compared to age-matched controls, who showed age-related deficiency. This deficit can be found in de novo PD patients as well as in treated patients. The observed respiratory enzyme chain deficiency could not be explained by the dose and duration of l-Dopa or dopaminergic agonist treatment, the severity of the disease, anxiety or depression since no significant correlation was found between these parameters and enzyme complexes activities.