International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management.

OBJECTIVES: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). METHODS: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit-harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. RECOMMENDATIONS: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

Interventions Against Disability in Frail Older Adults: Lessons Learned from Clinical Trials.

As the population ages, the number of older people with frailty is expected to increase worldwide with consequent rising of expenditures for healthcare and long-term care. Effective methods for preventing or delaying the onset of disability are urgently required. Frailty is a common and important geriatric condition characterized by age-associated declines in multiple physiological mechanisms, leading to increased vulnerability to stressors and higher risk for adverse health outcomes. Significant advancements have been made in the understanding of the frailty pathophysiological background. Given its multidimensional nature, reversing frailty requires a comprehensive approach. In this context, several studies testing the effects of pharmacological approach, physical activity, nutritional intervention, or cognitive training showed evidence of efficacy in frail older adults. Important innovations in ongoing trials include the development of multidomain interventions. Challenges include the use of trial designs, the development of standardized, sensitive outcome measures, and the need for interventions that can be implemented in resource-poor settings. In this viewpoint paper, based on recent literature, our aim was to identify relevant studies performed to reverse or delay disability in frail older adults.

Vitamin D supplementation in older adults: searching for specific guidelines in nursing homes.

BACKGROUND: The prevalence of vitamin D insufficiency is very high in the nursing home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated despite of strong clinical evidence and recommendations for supplementation. This review aims at reporting the current knowledge of vitamin D supplementation in NH and proposing recommendations adapted to the specificities of this institutional setting. DESIGN: Current literature on vitamin D supplementation for NH residents was narratively presented and discussed by the French Group of Geriatrics and Nutrition. RESULT: Vitamin D supplementation is a safe and well-tolerated treatment. Most residents in NH have vitamin D insufficiency, and would benefit from vitamin D supplement. However, only few residents are actually treated. Current specific and personalized protocols for vitamin D supplementation may not be practical for use in NH settings (e.g., assessment of serum vitamin D concentrations before and after supplementation). Therefore, our group proposes a model of intervention based on the systematic supplementation of vitamin D (1,000 IU/day) since the patient's admission to the NH and throughout his/her stay without the need of a preliminary evaluation of the baseline levels. Calcium should be prescribed only in case of poor dietary calcium intake. CONCLUSION: A population-based rather than individual-based approach may probably improve the management of vitamin D insufficiency in the older population living in NH, without increasing the risks of adverse health problems. The clinical relevance and cost effectiveness of this proposal should be assessed under NH real-world conditions to establish its feasibility.

Focal activation of the feline retina via a suprachoroidal electrode array.

This paper presents the results of the first investigations into the use of bipolar electrical stimulation of the retina with a suprachoroidal vision prosthesis, and the effects of different electrode configurations on localization of responses on the primary visual cortex. Cats were implanted with electrodes in the suprachoroidal space, and electrically evoked potentials were recorded on the visual cortex. Responses were elicited to bipolar and monopolar stimuli, with each stimulating electrode coupled with either six-return electrodes, two-return electrodes, or a single-return electrode. The average charge threshold to elicit a response with bipolar stimulation and six-return electrodes was 76.47+/-8.76 nC. Bipolar stimulation using six-return electrodes evoked responses half the magnitude of those elicited with a single or two-return electrodes. Monopolar stimulation evoked a greater magnitude, and area of cortical activation than bipolar stimulation. This study showed that suprachoroidal, bipolar stimulation can elicit localized activity in the primary visual cortex, with the extent of localization and magnitude of response dependent on the electrode configuration.

Implantation of episcleral electrodes via anterior orbitotomy for stimulation of the retina with induced photoreceptor degeneration: an in vivo feasibility study on a conceptual visual prosthesis.

BACKGROUND: A visual prosthesis is a conceptual device designed to harnesses the function of residual afferent neurons in the visual pathway to produce artificial vision. Such implant, when applied to stimulate the vitreous surface of the retina, has proven feasible in producing the perception of light in both animals and humans. However the practicality of such device has been challenged by the difficulty of surgical access and the risks of damaging the neuroretina. Positioning a visual implant over the scleral surface of the eye could present a safer alternative but this stimulation modality has not been tested in diseased retinas and little is known about the altered electrophysiological properties of the retina in influencing the feasibility of such approach. METHODS: Experimental photoreceptor degeneration was induced in four pigmented rabbit eyes with systematic administration of a retinotoxic agent, sodium iodate. A multielectrode array was implanted onto the surface of the sclera to target the central and peripheral parts of the retina via an anterior orbitotomy approach. The efficacy of retinal stimulation was assessed by recording electrical evoked potential over the primary visual cortex. FINDINGS: The electrical evoked potentials were obtained from both injected and control eyes. The charge density thresholds were found to be similar in both groups and were below the bioelectric safety limit. Spatially differentiated cortical activation profiles were obtained from the central and peripheral retina and the pattern of activation corresponded to the retinotopography of the rabbit primary visual cortex. CONCLUSION: This study proves that episcleral stimulation of the retina is a feasible alternative to intraocular approaches for the development of a visual prosthesis for retinas with photoreceptor loss.

Efficacy of supra-choroidal, bipolar, electrical stimulation in a vision prosthesis.

The key to successful, clinical application of therapeutic neurostimulators lies primarily with the safety and efficacy of their electrode-tissue interfaces. The authors posit that for electrical stimulation of the visual system, supra-choroidal electrode placement provides a safe, stable and readily-accessible site for implantation and the provision of electrical stimulation. The present paper explores the efficacy of supra-choroidal electrical stimulation of retinal neurons. Based upon recordings made with surface electrodes placed on the primary visual cortex, areas of activation in the cortex were shown to change when different areas on the supra-choroidal space were stimulated. Finally, the threshold to elicit a response from neurons in the visual cortex, was found to be 77.55 +/- 29.85 nC.

Systemic inflammatory markers in older persons: the effect of oral nutritional supplementation with prebiotics.

OBJECTIVE: To evaluate the effect of oral nutritional supplementation with and without oligosaccharides on gut bacteriology, in particular the bifidogenic flora, and on immunology and inflammatory parameters in older persons at risk of malnutrition. DESIGN: Prospective, randomized, double-blind, controlled study. SETTING: Division of Geriatric Medicine, St. Louis University, Missouri, United States. PARTICIPANTS: Seventy-four community dwelling elderly and/or nursing home subjects (age superior 70 y; 84 +/- 7 years) either undernourished or at risk of undernutrition. INTERVENTION: Daily liquid supplements, with (1.3 g/250 ml) and without oligosaccharides (OS) for 12 weeks. MEASUREMENTS: Nutritional evaluation, serum immunoglobulins, lymphocyte subsets, various cytokines and the endotoxin soluble receptor CD14 (sCD14) in serum, and cytokines specific mRNA in peripheral blood mononuclear cells at baseline and 12 weeks, and fecal bacteriologicy. RESULTS: Specific mRNA extracted from blood leucocytes showed a different level of pro-inflammatory gene activation: TNF-alpha mRNA and IL-6 mRNA diminished in the OS group after 12 weeks, while no changes were detected in the control group (P=0.05 and P=0.04 respectively). Serum levels of sCD14, a product shed by activated macrophages, decreased only in the OS group without reaching statistical significance (P=0.08). No significant differences were detected in the fecal gut flora or in the nutritional parameters. CONCLUSIONS: This study shows that the administration of supplements in older persons at risk of malnutrition may benefit from the addition of prebiotics that can improve the low noise inflammatory process frequently observed in this population.

The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics.

BACKGROUND: Previous studies reported that administration of first generation alpha-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP-1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP-1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger, increase satiation and limit food intake. OBJECTIVES: This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side-effects, on the regulation of meal-related GLP-1 secretion and on the change of insulin-glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured. DESIGN: In total, 8 obese type-2-diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double-blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption. RESULTS: The plasma GLP-1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP-1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects. The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo. The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period. In the miglitol-treated condition, the average caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the placebo-treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test. CONCLUSIONS: Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients.

Defining 'relative' androgen deficiency in aging men: how should testosterone be measured and what are the relationships between androgen levels and physical, sexual and emotional health?

In men, bioavailable and free testosterone levels decline by about 1.0 and 1.2% per year, respectively, after the age of 40. The definition of clinically relevant androgen deficiency in the aging male remains uncertain. Clinical features common to both aging and androgen deficiency include decreased muscle mass and strength, and increased fatigue, increased fat mass, loss of libido, erectile dysfunction, impaired cognitive function and depression. It is, however, difficult to separate the effect on plasma testosterone of concomitant disease, compared with the effects of a decrease in testosterone levels alone. Testosterone supplementation has been shown to be effective in improving many of the clinical features of androgen deficiency in the older male, and is safe, at least in the short term. The maximum benefit occurs in those men with the lowest testosterone levels.

Effect of metformin on nitric oxide synthase in genetically obese (ob/ob) mice.

Genetically obese (ob/ob) mice were employed for the study of the effect of metformin on activity and expression of nitric oxide synthase (NOS ) in vitro and in vivo. For in vitro analysis, mouse liver extracts were used. For the in vivo study, (ob/ob) and their control litter mates (ob/c) mice were injected with specified amounts of metformin and the expression of NOS in the adipose tissue and hypothalamus was measured by Western blotting. Results show that metformin exhibited a biphasic effect on NOS activity in vitro. Expression of metformin was differentially altered in the hypothalamus and adipose tissues of the normal and ob/ob animals that were treated with metformin. Further, a significant decrease in food intake occurred in the (ob/ob) mice that received metformin. This decrease in food intake was not accompanied by changes in serum glucose. At inhibitory concentrations, hypothalamic NOS expression changes differentially in normal and ob/ob mice. In normal mice, metformin stimulated NOS expression, while in ob/ob mice there was an inhibition. NOS expression increased in brown adipose tissue of metformin treated control mice, while no such increase was observed in ob/ob mice. No effect of metformin was observed in white adipose tissue of control or obese mice. Thus, metformin may produce anorectic effects through modulation of NOS.

Regional transport of TNF-alpha across the blood-brain barrier in young ICR and young and aged SAMP8 mice.

The blood-brain barrier (BBB) controls the exchange of regulatory substances, including tumor necrosis factor-alpha (TNF), between the brain and the blood. Transport across the BBB of some regulatory substances is altered with aging. Here, we measured the blood to brain unidirectional influx rate (Ki) for whole brain and 10 brain regions for radioactively labeled TNF in three groups of mice: young (2 mo old) ICR (the standard outbred albino laboratory mouse also termed CD-1), young SAMP8 (a strain which develops impaired learning and memory with aging that correlates with an age-related increase in brain levels of amyloid beta protein), and aged (17 mo) SAMP8 mice. In ICR mice, the hypothalamus had the fastest (1.73 microl/g-min) and the parietal cortex the slowest (0.189 microl/g-min) rates of uptake, a regional difference of about 9 fold. No differences in transport into whole brain or brain regions occurred between the ICR and young SAMP8, showing a lack of differences between strains. Transport was higher for the occipital cortex, midbrain, and striatum in aged SAMP8 mice. These results show blood-borne TNF enters some regions of the brain much more readily than others and TNF transport is increased into some brain regions of the SAMP8 mice at an age when learning and memory are impaired.

A case study of misrepresentation of the scientific literature: recent reviews of chiropractic.

Accurate use of published data and references is a cornerstone of the peer-review process. Statements, inferences, and conclusions based upon these references should logically ensue from the data they contain. When journal articles and textbook chapters summarizing the safety and efficacy of particular therapies or interventions use references inaccurately or with apparent intent to mislead, the integrity of scientific reporting is fundamentally compromised. Ernst et al.'s publication on chiropractic include repeated misuse of references, misleading statements, highly selective use of certain published papers, failure to refer to relevant literature, inaccurate reporting of the contents of published work, and errors in citation. Meticulous analysis of some influential negative reviews has been carried out to determine the objectivity of the data reported. The misrepresentation that became evident deserves full debate and raises serious questions about the integrity of the peer-review process and the nature of academic misconduct.

Effects of aging on the opioid modulation of feeding in humans.

OBJECTIVES: To determine whether aging is associated with a reduction in the opioid modulation of feeding, which may be important in the pathogenesis of the "anorexia of aging." DESIGN: Three studies on separate days, in randomized order and double-blind fashion. SETTING: Clinical Human Research Laboratory, Department of Medicine, RAH, Adelaide, Australia. PARTICIPANTS: Twelve older (5 male/7 female) (age 65-84) and 12 young (5 male/7 female) (age 20-26) healthy subjects. INTERVENTION: Subjects received in double-blinded random order, intravenous bolus (10 minutes) and then continuous (140 minutes) infusions of saline (control), naloxone low dose (LD) (bolus 27 microg/kg; continuous 50 microg/kg/hr), or naloxone high dose (HD) (bolus 54.5 microg/kg; continuous 100 microg/kg/hr). MEASUREMENTS: After 120 minutes, subjects were offered a buffet meal, and their energy intake was quantified. Hunger, fullness, nausea, and drowsiness were assessed using visual analogue scales. RESULTS: The naloxone LD and HD infusions had no significant effect on ratings of hunger, fullness, or nausea, but increased drowsiness (P < .01) compared with the control infusion in both age groups. Older subjects ate less (P < .001) at the buffet meal than young subjects during all three infusions. Naloxone infusions reduced energy intake compared with control (P < .001), LD by 13.2 +/- 5.0% and HD by 10.7 +/- 5.0%, with no difference between the doses (P = .71). Overall, naloxone suppressed energy intake in both young and older subjects (P < .01). This suppression was slightly, but not significantly, greater in young than in older subjects (mean of LD and HD 16.4 +/- 4.9% vs 7.5 +/- 4.9%, P = .42), because of a trend to reduced suppression in older women. CONCLUSIONS: We conclude that healthy older adults retain their sensitivity to the suppressive effects of naloxone on food intake. Possible gender differences in this sensitivity warrant further investigation. A decline in opioid activity is unlikely to contribute substantially to the physiological anorexia of aging observed in older people.

Polypharmacy and hospitalization among older home care patients.

BACKGROUND: One of the major goals of home care is the prevention of hospitalization. The objective of this study was to examine the relation between medication use (number, type, and inappropriateness) and hospitalization among home care patients older than 65 years. METHODS: A retrospective chart review of 833 discharged older home care patients was performed. These patients were consecutive discharges from a single home care agency who either (a) returned to independent self-care or care of the family (S/F Care group) or (b) were admitted to the hospital (Hospitalized group). Medication assessment within these two groups included total number of medications (prescription and nonprescription); degree of polypharmacy (percentage of patients taking 5 or more, 7 or more, and 10 or more medications); and prevalence for different types of medications, including different types of inappropriate medications. Inappropriate medications were designated according to a list that was previously developed through a modified Delphi consensus technique by a panel of 13 experts in geriatric pharmacology and has been utilized in other studies. Student's t test was used for continuous variables and chi-square test was used for categorical variables to evaluate for differences between the S/F Care group and the Hospitalized group (p <.05). For comparisons of types of medications, p < .01 was used for significant differences, because of the high number of comparisons made. RESULTS: Of 833 discharges, 644 (77.3%) returned to self-care or care of the Family (S/F Care group) and 189 (22.7%) were hospitalized. The Hospitalized group, compared with the S/F Care group, was taking a higher number of medications (mean +/- SD: 6.6+/-3.9 vs 5.7+/-3.4, p = .004), and had a higher percentage of patients taking 7 or more medications (46% vs 26%, p = .002) and 10 or more medications (21% vs 10%, p = .005), but not 5 or more medications. Only three types of medications were more commonly used among patients in the Hospitalized group than among patients in the S/F Care group: clonidine (4.2% vs 1.1%, p = .004); mineral supplements (23.8% vs 14.8%, p = .003); and metoclopramide (5.8% vs 2.0%, p = .006). The Hospitalized group had a lower percentage of patients taking inappropriate medications than did the S/F Care group (20% vs 27%, p = .040), but none of the types of inappropriate medications was used more often in either group. CONCLUSIONS: This study shows a relationship between high levels of polypharmacy and hospitalization. Although it cannot be determined from this study whether a higher number of medications was an indicator of sicker patients at risk for hospitalization, or whether a higher number of medications might have directly led to hospitalization, polypharmacy should still be considered a marker for older home care patients for whom prevention of hospitalization is the goal.

Longitudinal changes in serum 25-hydroxyvitamin D in older people.

Cross-sectional studies have suggested that serum 25-hydroxyvitamin D (25OHD) levels decline with aging. We have examined this putative decline in a longitudinal study using participants in the New Mexico Aging Process Study. 25OHD levels were measured in participants in whom serum samples were available between 1980 to 1982 and 1989 to 1994 (37 men and 99 women). The available data for these visits included age, gender, and the date the sample was obtained. Questionnaires assessing physical activity and vitamin D intake were administered at the visits. A seasonal variation (r = .25, P < .05) in 25OHD was demonstrated in the whole group of subjects. In 25 subjects who were not receiving vitamin D supplementation at either time and had samples obtained in the same season, both serum 25OHD (P < .05) and physical activity (P < .05) decreased over a mean period of 11.4 years. In 23 subjects who had samples obtained in the same season but used vitamin D supplements at both times, there was no change in serum 25OHD. Mean summer 25OHD levels did not change with the duration of study. On the other hand, the mean serum 25OHD declined with the duration of study when measured from winter to winter or spring to spring. Multiple regression analysis demonstrated that the month, activity level, vitamin D supplementation, and gender (P < .001) were independent determinants of serum 25OHD levels. This study confirms that aging is associated with a reduction in serum 25OHD, and suggests that this decrease is a reflection of reduced sun exposure rather than aging per se. The reduction in serum 25OHD was the result of decreasing winter and spring 25OHD serum concentrations. It is clear that vitamin D supplementation can prevent the age-related decline in 25OHD levels.