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Appetite loss/anorexia of aging is a highly prevalent and burdensome geriatric syndrome that strongly impairs the quality of life of older adults. Loss of appetite is associated with several clinical conditions, including comorbidities and other geriatric syndromes, such as frailty. Despite its importance, appetite loss has been under-evaluated and, consequently, under-diagnosed and under-treated in routine clinical care. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually on September 27th 2021 to debate issues related to appetite loss/anorexia of aging. In particular, topics related to the implementation and management of appetite loss in at-risk older adult populations, energy balance during aging, and the design of future clinical trials on this topic were discussed. Future actions in this field should focus on the systematic assessment of appetite in the care pathway of older people, such as the Integrated Care for Older People (ICOPE) program recommended by the World Health Organization. Moreover, clinical care should move from the assessment to the treatment of appetite loss/anorexia. Researchers continue to pursue their efforts to find out effective pharmacologic and non-pharmacologic interventions with a favorable risk/benefit ratio., Competing Interests: The Task Force was partially funded by registration fees from industrial participants. These corporations placed no restrictions on this work. Dr. Morley, Dr. Landi, Dr. Roberts, and Dr. Rolland declare no conflicts of interest related to this work; Dr de Souto Barreto reports consulting from Pfizer, outside the submitted work; Dr. Cederholm reports personal fees from Nutricia, personal fees from Abbott, personal fees from Fresenius Kabi, grants from Pfizer, outside the submitted work; Dr. Cesari reports personal fees from Nestlé Health Sciences, outside the submitted work; Dr. Vellas is an investigator in clinical trials sponsored by the Toulouse University Hospital (Inspire Geroscience Program); Dr Fielding reports grants from National Insitutes of Health, grants from USDA Agricultural Research Service, grants, personal fees and stock options from Axcella Health, stock options from Juvicell, stock options from Inside Tracker, grants and personal fees from Biophytis, personal fees from Amazentis, personal fees from Nestle, grants from Pfizer, outside the submitted work.

Previous evidence suggests physical activity interventions effectively produce short-term improvements in physical function for older adults. The present study examined whether improvements in physical function after a DVD-delivered exercise intervention were maintained 18 months postintervention. Older adults (n = 153) randomized to a 6-month DVD-delivered exercise intervention or an attentional control condition were contacted 18 months postintervention. Participants completed the Short Physical Performance Battery (SPPB) and measures of flexibility, strength, and functional limitations were taken. Analyses of variance were conducted to determine if improvements in physical function as a result of the intervention were maintained at follow-up. Improvements in the SPPB, F (1,125) = 3.70, p = .06, η 2 = .03, and upper body strength, F (1,121) = 3.04, p = .08, η 2 = .03 were maintained for the intervention condition. Home-based DVD exercise training interventions may hold promise for long-term maintenance of physical function in older adults.

- It is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. The underlying mechanisms of cellular senescence, while not fully understood, have been associated with telomere erosion, DNA damage, oxidative stress, and inflammation. In this review, we discuss the causes and consequences of cellular senescence, and the associated biological challenges in cartilage repair. In addition, we present novel strategies for modulation of cellular senescence that may help to improve cartilage regeneration in an aging population.

The extent of ageing in the musculoskeletal system during the life course affects the quality and length of life. Loss of bone, degraded articular cartilage, and degenerate, narrowed intervertebral discs are primary features of an ageing skeleton, and together they contribute to pain and loss of mobility. This review covers the cellular constituents that make up some key components of the musculoskeletal system and summarizes discussion from the 2015 Aarhus Regenerative Orthopaedic Symposium (AROS) (Regeneration in the Ageing Population) about how each particular cell type alters within the ageing skeletal microenvironment.

Animal studies have shown that life span is extended by caloric restriction (CR). This manuscript describes the design and methodology of an innovative CR intervention, which is the treatment arm of the CALERIE Study. This study is a multi-center, randomized controlled trial examining the effects of 2 years of CR on biomarkers of longevity among non-obese (BMI ≥ 22 kg/m(2) and <28 kg/m(2)) adults. CALERIE is the first investigation of the effects of long-term CR on the aging process in non-obese humans. 220 healthy volunteers across 3 sites were recruited beginning in May 2007. Participants were randomized in a 2:1 ratio between the CR or control group (i.e., ad libitum diet). An intensive intervention was designed to assist participants in adhering to the 25% CR prescription for a two-year duration. The intervention was designed to optimize the likelihood that 25% CR would be achieved through a variety of nutritional and behavioral strategies, several of which are innovative methods for achieving CR. The intervention includes the following components: an intensive, "mixed" format schedule of group/individual sessions, meal provision phase with exposure to various diets, Personal Digital Assistants to monitor caloric intake, unique portion estimation training, tailored treatment using a computer tracking system, toolbox strategies and algorithms, as well as comprehensive coverage of nutrition and behavioral topics in order to assist participants in meeting their CR goal. This manuscript provides an overview of the CR intensive intervention and may be of assistance for other researchers and clinicians in designing future trials., (Copyright © 2011 Elsevier Inc. All rights reserved.)

An outbreak of measles in another region of New Zealand prompted our organization to review the measles immunity of healthcare workers. Some studies suggest that age-specific immunity cannot be assumed. In our local setting, however, we found that 893 (98%) of 912 healthcare workers more than 40 years old tested seropositive for measles immunoglobulin G.

Summary: We have produced paediatric reference data for forearm sites using the Stratec XCT-2000 peripheral quantitative computed tomography scanner. These data are intended for clinical and research use and will assist in the interpretation of bone mineral density and bone geometric parameters at the distal and mid-shaft radius in children and young adults aged between 6-19 years., Introduction: Peripheral quantitative computed tomography (pQCT) provides measurements of bone mineral content (BMC), density (BMD) and bone geometry. There is a lack of reference data available for the interpretation of pQCT measurements in children and young adults. The aim of this study was to provide reference data at the distal and mid-shaft radius., Methods: pQCT was used to measure the 4% and 50% sites of the non-dominant radius in a cohort of healthy white Caucasian children and young adults aged between 5 and 25 years. The lambda, mu, sigma (LMS) technique was used to produce gender-specific reference centile curves and LMS tables for calculating individual standard deviations scores., Results: The study population consisted of 629 participants (380 males). Reference centile curves were produced; total and trabecular BMD for age (distal radius) and for age and height, bone area (distal and mid-shaft radius), cortical area, cortical thickness, BMC, axial moment of inertia, stress-strain index and muscle area (mid-shaft radius)., Conclusions: We present gender-specific databases for the assessment of the distal and mid-shaft radius by pQCT. These data can be used as control data for research studies and allow the clinical interpretation of pQCT measurements in children and young adults by age and height.

Intervertebral discs demonstrate degenerative changes relatively early in life. Disc degeneration, in turn, is associated with back pain and disc herniation, both of which cause considerable clinical problems in the western world. Cell senescence has been linked to degenerative diseases of other connective tissues such as osteoarthritis. Thus we investigated the degree of cell senescence in different regions of discs from patients with different disc disorders. Discs were obtained from 25 patients with disc herniations; from 27 patients undergoing anterior surgery for either back pain due to degenerative disc disease (n = 25) or spondylolisthesis (n = 2) and from six patients with scoliosis. In addition, four discs were obtained post-mortem. Samples were classified as annulus fibrosus or nucleus pulposus and tissue sections were assessed for the degree of cell senescence (using the marker senescence-associated-beta-galactosidase (SA-beta-Gal)) and the number of cells present in clusters. There were significantly more SA-beta-Gal positive cells in herniated discs (8.5% of cells) than those with degenerative disc disease, spondylolisthesis, scoliosis, or cadaveric discs (0.5% of cells; P < 0.001). There was more senescence of cells of the nucleus pulposus compared to those of the annulus fibrosus and in herniated discs a higher proportion of cells in cell clusters (defined as groups of three or more cells) were SA-beta-Gal positive (25.5%) compared to cells not in clusters (4.2%, P < 0.0001). This study demonstrates an increased degree of cell senescence in herniated discs, particularly in the nucleus where cell clusters occur. These clusters have been shown previously to form via cell proliferation, which is likely to explain the increased senescence. These findings could have two important clinical implications: firstly, that since senescent cells are known to behave abnormally in other locations, they may lead to deleterious effects on the disc matrix and so contribute to the pathogenesis and secondly, cells from such tissue may not be ideal for cell therapy and repair via tissue engineering.

Stretching exercise is effective for increasing joint range of motion (ROM). However, the Surgeon General's Report and the American College of Sports Medicine cite a lack of studies identifying strategies capable of increasing the effectiveness of stretching exercise. This investigation evaluated adding modest weight (0.45-1.35 kg) to a stretching exercise routine (Body Recall [BR]) on joint ROM. Forty-three subjects ages 55-83 years participated in 1 of 2 training groups, BR, BR with weights (BR+W), or a control group (C). ROM was evaluated at the neck, shoulder, hip, knee, and ankle before and after 10 weeks of exercise. Using ANCOVA, significant differences (p < 0.01) were observed for right and left cervical rotation, hip extension, ankle dorsiflexion, ankle plantar flexion, and shoulder flexion. Post hoc analysis revealed that cervical rotation (left and right), hip extension, and ankle dorsiflexion for BR+W subjects differed significantly from BR and C (p < 0.01). Significant differences with shoulder flexion and ankle plantar flexion were found for both BR and BR+W in comparison to C (p < 0.01). Results indicate that addition of weights enhanced the effectiveness of stretching exercise for increasing joint ROM with 4 of the 6 selected measurements. Thus, a modest intensity exercise program that is within the reach of most elderly may significantly affect joint ROM and flexibility.

The effect of aging on energy regulation remains controversial. We compared the effects of underfeeding on changes in energy expenditure and respiratory quotient in young normal weight men and women [YNW, age 25.7 +/- 3.2 y(SD), body mass index (BMI) 23.1 +/- 1.6 kg/m(2)], young overweight men and women (YOW, age 26.1 +/- 3.5 y, BMI 27.7 +/- 2.1 kg/m(2)) and older (OLD) men and women (age 68.4 +/- 3.3 y, BMI 27.4 +/- 3.4 kg/m(2)). The thermic effect of feeding (TEF) during weight maintenance, and changes in resting energy expenditure (REE) and respiratory quotient were determined in response to undereating by an average 3.75 MJ/d for 6 wk. In addition, body composition was measured. No significant differences among the groups were observed in TEF, fasting and postprandial respiratory quotient, or the change in fasting respiratory quotient with underfeeding. However, REE adjusted for fat-free mass and fat mass was significantly lower in OLD subjects compared with YNW and YOW subjects (P < 0.05). In addition, the REE response to weight change was significantly attenuated in the OLD subjects (P = 0.023). These data suggest that the responsiveness of energy expenditure to negative energy balance is attenuated in old age, and provide further support for the hypothesis that mechanisms of energy regulation are broadly disregulated in old age.

We investigated the effects of food palatability on the thermic effect of feeding (TEF), substrate oxidation and circulating glucose and insulin. Healthy young men (23.4+/-1.0, SD, years, n=10) and older men (69.4+/-1.3, years, n=9) were resident in a metabolic unit for two 2-day study periods. On the second day of each period, they consumed in random order either a palatable test meal containing 2.93 MJ or a nonpalatable control meal containing the same foods in identical amounts but blended and freeze-dried into biscuit form. TEF and respiratory quotient (RQ) were measured over 6 h and blood samples were taken for measurement of glucose and insulin. Age group had no effect on TEF, RQ or circulating glucose other than to delay the time of peak TEF (P<0.002 for both meals). There was no significant effect of meal type on TEF, but RQ and circulating glucose were higher following consumption of the palatable meal (P<0.001 for both parameters). These results suggest that over 6 h postprandial, consumption of palatable foods does not increase TEF, but is instead associated with increased glycemic response and increased carbohydrate oxidation. These changes, combined with previous work on the glycemic index, predict an accelerated return of hunger and increased energy intake at subsequent meals following consumption of palatable vs. control foods. Further studies are needed to examine the possible mechanism for this previously suggested "second meal" effect of diet palatability on energy intake.

Recent studies have suggested a short-term impairment in the regulation of food intake in older adults, but further studies are needed to determine if a longer-term impairment exists and to identify underlying causes. Changes in body weight and composition were measured over a 6-week underfeeding study and a 6-month follow-up period in healthy young (n = 23) and older (OLD, n = 18) men and women. The young adults were either normal weight (YNW, n = 12) or overweight (YOW, n = 11). Energy intakes during underfeeding were 896 +/- 18 (SEM) kcal less than weight-maintenance energy requirements determined prior to underfeeding. In addition, changes in perceived hunger during underfeeding were monitored in a subgroup (n = 19). OLD and YOW subjects lost significantly more weight during underfeeding than did YNW subjects (p = .025 and .000, respectively), and they did not gain back significant weight in the 6-month follow-up. In addition, OLD subjects reported a significantly lower frequency of hunger during underfeeding (p = .05). There was no significant difference among groups in the relationship between weight lost and fat-free mass lost. Healthy OLD adults have an impaired ability to regulate food intake over at least 6 months following underfeeding compared with YNW adults, and a reduction in their perceived frequency of hunger may be a contributing factor.

Background: Declining resting energy expenditure (REE) is a hallmark of normal aging, but the cause of this decline remains controversial. Some, but not all, studies have shown that the decline in REE with age is eliminated after adjustment for fat-free mass (FFM)., Methods: We examined the effect of four body composition methods used to assess FFM (underwater weighing [UWW], bioimpedance analysis [BIA], tritium dilution, and total body potassium [TBK]) on the relationship between REE and age in 30 healthy men and 101 healthy women aged 18 to 87 years., Results: The decline in REE with age was significant in women (-80.3 kJ/d/y, p < .004) but not in men (-46.9 kJ/d/y, p = .328). After adjustment for FFM, the decline in REE with age persisted when FFM was measured by BIA, UWW, or tritium dilution, but no decline was seen when TBK was used to adjust for FFM. In both women and men, fat mass was significantly associated with REE after adjusting for age and FFM., Conclusion: It is the decline in cell mass with age, detectable by TBK but not by other methods, rather than any metabolic alteration, that explains the decline in FFM-adjusted REE with age.

This review discusses recent studies on possible causes of weight loss in older individuals. Studies of the regulation of food intake suggest that aging is associated with an impairment in the regulation of food intake that inhibits appropriate short-term and long-term compensation for imposed alterations in energy intake. The combination of a reduced ability to regulate energy intake, decreased sensory specific satiety, and adverse social factors such as functional limitations, social isolation and depression, increases the risk of negative energy balance leading to weight loss in older individuals.

Inadequate energy intake can be an important contributor to weight loss in older individuals. This review highlights recent studies on possible causes of negative energy balance in older individuals. Studies of the regulation of food intake suggest that aging is associated with a significant impairment in the regulation of food intake that inhibits appropriate short-term and long-term compensation for imposed alterations in energy intake. The combination of a reduced ability to regulate energy intake, decreased sensory-specific satiety, and disadvantageous social factors such as functional limitations, social isolation and depression, increases the risk of negative energy balance leading to weight loss in older individuals.

Old age is a time of vulnerability to unintentional weight loss, a factor that is associated with increased morbidity and premature death. Many possible causes of weight loss in old age have been suggested. The so-called anorexia of aging may play a particular role, by either reducing food intake directly or reducing food intake in response to such adverse factors as age-associated reductions in taste and smell, poor dentition, use of multiple prescription medicines, and depression. Recent studies also raise the question of whether a reduction in dietary variety may be important. These findings emphasize the need for regular monitoring of body weight to detect unintentional weight loss in older individuals and suggest testable ways to minimize the impact of the anorexia of aging on body weight through improved dietary management.

There remains controversy over the effect of age on postprandial thermogenesis, with some studies observing decreased postprandial thermogenesis in older subjects and other studies finding no effect of age. We investigated this issue in 8 young (25.2+/-1.8 years) and 8 older (72.2+/-2.1 years) healthy glucose-tolerant women with normal thyroid hormone status. Repeated measures of the thermic effect of feeding (TEF) were obtained following consumption of test meals containing 0, 1046, 2092, and 4184 kilojoules (kJ) by using indirect calorimetry. TEF at each meal size was determined once in the older subjects and twice in the younger subjects (during follicular and luteal phases of the menstrual cycle) for a total of 96 measurements. There was a positive dose-response between meal size and TEF (p < .001) that was not significantly affected by age group. The best single predictor of TEF expressed as a percentage of meal energy content was waist-to-hip ratio (R2=67.416, p < .02). These results indicate that aging is not associated with decreased TEF in the absence of factors such as a hypothyroid state or glucose intolerance.

The effects of aging on energy requirements and energy balance have been studied by several research groups using the doubly labeled water method. The weight of evidence from these investigations suggests that current recommended dietary allowances underestimate the usual energy needs of adults of all ages, including older adults. In addition, doubly labeled water studies have found a significant negative association between body fatness and energy expenditure for physical activity, and a significant positive association between energy expenditure for physical activity and fat-free mass. Further studies are needed to refine estimates of energy requirements for different population groups and to address the role of physical activity in the prevention and treatment of obesity.

Ageing is associated with a progressive deterioration in the functions of many organs within the body. In tissue with high cell turnover, the maintenance of the stem cells is of particular importance. Any accumulation of damage in stem cells may affect their function and hence threaten the homeostasis and regenerative capacity of the tissue. The small intestine represents a good model for the study of stem cells because of its spatial and hierarchical organisation. We have examined the effect of age on stem cell regenerative capacity after irradiation, using the microcolony assay. Crypt survival levels, the growth rate of surviving crypts, and the number of cells able to repopulate a crypt have been investigated by irradiating groups of 6-7 month old and 28-30 month old ICRFa male mice. After high doses of irradiation, the surviving crypts in old mice were both smaller and fewer in number than in young mice. The growth rate of surviving crypts was determined by measuring the crypt area and the number of cells/crypt at various times after 14 Gy irradiation. There was a growth delay of between about one half and one day in the older mice. Surprisingly, the number of clonogenic cells per crypt was estimated to be greater in the older mice. These studies indicate important age-related alterations in the capacity to regenerate the crypts after radiation damage.

Blood glucose regulation in the fasting and fed states has important implications for health. In addition, the ability to maintain normal blood glucose homeostasis may be an important determinant of an individual's capacity to regulate food intake. We tested the hypothesis that aging is associated with an impairment in the ability to maintain normal blood glucose homeostasis following the consumption of large meals but not small ones, a factor that could help to explain age-related impairments in the control of food intake and energy regulation. The subjects were eight healthy younger women (25 +/- 2 years, SD) and eight healthy older women (72 +/- 2 years) with normal body weight and glucose tolerance. Following a 36-h period when diet and physical activity were controlled, subjects consumed test meals containing 0, 1046, 2092, and 4184 kJ (simulating extended fasting, and consumption of a snack, a small meal, and a moderately large meal), with 35% of energy from fat, 48% from carbohydrate, and 17% from protein. Each subject consumed each of the test meals on a separate occasion. Serial blood samples were collected at baseline and during 5 h after consumption of the meals. Measurements were made of circulating glucose, insulin, glucagon, free fatty acids, and triglycerides. There was no significant difference between young and older women in their hormone and metabolite responses to fasting and consumption of the 1046-kJ meal. However, following consumption of 2092 and 4148 kJ, older individuals showed exaggerated responses and a delayed return to premeal values for glucose (p = .023), insulin (p = .010), triglycerides (p = .023), and the ratio of insulin to glucagon (p = .026). In conclusion, these results suggest an impairment in the hormonal and metabolite responses to large meals in older women.

The roles of energy expenditure and substrate oxidation in energy regulation, and the effects of factors such as aging on these parameters, remain uncertain. A re-analysis of data from two studies involving overfeeding or underfeeding in young men (22.7 +/- 0.6 [SEM] years) and older men (68.0 +/- 1.50 years) was conducted to further evaluate the adaptive capacity of energy expenditure and respiratory quotient to an increase or a decrease in energy intake. Changes in total energy expenditure (TEE) and resting energy expenditure (REE) and respiratory quotient (RQ) in response to energy imbalance were compared between subjects undergoing overfeeding by 4.1 MJ/day for 21 days, or underfeeding by 3.2 MJ/day for 21 days. Comparing responses to overfeeding or underfeeding, there was a significant TEE response to energy imbalance averaging 1.39 MJ/day and equivalent to 19% of the alteration in energy intake (p < 0.05). There was also a significant REE response to energy imbalance averaging 0.45 MJ/day (p < 0.001), and a significant RQ response in both fasting and fed states (p < 0.01). There was no significant difference between young and older men in their TEE, energy deposition or RQ responses to energy imbalance, but older men did have significantly diminished REE response to energy imbalance (p < 0.05) and a significantly delayed thermic response to a standard meal (p < 0.05). These data indicate that energy expenditure plays a significant role in attenuating the effects of alterations in energy intake on body energy stores and that, based on some measures of energy expenditure, aging is associated with a reduction in the adaptive capacity of energy expenditure to participate in energy regulation.

The accuracy and precision of four different food intake assessment methods were evaluated in young and older women by comparing reported energy intakes with doubly labeled water measurements total energy expenditure (TEE). A study lasting 8 d was conducted in 10 young women aged 25.2+/-1.1 y (-x+/-SEM) and in 10 older women aged 74.0+/-1.4 y. Free-living TEE was measured over 7 d and food consumption was determined from weighed food intake data (7 d), a 24-h food recall (in duplicate), and two different food-frequency questionnaires [Fred Hutchinson Cancer Research Center (FHCRC)/Block and Willett, both in duplicate]. In addition, body composition was determined by using hydrodensitometry, and strenuous physical activity and the extent of dietary restraint were determined by questionnaire. In young women, 24-h recall gave mean energy intakes that were closest to measures of TEE (-0.34+/-3.71 MJ/d compared with TEE, P=0.178), and energy intakes by food-frequency questionnaires were the only intake data that correlated significantly with individual values for TEE (P<0.05). In older women, food-frequency questionnaires gave mean energy intakes that were closest to measured TEE (+0.53+/-2.95 MJ/d with the Willett questionnaire and -1.19+/-3.02 MJ/d with FHCRC/Block questionnaire). No energy intake data from this group correlated significantly with values for TEE. The 7-d weighed dietary intakes were significantly lower than measured TEE in both young and older women (-2.0 MJ/d in young and older women combined, P<0.001), and did not correlate significantly with values for TEE, although they did most closely mirror the mean difference in TEE between the young and older women (2.30 MJ/d for TEE and 2.11 MJ/d for 7-d weighed intake). These data suggest that none of the methods studied gave accurate estimates of the usual energy requirements of individual subjects. In addition, the results suggest that for some types of studies, simple methods for assessing group mean dietary intake may actually give more accurate information than weighed dietary intakes.

Relatively little is known about the influence of age on energy regulation during energy imbalance. We compared the effects of overfeeding on changes in energy expenditure, substrate oxidation, and energy deposition between young men (age 23.7 +/- 1.1 [SEM] years) and older men (age 70.0 +/- 7.0) of normal body weight who were leading unrestricted lives. Changes in total energy expenditure, resting energy expenditure (REE), the thermic effect of feeding (TEF), respiratory quotient (RQ), and body energy content were determined in response to overeating by 4.09 +/- 0.07 Megajoule (MJ)/day for 21 days in 16 healthy subjects consuming a typical diet. After excluding data from one young subject with unusual results and adjusting for individual differences in excess energy intake, there was a tendency towards a smaller increase in REE in older men compared to the young men (p = .07) which was accounted for by their lower fat-free mass (p = .016). There was also a significantly smaller increase in resting energy expenditure averaged over fasting and fed states (i.e, REE + TEF) with overfeeding in older men than in young men (p < .01). Combined, these smaller increases in energy expenditure with overfeeding in the older subjects averaged an estimated 365 kilojoule (kJ)/day (8.9% of the excess energy intake) (p < .02). There were also significant effects of age on fasting RQ (p < .001) and the change in RQ with overfeeding (p < .001), but no significant increase in energy expenditure for physical activity and thermoregulation with overfeeding in either age-group. These results are consistent with the suggestion that older individuals experience both a reduction in the ability to increase energy expenditure, and an alteration in the pattern of substrate utilization, in response to overfeeding. These changes may promote cumulative increases in body energy during normal cycles of positive energy balance unless compensated for by adaptive variations in energy intake.

Relatively little is known about the influence of age on energy regulation during energy imbalance. We compared the effects of underfeeding on changes in energy expenditure, substrate oxidation, and body energy loss between young men (age 22.0 +/- 0.9 [SEM] years) and older men (age 66.0 +/- 1.8) who were leading unrestricted lives. Changes in total energy expenditure (TEE), resting energy expenditure (REE), the thermic effect of feeding (TEF), respiratory quotient, and body energy loss were determined in response to undereating by 3.17 +/- 0.16 Megajoule (MJ)/day for 21 days in 19 healthy subjects consuming a typical diet. No significant effects of age were observed in changes in TEE, REE, TEF, or body energy loss in response to underfeeding. Thus, older men do not appear to have any impairment of energy conservation during negative energy balance compared to young men. This normal pattern of energy conservation during undereating together with the previously demonstrated reduction in energy dissipation during overeating can be predicted to promote body fat deposition in older men during the cycles of positive and negative energy balance that occur during normal life. This finding may help to explain the increased body fat mass in older individuals.

The effects of aging on energy requirements and energy expenditure were investigated in 35 healthy young men (mean +/- SE age, 22.7 +/- 0.6 y) and elderly men (68.0 +/- 1.5 y). Over a 10-d metabolic balance study, measurements were made of metabolizable energy intake for weight maintenance, total energy expenditure, resting energy expenditure, and thermic effect of feeding. Values for both metabolizable energy intake and total energy expenditure were significantly higher than the current recommended dietary allowance for energy in both age groups (P < 0.01). Total energy expenditures were 14.48 +/- 0.65 and 11.26 +/- 5.40 MJ/d in young and elderly men, respectively. The difference in total energy expenditure between the groups was accounted for by a significant decrease in all the major components of expenditure. These results suggest that the current recommended dietary allowances for energy may underestimate the usual energy needs of healthy adult men.

Inadequate energy intake can be an important contributor to sarcopenia in older individuals, because negative energy balance induces negative nitrogen balance, independent of nitrogen intake. This review highlights recent studies from our laboratory on possible causes of negative energy balance in older individuals. Studies of energy requirements determined by measurement of total energy expenditure during weight maintenance, using the doubly labeled water technique, and the control of food intake following overeating and undereating indicate (a) that older individuals have higher energy requirements than anticipated, based on current Recommended Dietary Allowances for energy, and (b) that aging is associated with a significant impairment in the control of food intake, which inhibits appropriate compensation for prior changes in energy intake. The combination of unexpectedly high energy needs, and an inability to accurately control energy intake, increases the risk for negative energy balance and associated body fat and protein losses in older individuals.

The intervertebral discs undergo profound changes in structure and composition during development and aging. They also degenerate much earlier than other cartilaginous tissues, and in severe cases may lose function completely. The reasons for this early degeneration are unknown, but external factors, such as mechanical overload on the spine, or smoking, may be involved. However, recent work has revived interest in the importance of genetic and developmental influences on the intervertebral discs.

There is little information on the effects of age on energy requirements in women. This issue was investigated in a cross-sectional study of 10 normal-weight young women aged 25.2 +/- 1.1 y (mean +/- SEM) and 10 normal-weight older women aged 74.0 +/- 1.4 y. In a 9-d study, measurements were made of free-living total energy expenditure (TEE) by using the doubly labeled water technique, body composition by using hydrodensitometry, and resting energy expenditure (REE) by using indirect calorimetry. Mean values for reported levels of strenuous activity were within the expected range in both groups (31 +/- 13 min/d in the young group and 7 +/- 2 min/d in the older group). Energy requirements expressed as the ratio of TEE to REE were 1.80 +/- 0.10 and 1.62 +/- 0.06 (P < 0.01) in the young and older group, respectively. When values for REE predicted from body weight (pREE) were used, as suggested in the current recommended dietary allowances (RDAs), the ratios of TEE to pREE in the two groups were 1.85 +/- 0.10 and 1.54 +/- 0.04 (P < 0.05). The RDAs significantly under-predicted the energy requirements of the young group (P < 0.05), but there was no significant underprediction in the older group. Although obtained in a relatively small number of subjects, these results provide no evidence to indicate that the current RDAs underestimate the energy requirements of older women, in contrast with previous observations of an underestimation of energy requirements by the RDAs in older men.

Objective: To investigate the effects of aging on mechanisms of body energy regulation and thereby determine the causes of unexplained weight loss in older persons, a factor predisposing to premature death and disability., Design: Dietary intervention study., Setting: Metabolic ward and outpatient., Participants: The subjects were 35 healthy younger and older men of normal body weight consuming a diet of typical composition and performing usual activities., Main Outcome Measures: Subjects were either overfed by a mean (+/- SD) of 4.09 (+/- 0.26) MJ/d (n = 17) or underfed by 3.17 (+/- 0.68) MJ/d (n = 18) for 21 days. Measurements were made of changes in body weight, body composition, and energy expenditure during overfeeding or underfeeding, and of subsequent voluntary nutrient intakes and changes in body weight., Results: There was no significant effect of aging on changes in body composition, body weight, or energy expenditure with overfeeding or underfeeding. However, following overfeeding, younger men exhibited spontaneous hypophagia, whereas the older men did not (mean [+/- SD] changes in energy intake relative to control values were -2.11 [+/- 2.18] and 1.55 [+/- 2.11] MJ/d, respectively; P = .006). As a result, the younger men lost the excess body weight gained during overfeeding but the older men did not. Similarly, following underfeeding, the younger men exhibited hyperphagia while the older men did not (mean [+/- SD] changes in energy intake relative to control values were 1.88 [+/- 2.31] and -0.52 [+/- 1.54] MJ/d, respectively; P = .02), and as a result the older men failed to regain the weight lost during underfeeding., Conclusions: These results in 35 men suggest that aging may be associated with a significant impairment in the ability to control food intake following overeating or undereating. Since overeating and undereating occur routinely as part of the normal pattern of energy regulation, the findings reported herein may help to explain the vulnerability of older persons to unexplained weight gain and weight loss.

Monoclonal antibodies have been used to study the presence and distribution of various components of the proteoglycan molecule in the intervertebral disc and cartilage endplate. Link protein, hyaluronic acid binding region, keratan sulphate and chondroitin 4- and 6-sulphate have been investigated in tissues from humans and other mammals. Exposure of the carbohydrate and protein epitopes was enhanced by chondroitinase and trypsin pretreatment respectively. The degree of immunoreactivity varied with location, being greater in the nucleus pulposus than the annulus fibrosus with least reactivity in the cartilage endplate. In addition, there was increased staining in the pericellular domains, particularly in adult tissues. Areas of ectopic calcification exhibited very different immunoreactivity, depending on the type of calcium salt present. Calcium hydroxyapatite deposits showed greater staining for 8A4 (link protein), while calcium pyrophosphate deposits demonstrated greater staining for 3B3(-), 7D4(-) and 3D5 than the surrounding non-calcified matrix. Staining for chondroitin sulphate isomer epitopes 3B3(-) and 7D4(-), indicative of modified chondroitin sulphate chains, was greater in human tissues of degenerate than non-degenerate appearance. This suggests that expression of these epitopes may be an indicator of disease and subsequent reparative procedures in intervertebral disc and cartilage endplate, similar to that seen in articular cartilage degeneration.

We investigated the importance of adaptive variations in energy expenditure in the regulation of energy balance in young and elderly men of normal body weight leading unrestricted lives. Changes were measured in total and resting energy expenditure and body composition in response to overeating by approximately 4.2 MJ/d or undereating by 3.3 MJ/d for 21 d in 39 young and elderly men consuming a typical diet. In the young men, an average of 85-90% of the excess energy intake during overeating was deposited. During underfeeding, mobilization of body energy compensated for an average of 65% of the energy deficit in these subjects. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (+0.63 +/- 0.20 MJ/d, P < 0.01) and decreased during underfeeding (-0.42 +/- 0.12 MJ/d), but at least some of these changes were due to the obligatory expenditure associated with nutrient assimilation. There was no significant change in energy expenditure for physical activity or thermoregulation from overfeeding or underfeeding. Preliminary results indicate that aging had no effect on responses to overfeeding or underfeeding. These findings suggest that adaptive variations in energy expenditure are not the major determinant of energy regulation in young adults of normal body weight and that, instead, energy balance is maintained on a day-to-day basis through the control of nutrient intakes.

The energy requirements of healthy elderly men were investigated by measuring total energy expenditure (TEE), body composition and resting energy expenditure (REE), using 2H2(18)O techniques and indirect calorimetry during ten days when a weight maintaining diet was consumed. Values for TEE/REE (1.75 +/- 0.05, s.e.) were significantly higher than the recommended dietary allowances (RDAs) for energy in this age group, as were previously reported values for TEE/REE in a group of young men in the same experimental protocol. There was a significant negative association between TEE/REE (a physical activity indicator) and body fat mass. Combining data from the elderly men in this study and the young men studied previously, age and TEE/REE together accounted for 73% of the variation in body fat mass between individuals. These results lend additional weight to the suggestion that the current RDAs for energy may significantly under-estimate usual energy requirements. They also indicate that the low levels of energy expenditure suggested by the RDAs may favour unnecessarily high levels of body fat mass and that increased levels of energy expenditure are desirable.

Although emigration from the former Soviet Union is dramatically increasing nationwide, little information has been reported on the medical problems of these emigrés. For older emigrés in particular, the medical realities of aging, in combination with cultural expectations, make the United States' medical system an arena where the stresses of emigration are expressed and help is sought. We describe the influences of culture and aging on older emigrés' health and interaction with the American medical system. A qualitative, exploratory study was done of problems and issues in health care use by older Russian emigrés at the ambulatory medical clinic of Mount Zion Medical Center, San Francisco. Cultural expectations and beliefs about health, adaptive health behaviors learned in the former Soviet Union, the stresses of emigration, and the medical realities of aging can result in serious problems in the care and treatment of older Russian emigrés. Recommended solutions include educating emigrés and health care professionals, integrating mental health services into the primary care setting, and expanding supportive services in the community such as adult day health care.

Age-related changes in serum levels of somatomedin-like growth factors were measured using a bioassay based on myoblast proliferation in culture. The correspondence of this assay to thymidine incorporation and sulfation factor assays for somatomedins was demonstrated. Comparisons involved individual serum samples from a total of 28 rats at each of three age ranges (young = 2 to 6 month, middle-aged = 12 to 16 month, and old = 24 to 28 month) in five separate experiments. A small (10%) decrease in levels of somatomedin-like activity was observed between young and middle-aged animals, with a greater (20 to 40%) subsequent decrease in old rats. Assays of mixed samples indicated that the age-related decreases in somatomedin-like activity could not be attributed to increases in circulating levels of a dissociable inhibitor of this activity. Paired comparisons of amino acid uptake by isolated omohyoideus muscles from rats of the specified ages suggested that there were no significant age-related changes in response of these muscles to a somatomedin analog.

The clinical pharmacokinetics of enteric-coated sulphasalazine (Salazopyrin-EN) were studied after acute and chronic dosing in 20 patients with 'active' rheumatoid arthritis. 12 elderly (mean age 74.4 +/- 1 yr; range 71-83) and 8 young (mean age 40.5 +/- 1.4 yr; range 35-46) patients were given a single 2 g oral dose of sulphasalazine after an overnight fast. Serum and urine samples were collected at regular intervals over a 96 hour period for estimation of concentrations of sulphasalazine, sulphapyridine and its metabolites. This procedure was repeated after 17 days of continuous treatment with salazopyrin-EN 2 g daily in order to compare the drug's kinetics at 'steady-state'. Whilst the interindividual variation in kinetic parameters was large, age and acetylator status had a significant influence on a number of factors. The elimination half-life of sulphasalazine was prolonged in the elderly whilst renal clearance was increased in slow acetylators at 'steady-state'. The tmax and apparent volume of distribution of sulphapyridine were increased in the elderly after a single drug dosage but these differences disappeared with regular dosing. The Cmax, elimination half-life, 'steady-state' serum concentration, apparent volume of distribution and total clearance of sulphapyridine were all affected by acetylator status. We conclude that old age has only a minor effect on the body's handling of sulphasalazine and sulphapyridine but that acetylator phenotype plays a significant role in determining the 'steady-state' serum concentrations of sulphapyridine. This is likely to have practical implications with regard to some of the drug's adverse effects.

Digital health is transforming the delivery of health care around the world to meet the growing challenges presented by ageing populations with multiple chronic conditions. Digital health technologies can support the delivery of personalised nutrition care through the standardised Nutrition Care Process (NCP) by using personal data and technology‐supported delivery modalities. The digital disruption of traditional dietetic services is occurring worldwide, supporting responsive and high‐quality nutrition care. These disruptive technologies include integrated electronic and personal health records, mobile apps, wearables, artificial intelligence and machine learning, conversation agents, chatbots, and social robots. Here, we outline how digital health is disrupting the traditional model of nutrition care delivery and outline the potential for dietitians to not only embrace digital disruption, but also take ownership in shaping it, aiming to enhance patient care. An overview is provided of digital health concepts and disruptive technologies according to the four steps in the NCP: nutrition assessment, diagnosis, intervention, and monitoring and evaluation. It is imperative that dietitians stay abreast of these technological developments and be the leaders of the disruption, not simply subject to it. By doing so, dietitians now, as well as in the future, will maximise their impact and continue to champion evidence‐based nutrition practice. [ABSTRACT FROM AUTHOR]

We conducted a randomised exploratory trial in children aged between one and sixteen years old to establish the time to achieve an end-tidal oxygen fraction ≥ 0.9 in three different positions: supine, and 30 and 45° head up. We recruited 120 children analysed in two age groups: 1-8 years and 9-16 years. The median (IQR [range]) time to reach the end point was 80 (59-114 [41-295]) s in the younger group and 150 (107-211 [44-405]) s in the older group, regardless of position (p = 0.0001). The end point was reached in 90% of children in approximately 160 s in the younger, and 271 s in the older, groups, respectively. There was no statistical difference between the three positions within each age group in the time to reach the endpoint (p = 0.59). Only two patients in the older age group could not reach the end point, due to poorly fitting facemasks. We conclude that pre-oxygenation can therefore be achieved effectively in most children, and that tilting children head up by 30 or 45° does not significantly reduce the time taken to achieve an end-tidal oxygen fraction of ≥ 0.9. The recommended period for pre-oxygenation in both groups should remain at 3 min but it should be noted that this may be insufficient for many older patients. [ABSTRACT FROM AUTHOR]

The term frailty describes an age-related state of vulnerable health. The aetiology of this condition is not well understood. A number of mechanisms may contribute to frailty. Amongst these is the possible influence of age-related perturbations of sex hormones, particularly, the fall in testosterone in ageing men. This declining androgenic function has been thought to contribute to the loss of muscle mass (sarcopaenia) and strength that occurs with ageing and thereby underpin the development of frailty. Testosterone replacement has therefore been suggested as a possible intervention to treat frailty. This review summarizes evidence from observational and interventional studies on the effects of testosterone on frailty and its key components including body composition, muscle strength and physical function. Evidence from these studies is considered against study design, methodological issues and in the context of the current understanding of frailty. The role of androgens in the development of frailty and their utility in treating this condition are evaluated. Future research directions for the use of androgens in the treatment of frailty are suggested. The potential interaction between testosterone and other frailty mechanisms and the possibility that secondary components of the sex hormone system may be appropriate frailty biomarkers are also discussed. [ABSTRACT FROM AUTHOR]

This article examines the rationale for a four-week life experience placement for nursing students developed at the school of community and health sciences at London's City University. The authors describe how students' perceptions of old age have been challenged by listening to someone's life history and observing older people in groups and in the community. Student Daniel Fitzpatrick reflects on his experience of undertaking the placement in relation to his own feelings and expectations of old age. [ABSTRACT FROM AUTHOR]

The intervertebral disc is reported to age faster than other connective tissues with significant degenerative changes already seen in the second decade of life. In other tissues, senescent cells have an altered phenotype, often with a decreased synthetic ability and response to anabolic cytokines. They appear to contribute to age-related pathologies such as the degeneration of articular cartilage in osteoarthritis. Little is known of cell senescence in the intervertebral disc. In this study, we have investigated the production of senescence-associated-ß-galactosidase (SA-ß-Gal), a ‘biomarker’ of cell senescence, in intervertebral disc cells both in cultured populations in vitro, and in vivo, in pathological human discs. Intervertebral disc cells were extracted from coccygeal bovine discs and cultured for 3 months. Confluent cell preparations were stained for SA-β-Gal ( ) at passages 0, 1, 2, 3 and 4. Preparations were fixed in 3% paraformaldehyde in phosphate-buffered saline (PBS) for 5 min at room temperature and incubated for 24 h at 37 °C in SA-ß-Gal solution containing 1 mg/ml 5-bromo-4-chloro-3-indolyl ß- d-galactopyranoside (X-Gal, Sigma, Poole, UK), 5 mmol/l potassium ferrocyanide, 5 mmol/l potassium ferricyanide, 150 mmol/l NaCl, 2 mmol/l MgCl2 and 40 mmol/l trisodium citrate, titrated with NaH2PO4 to pH 6.0. Lysosomal (nonsenescent) ß-galactosidase activity was detected using the same solution but titrated to pH 4.0. After staining, preparations were rinsed in ice-cold PBS, dehydrated and mounted. Pathological human disc from patients with disc herniations or discogenic back pain were also stained for SA-β-Gal (immersing the tissue in the stain solution overnight) then cryosectioning (10 µm thick) and fixing. Articular cartilage was studied for comparison ( ). Cultured intervertebral discs demonstrated some staining for SA-ß-Gal at all passages investigated, but there was little change in staining with passage number. Cells in most pathological human discs demonstrated staining for SA-ß-Gal. Positive cells were seen more commonly in herniated discs [7/9 (78%); mean age: 46 ± 13] than in those removed from patients with discogenic back pain [2/6 (33%); mean age: 32 ± 5]. To our knowledge, this is the first study of cell senescence in intervertebral disc cells. The greatest level was seen in tissue from herniated discs where cell cluster formation and cell proliferation are common (but the mean age of the herniation group was slightly higher than the discogenic back pain group). However, for a tissue demonstrating such significant age-related degenerative changes, there is surprisingly little expression of SA-ß-Gal in comparison with that found in other pathological cartilages. These preliminary data suggest that, unlike the situation in osteoarthritis, early cell senescence is not a major contributing factor in the pathogenesis of disc degeneration. [ABSTRACT FROM AUTHOR]

Abstract: The Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study is a systematic investigation of sustained 25% calorie restriction (CR) in non-obese humans. CALERIE is a multicenter (3 clinical sites, one coordinating center), parallel group, randomized controlled trial. Participants were recruited, screened, and randomized to the CR or control group with a 2:1 allocation. Inclusion criteria included ages 21–50years for men and 21–47years for women, and a body mass index (BMI) of 22.0≤BMI<28.0kg/m2. Exclusion criteria included abnormal laboratory markers, significant medical conditions, psychiatric/behavioral problems, and an inability to adhere to the rigors of the evaluation/intervention schedule. A multi-stage screening process (telephone screen and 3 in-clinic visits) was applied to identify eligible participants. Recruitment was effective and enrollment targets were met on time. 10,856 individuals contacted the clinical sites, of whom 9787 (90%) failed one or more eligibility criteria. Of the 1069 volunteers who started the in-clinic screening, 831 (78%) were either ineligible or dropped. 238 volunteers were enrolled (i.e., initiated the baseline evaluations), 220 were randomized, and 218 started the assigned intervention (2% from the first screening step). This study offered lessons for future multi-center trials engaging non-disease populations. Recruitment strategies must be tailored to specific sites. A multi-disciplinary screening process should be applied to address medical, physical, and psychological/behavioral suitability of participants. Finally, a multi-step screening process with simple criteria first, followed by more elaborate procedures has the potential to reduce the use of study resources. [Copyright &y& Elsevier]