ResearchPad - Gerontology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Sarcopenia and Variation in the Human Leukocyte Antigen Complex]]> https://www.researchpad.co/product?articleinfo=Nee65c444-2060-400f-b6aa-db2b22613ce8

Abstract

Background

Aging is characterized by chronic inflammation plus loss of muscle mass and strength, termed sarcopenia. Human leukocyte antigen (HLA) types are drivers of autoimmune disease, although with limited penetrance. We tested whether autoimmune diagnoses are associated with sarcopenia, and whether HLA types and related genetic variants are associated with sarcopenia in autoimmune disease-free older people.

Methods

Data were collected from 181,301 UK Biobank European descent volunteers aged 60–70 with measured hand grip strength and impedance. Logistic regression analysis estimated HLA type and sarcopenia associations, adjusted for confounders and multiple testing.

Results

Having any autoimmune diagnosis was associated with sarcopenia (odds ratio [OR] 1.83, 95% confidence interval (CI) 1.74–1.92, p = 4.0*10−125). After excluding autoimmune diagnoses, 6 of 100 HLA types (allele frequency >1%) were associated with sarcopenia (low grip strength and muscle mass). Having two HLA-DQA1*03:01 alleles increased odds of sarcopenia by 19.3% (OR 1.19, CI 1.09–1.29, p = 2.84*10–5), compared to no alleles. Having ≥6 of the 12 HLA alleles increased sarcopenia odds by 23% (OR 1.23, CI 1.12–1.35, p = 7.28*10–6). Of 658 HLA region non-coding genetic variants previously implicated in disease, 4 were associated with sarcopenia, including rs41268896 and rs29268645 (OR 1.08, CI 1.05–1.11, p = 1.06*10–8 and 1.07, CI 1.04–1.09, p = 1.5*10–6, respectively). Some HLA associations with sarcopenia were greater in female participants.

Conclusion

Autoimmune diagnoses are strongly associated with sarcopenia in 60- to 70-year olds. Variation in specific HLA types and non-coding single nucleotide polymorphisms is also associated with sarcopenia in older carriers free of diagnosed autoimmune diseases. Patients with sarcopenia might benefit from targeted treatment of autoimmune processes.

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<![CDATA[Candidate Biomarkers of Aging: Age-Sensitive Indices of Immune and Muscle Function Covary in Genetically Heterogeneous Mice]]> https://www.researchpad.co/product?articleinfo=N6f75c468-380b-49bb-a9bc-23f68f20881c

Abstract

A longitudinal experiment was designed to test the hypothesis that individual mice differ in their aging rate and to validate candidate biomarkers proposed to measure the rate of aging. Mice were bred as the genetically heterogeneous progeny of a cross between CB6F1 mothers and C3D2F1 fathers. Half of the mice were fed ad libitum (AL group), and the other half were subjected to 60% calorie restriction (CR group). Each mouse was tested at about 9 months of age using age-sensitive tests of immune status, and then again at about 12 months of age using age-sensitive tests of muscle function. The data were then analyzed using the method of partial least squares to determine the combinations of test weights that maximize the covariance of the weighted sum of immune measures with the weighted sum of muscle function measures. Both AL and CR mice exhibited a statistically significant relation between the immune status tests and the muscle function tests. Maximal covariance was obtained with a set of weighting coefficients consistent with our working hypothesis: mice with high levels of CD4 memory T cells (which increase with age) also had relatively low levels of muscle strength and endurance. Low strength was associated with low CD8 cells in the AL mice, with high numbers of CD8 memory cells in the CR mice and with low CD3 cells in both diet groups. The partial least squares method generates composite indices of immune status and muscle function that can be evaluated as biomarkers of aging rate in these mice. Further work will be needed to assess whether these tests predict either longevity or the trajectory of change in other age-sensitive molecular and physiological traits.

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<![CDATA[Food Restriction Differentially Affects mRNAs Encoding the Major Anterior Pituitary Tropic Hormones]]> https://www.researchpad.co/product?articleinfo=N4b83c9d1-e085-4f88-b7e3-2035dc1a41e4

Abstract

Chronic food restriction (FR) leads to adaptive cellular changes, some of which retard aging. Moreover, some of these changes occur within weeks after onset of FR. Because neuroendocrine mechanisms may mediate these effects, we measured the effect of FR on the messenger ribonucleicacids (mRNAs) encoding all of the tropic hormones of the anterior pituitary (AP). Slot blot and solution hybridization were conducted on AP ribonucleicacid (RNA) samples obtained at 0500 h (AM) and 1500 h (PM) from 3-month-old male Fischer 344 rats fed ad libitum (AL) or FR (60% of AL calories) since 6 weeks of age. Poly A RNA/μg total RNA was similar in AL and FR rats, indicating that there was no overall effect of FR on mRNA levels. The level of proopiomelanocortin (POMC) mRNA was not reduced by FR when expressed per fig of RNA or as total AP content. By contrast, the total AP content of the mRNAs encoding LHβ, FSHβ TSHβ, GH, and PRL was markedly reduced by FR. When expressed per fig of RNA, however, only GH (AM and PM), FSHβ (AM), TSHbeta; (PM), and PRL (PM) were reduced by FR. These results reveal that FR differentially affects pituitary tropic hormone mRNA levels within weeks after onset of FR, and are consistent with a role for neuroendocrine alterations in the initiation of adaptive cellular responses to FR.

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<![CDATA[Pathologic Characterization of Brown Norway, Brown Norway × Fischer 344, and Fischer 344 × Brown Norway Rats With Relation to Age]]> https://www.researchpad.co/product?articleinfo=Na03304bf-4662-4dc2-99f0-ed31cb029687

Abstract

The rat is a common laboratory animal utilized in a variety of investigations including experimental gerontology. Gerontologic investigations can be compromised when the differences observed when comparing young and old animals are actually differences between normal and disease states. It is of critical interest to know the pathology of the animals being studied and to understand the impact of these disease processes on the parameters being measured. The incidence and average age of occurrence for lesions have been characterized and are reported here for one inbred (Brown Norway) and two hybrid strains (Brown Norway × Fischer 344 and Fischer 344 × Brown Norway) of rat. Total lesion incidence functions as a biomarker of aging for all of the strains examined (p ≤ .00001). These three genotypes have significantly lower incidence of several major pathologic processes (including glomerulonephritis, retinal atrophy, and leukemia) than do the Fischer 344 and the Wistar rats, two commonly utilized strains. Additionally, the BN and F344 × BN F1 hybrid attain 50% mortality at 130 and 146 weeks of age, respectively, which is significantly greater than the 103 weeks for the F344 rat. It is hoped that access to basic information on these three rat genotypes will increase their utilization by the community of gerontologic scientists.

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<![CDATA[Genetic Loci That Influence Cause of Death in a Heterogeneous Mouse Stock]]> https://www.researchpad.co/product?articleinfo=Na83b5d78-7797-4eda-9c26-aa8baee6d533

Abstract

A genome scan was conducted to seek evidence for polymorphic genes that influence cause of death in mice produced by a cross between CB6F1 females and C3D2F1 males. Loci on chromosomes 1 and 4 were found to modulate risk of lymphoma. A locus on chromosome 4 influenced risk of mammary adenocarcinoma among multiparous female mice, but had no significant effect in virgin females. A chromosome 4 locus was found to modulate risk of death from either hemangiosarcoma or fibrosarcoma. A suggestive linkage was noted (at p =.09) between a marker on chromosome 11 and hepatocellular carcinoma. Lastly, a locus on chromosome 6 was noted to influence the likelihood that pulmonary adenocarcinoma would be present at death. The collection of normal and neoplastic tissues from 1004 terminal necropsies, together with genetic information, provides a valuable resource for further studies of the genetic influences on late-life diseases in mice.

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<![CDATA[Previous Hepatitis A Virus Infection Is Related to Slower Psychomotor Speed in Elderly Adults]]> https://www.researchpad.co/product?articleinfo=N3ed142e4-2b1e-46fd-9e48-f10f5588e07f

Abstract

Background

Patients with chronic viral hepatitis are at a higher risk for cognitive dysfunction. Little is known about the association between hepatitis A virus (HAV) infection and cognitive function.

Methods

From the National Health and Nutrition Examination Survey, 1999–2002, we selected study participants (≥60 years, n = 1,529) without hepatitis B, C, or D virus infection; without previous hepatitis A vaccination; and without abnormal liver function. HAV-seropositive participants represented people with previous HAV infection. Psychomotor speed and executive functioning domain of cognitive function were measured by the Digit Symbol Substitution Test (DSST).

Results

HAV-seropositive participants had lower DSST scores than HAV-seronegative participants (weighted mean, 44.4 vs 53.9, p < .001). We designated HAV-seronegative participants as the reference group. Univariate analysis demonstrated that the weighted β coefficient of DSST score was −9.55 (95% confidence interval [CI] −9.57 to −9.54, p < .001) for the HAV-seropositive participants. In a multivariable model, the weighted adjusted β coefficient of DSST score was −2.48 (95% CI −2.49 to −2.46, p < .001) for the HAV-seropositive participants.

Conclusion

HAV seropositivity is associated with slower psychomotor speed among the U.S. community-dwelling elders.

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<![CDATA[Principles of Animal Use for Gerontological Research]]> https://www.researchpad.co/product?articleinfo=N7c4aa198-fe6c-40f8-95bf-bd05ca7dbdf7

Abstract

This essay presents some practical advice and suggestions for those who wish to use mice and rats in experiments on the biology of aging. Ten principles set forth guidance on choice of ages, choice of stocks, the importance of specific pathogen–free status, the uses of necropsy data, the dangers of pooling samples from different individuals, planning ahead for loss of aged mice to death and disease, the use of cost-adjusted power calculations, and the dangers of inferring causal associations from correlated age effects.

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<![CDATA[Relationship Between Aging and Renal High-Affinity Sodium-Dependent Dicarboxylate Cotransporter-3 Expression Characterized With Antifusion Protein Antibody]]> https://www.researchpad.co/product?articleinfo=N05c4e480-97fc-478b-afdb-3d41fed4422a

Abstract

Sodium-dependent dicarboxylate cotransporter (NaDC), which is responsible for the transportation of intermediates of the Krebs cycle, has been implicated in extending the life span of drosophila. In the present study, we cloned an intracellular domain segment of human kidney NaDC-3, which is 75% identical to that of the rat, constructed a polyclonal antibody against fusion protein of glutathione S-transferase (GST)-NaDC-3, and detected its renal expression changes with aging in both Wistar rats and normal humans. Western blot and immunohistochemistry confirmed the specificity of the antibody, and its location was found to be on the basolateral membrane of the renal proximal tubule. In addition, Western and Northern blots showed that NaDC-3 in kidneys significantly increased with age in Wistar rats. In healthy humans, renal NaDC-3 abundance also increased with age. Our results demonstrated that NaDC-3 expression was increased in aged Wistar rats and aged people, indicating that NaDC-3 may have a role in the process of kidney aging.

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<![CDATA[Social Isolation and Memory Decline in Later-life]]> https://www.researchpad.co/product?articleinfo=N84d16c33-57dc-4351-927b-c27e24dc6ee4

Abstract

Objectives

To investigate associations between level and changes in social isolation and in memory in older men and women.

Methods

The sample included 6,123 women and 5,110 men aged 50+ from the English Longitudinal Study of Aging (ELSA). Extended latent change score models from six measurement occasions every 2 years from 2002 were used to investigate associations between social isolation and memory. Models were adjusted for age, socioeconomic position, and health.

Results

Social isolation increased and memory decreased over time. Among men an initially high level of social isolation was associated with a somewhat greater decrease in memory. Among women a greater increase in social isolation predicted a greater decrease in memory and a larger change in social isolation was associated with further larger changes in isolation, although when social isolation reached a higher level it subsequently decreased.

Conclusions

Results suggest that the association between social isolation and memory decline arises because social isolation is associated with increased memory decline rather than poor memory leading to increases in social isolation. Men with high levels of social isolation and women with accumulated social isolation over time are especially affected as these patterns of isolation were associated with more profound memory decline.

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<![CDATA[Geriatric Health Charts for Individual Assessment and Prediction of Care Needs: A Population-Based Prospective Study]]> https://www.researchpad.co/product?articleinfo=N0f9345e5-770c-4843-b693-734afbc202e8

Abstract

Background

Geriatric health charts that are similar to pediatric growth charts could facilitate monitoring health changes and predicting care needs in older adults. We aimed to validate an existing composite score (Health Assessment Tool [HAT]) and provide provisional age-specific reference curves for the general older population.

Methods

Data came from the Swedish National study on Aging and Care in Kungsholmen (N = 3,363 participants aged 60 years and over examined clinically at baseline and 3 years later). HAT was validated by exploring its relationship with health indicators (logistic regression) and comparing its ability to predict care consumption with that of two of its components, morbidity and disability (receiver operating characteristic curve areas). A flowchart was developed to obtain individual-level HAT scores (nominal response method). Sex-specific health charts were derived by graphing seven percentile curves of age-related HAT change (logistic quantile regression).

Results

HAT scores above the age- and sex-specific median were related to good performance in chair-stand tests (odds ratio [OR] = 2.62, 95% confidence interval [CI]: 2.07–3.31), balance and grip tests (interaction balance grip test, OR = 1.15, 95% CI: 1.05–1.25), and good self-rated health (OR = 2.19, 95% CI: 1.77–2.71). Receiver operating characteristic curve areas (HAT vs number of chronic disorders) were formal care, 0.76 versus 0.58 (p value < .001); informal care, 0.74 versus 0.59 (p value < .001); hospital admission, 0.70 versus 0.66 (p value < .001); primary care visits, 0.71 versus 0.69 (p value > .05); and specialty care visits, 0.62 versus 0.65 (p value < .001). HAT consistently predicted medical and social care service use better than disability.

Conclusions

HAT is a valid tool that predicts care consumption well and could be useful in developing geriatric health charts to better monitor health changes in older populations.

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<![CDATA[Age and Gender Differences in Social Network Composition and Social Support Among Older Rural South Africans: Findings From the HAALSI Study]]> https://www.researchpad.co/product?articleinfo=N6024b835-113c-4d32-b5f8-7fa4a5971143

Abstract

Objectives

Drawing on the “Health and Aging in Africa: A Longitudinal Study of an INDEPTH community in South Africa” (HAALSI) baseline survey, we present data on older adults’ social networks and receipt of social support in rural South Africa. We examine how age and gender differences in social network characteristics matched with patterns predicted by theories of choice- and constraint-based network contraction in older adults.

Method

We used regression analysis on data for 5,059 South African adults aged 40 and older.

Results

Older respondents reported fewer important social contacts and less frequent communication than their middle-aged peers, largely due to fewer nonkin connections. Network size difference between older and younger respondents was greater for women than for men. These gender and age differences were explicable by much higher levels of widowhood among older women compared to younger women and older men. There was no evidence for employment-related network contraction or selective retention of emotionally supportive ties.

Discussion

Marriage-related structural constraints impacted on older women’s social networks in rural South Africa, but did not explain choice-based network contraction. These findings suggest that many older women in rural Africa, a growing population, may have an unmet need for social support.

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<![CDATA[Loneliness, Social Integration, and Incident Dementia Over 6 Years: Prospective Findings From the English Longitudinal Study of Ageing]]> https://www.researchpad.co/product?articleinfo=Nbf862093-47a8-4b95-acba-1356f25bbc70

Abstract

Objectives

Social relationships are important for the maintenance of cognitive function at older ages, with both objective features of social networks and perceived social connections (loneliness) being relevant. There is limited evidence about how different aspects of social experience predict diagnosed dementia.

Methods

The sample comprised 6,677 dementia-free individuals at baseline (2004) from the English Longitudinal Study of Ageing. Baseline information on loneliness, number of close relationships, marital status, and social isolation (contact with family and friends and participation in organizations) was analyzed in relation to incident dementia over an average 6.25 years using Cox regression, controlling for potential confounding factors.

Results

Two hundred twenty participants developed dementia during follow-up. In multivariable analyses, dementia risk was positively related to greater loneliness (hazard ratio 1.40, 95% confidence interval 1.09–1.80, p = .008), and inversely associated with number of close relationships (p < .001) and being married (p = .018). Sensitivity analyses testing for reverse causality and different criteria for diagnosing dementia confirmed the robustness of these findings. There was no association with social isolation.

Discussion

Dementia risk is associated with loneliness and having fewer close relationships in later life. The underlying mechanisms remain to be elucidated, but efforts to enhance older peoples’ relationship quality may be relevant to dementia risk.

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<![CDATA[Testing Comparability Between Retrospective Life History Data and Prospective Birth Cohort Study Data]]> https://www.researchpad.co/product?articleinfo=Nad9ca345-68ab-4a60-a264-855e857b26cb

Abstract

Objectives

To determine whether comparable prospective and retrospective data present the same association between childhood and life course exposures and mid-life wellbeing.

Method

Prospective data is taken from the 1958 UK National Child Development Study at age 50 in 2008 and earlier sweeps (n = 8,033). Retrospective data is taken from the English Longitudinal Study of Ageing at ages 50–55 from a life history interview in 2007 (n = 921).

Results

There is a high degree of similarity in the direction of association between childhood exposures that have been prospectively collected in National Child Development Study and retrospectively collected in English Longitudinal Study of Ageing and wellbeing outcomes in mid-life. However, the magnitude of these associations is attenuated substantially by the inclusion of measurements, which are difficult or impossible to capture retrospectively, and are only available in prospective data, such as childhood poverty, cognitive ability, and indices of social and emotional adjustment.

Discussion

The findings on the one hand provide some reassurance to the growing literature using life history data to determine life course associations with later life wellbeing. On the other hand, the findings show an overestimation in the retrospective data, in part, arising from the absence in life history data of childhood measures that are not well suited to retrospective collection.

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<![CDATA[Gender Differences in the Association Between Leisure Activity in Adulthood and Cognitive Function in Old Age: A Prospective Longitudinal Population-Based Study]]> https://www.researchpad.co/product?articleinfo=N37c1208b-8c27-4be8-b6b6-015a12bdd00d

Abstract

Objectives

To examine the long-term association between leisure activities in adulthood and cognitive function in old age while recognizing gender differences in activity profiles.

Methods

The sample included 340 cognitively healthy twins enrolled in the OCTO-Twin Study, a longitudinal study on cognitive aging. Leisure activity was measured in midlife and cognitive function in old age (mean age 83). Leisure activities covered the domains of domestic, intellectual–cultural, and self-improvement activities. The cognitive assessments comprised 5 measurement occasions (2-year intervals) covering verbal ability, spatial ability, memory, and speed. The association between leisure activity and cognitive function was estimated separately for the genders using growth curve models, adjusting for age and education.

Results

Men and women had the same level of total leisure activity but differed in activity profiles and in the associations between activity and cognitive function. Higher engagement in self-improvement among men was related to higher level of cognitive functioning. Among women, intellectual–cultural activity was related to better verbal ability and memory. Concerning trajectories of cognitive function, domestic activity among men was related to less decline in speed, whereas for women it was related to steeper decline in spatial ability and memory. Further, higher intellectual–cultural activity among women was related to steeper decline in memory.

Discussion

Cognitively stimulating activities (i.e., self-improvement and intellectual–cultural), might increase cognitive reserve whereas less cognitively stimulating activities (i.e., domestic) do not. Gender differences should be considered when examining lifestyle factors in relation to cognitive aging.

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<![CDATA[Living Longer, With or Without Disability? A Global and Longitudinal Perspective]]> https://www.researchpad.co/product?articleinfo=Nc40c0d00-a0f3-4e81-a6bf-3ae5b129d87d

Abstract

Background

Significant gains in life expectancy have been achieved, but living longer does not necessarily mean the years gained are productive and healthy. Different theories predict different patterns of time trends in old-age disability prevalence.

Methods

Using the Gateway to Global Aging Data, which provides internationally harmonized longitudinal data from the Health and Retirement Study and its sister surveys, we compare time trends (from 2004 to 2014) in disability prevalence across countries.

Results

Disability prevalence varies greatly across countries, and divergent time trends are observed across countries. For countries such as Belgium, Czechia, and Mexico, we observe an increase of disability prevalence, whereas in countries such as Denmark, England, Greece, Korea, Poland, and Sweden, we observe a substantial decrease in disability prevalence. Looking further into the severity of disability, we often observe differential trends in prevalence, but there is no evidence supporting the dynamic equilibrium hypothesis that predicts increased prevalence of modest disability but a decrease in severe disability prevalence.

Conclusions

Significant gains in life expectancy have translated into different gains in healthy years of life across different countries. Diverse time trends in disability prevalence across countries reaffirm that the expansion of late-life disability is not inevitable.

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<![CDATA[The Prevalence of Orthostatic Hypotension: A Systematic Review and Meta-Analysis]]> https://www.researchpad.co/product?articleinfo=Nddca2a3c-3d1c-4e8b-8a63-a4b3d19b8e4a

Abstract

Background

Orthostatic hypotension (OH) is associated with increased risk of falls, cognitive impairment and death, as well as a reduced quality of life. Although it is presumed to be common in older people, estimates of its prevalence vary widely. This study aims to address this by pooling the results of epidemiological studies.

Methods

MEDLINE, EMBASE, PubMed, Web of Science, and ProQuest were searched. Studies were included if participants were more than 60 years, were set within the community or within long-term care and diagnosis was based on a postural drop in systolic blood pressure (BP) ≥20 mmHg or diastolic BP ≥10 mmHg. Data were extracted independently by two reviewers. Random and quality effects models were used for pooled analysis.

Results

Of 23,090 identified records, 20 studies were included for community-dwelling older people (n = 24,967) and six were included for older people in long-term settings (n = 2,694). There was substantial variation in methods used to identify OH with differing supine rest duration, frequency and timing of standing BP, measurement device, use of standing and tilt-tables and interpretation of the diagnostic drop in BP. The pooled prevalence of OH in community-dwelling older people was 22.2% (95% CI = 17, 28) and 23.9% (95% CI = 18.2, 30.1) in long-term settings. There was significant heterogeneity in both pooled results (I2 > 90%).

Conclusions

OH is very common, affecting one in five community-dwelling older people and almost one in four older people in long-term care. There is great variability in methods used to identify OH.

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<![CDATA[Protein Intake and Functional Integrity in Aging: The Framingham Heart Study Offspring]]> https://www.researchpad.co/product?articleinfo=Nacad2205-9355-4837-a940-c5bff4e3e97c

Abstract

Background

Higher protein intake is linked to maintenance of muscle mass and strength, but few studies have related protein to physical function and disability in aging.

Methods

In participants of the Framingham Heart Study Offspring, we examined associations between protein intake (g/d), estimated from food frequency questionnaires, and maintenance of functional integrity, as a functional integrity score based on responses to 17 questions from Katz Activities of Daily Living, Nagi, and Rosow-Breslau questionnaires, repeated up to five times (1991/1995–2011/2014) over 23 years of follow-up. Cox proportional hazard models were used to estimate risk of incident loss of functional integrity (functional integrity score ≤ 15th percentile).

Results

In 2,917 participants (age 54.5 [9.8] years), baseline protein intake was 77.2 (15.6) g/d. The functional integrity score (baseline, mean 98.9, range 82.4–100.0) was associated with objective performance (gait speed, grip strength) and lower odds of falls, fractures, and frailty. Across follow-up, there were 731 incident cases of loss of functional integrity. In fully adjusted models, participants in the highest category of protein intake (median 92.2 g/d) had 30% lower risk of loss of functional integrity (hazard ratio [95% confidence interval] 0.70 [0.52, 0.95], p trend = .03), versus those with the lowest intake (median 64.4 g/d). However, sex-stratified analyses indicated the association was driven by the association in women alone (hazard ratio [95% confidence interval] 0.49 [0.32, 0.74], p trend = .002) and was nonsignificant in men (hazard ratio [95% confidence interval] 1.14 [0.70, 1.86], p trend = .59).

Conclusions

Higher protein intake was beneficially associated with maintenance of physical function in middle-aged, high-functioning U.S. adults over the span of two decades. This association was particularly evident in women.

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<![CDATA[Is Rapamycin a Dietary Restriction Mimetic?]]> https://www.researchpad.co/product?articleinfo=Ncd7026d0-5c27-4bbc-bf6d-cba65bae5d67

Abstract

Since the initial suggestion that rapamycin, an inhibitor of target of rapamycin (TOR) nutrient signaling, increased lifespan comparable to dietary restriction, investigators have viewed rapamycin as a potential dietary restriction mimetic. Both dietary restriction and rapamycin increase lifespan across a wide range of evolutionarily diverse species (including yeast, Caenorhabditis elegans, Drosophila, and mice) as well as reducing pathology and improving physiological functions that decline with age in mice. The purpose of this article is to review the research comparing the effect of dietary restriction and rapamycin in mice. The current data show that dietary restriction and rapamycin have different effects on many pathways and molecular processes. In addition, these interventions affect the lifespan of many genetically manipulated mouse models differently. In other words, while dietary restriction and rapamycin may have similar effects on some pathways and processes; overall, they affect many pathways/processes quite differently. Therefore, rapamycin is likely not a true dietary restriction mimetic. Rather dietary restriction and rapamycin appear to be increasing lifespan and retarding aging largely through different mechanisms/pathways, suggesting that a combination of dietary restriction and rapamycin will have a greater effect on lifespan than either manipulation alone.

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<![CDATA[Metabolic Effects of Breaking Prolonged Sitting With Standing or Light Walking in Older South Asians and White Europeans: A Randomized Acute Study]]> https://www.researchpad.co/product?articleinfo=Ncc66ad76-4d42-4791-b3fc-9aa3bedc1d18

Abstract

Background

Prolonged sitting is common in older adults and is associated with insulin resistance and poor cardiometabolic health. We investigate whether breaking prolonged sitting with regular short bouts of standing or light walking improves postprandial metabolism in older white European and South Asian adults and whether effects are modified by ethnic group.

Methods

Thirty South Asian (15 women) and 30 white European (14 women) older adults (aged 65–79 years) undertook three experimental conditions in random order. (a) Prolonged sitting: continuous sitting during an observation period if 7.5 hours consuming two standardized mixed meals. (b) Standing breaks: sitting interrupted with 5 minutes of standing every 30 minutes (accumulating 60 minutes of standing over the observation period). (c) Walking breaks: sitting interrupted with 5 minutes of self-paced light walking every 30 minutes (accumulating 60 minutes of walking). Blood samples (glucose, insulin, triglycerides) and blood pressure were sampled regularly throughout each condition.

Results

Compared with prolonged sitting, walking breaks lowered postprandial insulin by 16.3 mU/L, (95% CI: 19.7, 22.0) with greater reductions (p = .029) seen in South Asians (22.4 mU/L; 12.4, 32.4) than white Europeans (10.3 mU/L; 5.9, 14.7). Glucose (0.3 mmol/L; 0.1, 0.5) and blood pressure (4 mm Hg; 2, 6), but not triglycerides, were lower with walking breaks, with no ethnic differences. Standing breaks did not improve any outcome.

Conclusions

Breaking prolonged sitting with short bouts of light walking, but not standing, resulted in clinically meaningful improvements in markers of metabolic health in older adults, with South Asians gaining a greater reduction in postprandial insulin.

Trial Registration

NCT02453204

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<![CDATA[Branched-Chain Amino Acids Have Equivalent Effects to Other Essential Amino Acids on Lifespan and Aging-Related Traits in Drosophila]]> https://www.researchpad.co/product?articleinfo=Na097743c-e6f0-455f-9718-d64fc261f915

Abstract

Branched-chain amino acids (BCAAs) have been suggested to be particularly potent activators of Target of Rapamycin (TOR) signaling. Moreover, increased circulating BCAAs are associated with higher risk of insulin resistance and diabetes in both mice and humans, and with increased mortality in mice. However, it remains unknown if BCAAs play a more prominent role in longevity than do other essential amino acids (EAAs). To test for a more prominent role of BCAAs in lifespan and related traits in Drosophila, we restricted either BCAAs or a control group of three other EAAs, threonine, histidine and lysine (THK). BCAA restriction induced compensatory feeding, lipid accumulation, stress resistance and amelioration of age-related gut pathology. It also extended lifespan in a dietary-nitrogen-dependent manner. Importantly, the control restriction of THK had similar effects on these phenotypes. Our control diet was designed to have every EAA equally limiting for growth and reproduction, and our findings therefore suggest that the level of the most limiting EAAs in the diet, rather than the specific EAAs that are limiting, determines the response of these phenotypes to EAA restriction.

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