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Macronutrients in Frailty and Aging

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Geriatric Nutrition".

Deadline for manuscript submissions: closed (30 October 2022) | Viewed by 30667

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Special Issue Editors

Dr. Sarah J. Mitchell

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Guest Editor

Department of Health Sciences and Technology, ETH Zürich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland
Interests: ageing; longevity; healthspan; dietary restriction; calorie restriction; pharmacological interventions; rodents; nutrition

Dr. Michael R. MacArthur

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Guest Editor

Department of Health Sciences and Technology, ETH Zürich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland
Interests: amino acids; nutrient signaling; protein restriction; obesity; metabolic disease; computational biology

Special Issue Information

Dear Colleagues,

As we advance our understanding of the role of nutrition in health, we have come to recognize the important part that macronutrients play in ageing and disease processes. Restriction of total energy and certain macronutrients have shown beneficial effects on longevity, but many critical questions remain on the role of diet in ageing beyond just lifespan. For example, what is the role of diet in promoting healthspan and reducing frailty? Are the geroprotective effects of certain diets sexually dimorphic? What are the optimal dietary strategies to promote healthy longevity?

The intent of this Special Issue is to highlight the important role of diet in ageing and frailty, with a focus on macronutrients. Preclinical or human original research, reviews or meta-analyses focusing on macronutrients and some aspect of healthy ageing, diseases of ageing or frailty are particularly welcome for this Special Issue.

In light of your expertise in this subject area, you are invited to submit original research (including short communications of preliminary but significant results), reviews (narrative or systematic), or meta-analyses for this Special Issue of Nutrients focused on the role of ‘Macronutrients in Frailty, Heath and Disease’.

Dr. Sarah J. Mitchell
Dr. Michael R. MacArthur
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

macronutrients
health
longevity
disease
frailty
protein
carbohydrate
fat
micronutrients
dietary interventions
nutritional interventions
translation
preclinical models
clinical studies/models
age-related diseases
ageing
obesity
metabolism

Published Papers (9 papers)

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Research

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18 pages, 1734 KiB

Open AccessArticle

Long-Term Calorie Restriction Alters Anxiety-like Behaviour and the Brain and Adrenal Gland Transcriptomes of the Ageing Male Rat

by Antonina Govic, Helen Nasser, Elizabeth A. Levay, Matt Zelko, Esmaeil Ebrahimie, Manijeh Mohammadi Dehcheshmeh, Stephen Kent, Jim Penman and Agnes Hazi

Nutrients 2022, 14(21), 4670; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14214670 - 04 Nov 2022

Cited by 9 | Viewed by 2099

Abstract

Further examination of the molecular regulators of long-term calorie restriction (CR), reported to have an anxiolytic effect, may highlight novel therapeutic targets for anxiety disorders. Here, adult male Hooded Wistar rats were exposed to a 25% CR whilst anxiety-like behaviour was assessed at 6-, 12-, and 18-months of age via the elevated plus maze, open field, and acoustic startle tests. Next-generation sequencing was then used to measure transcriptome-wide gene expression in the hypothalamus, amygdala, pituitary, and adrenal glands. Results showed an anxiolytic behavioural profile across early, middle, and late adulthood by CR, with the strongest effects noted at 6-months. Transcriptomic analysis by seven attribute weighting algorithms, including Info Gain Ratio, Rule, Chi Squared, Gini Index, Uncertainty, Relief, and Info Gain, led to the development of a signature of long-term CR, independent of region. Complement C1q A chain (C1qa), an extracellular protein, expression was significantly decreased by CR in most regions examined. Furthermore, text mining highlighted the positive involvement of C1qa in anxiety, depression, neurodegeneration, stress, and ageing, collectively identifying a suitable biomarker candidate for CR. Overall, the current study identified anxiety-related phenotypic changes and a novel transcriptome signature of long-term CR, indicating potential therapeutic targets for anxiety, depression, and neurodegeneration. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

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19 pages, 3713 KiB

Open AccessFeature PaperArticle

Temporal Dynamics of the Intestinal Microbiome Following Short-Term Dietary Restriction

by Erik M. Anderson, Jared M. Rozowsky, Brian J. Fazzone, Emilie A. Schmidt, Bruce R. Stevens, Kerri A. O’Malley, Salvatore T. Scali and Scott A. Berceli

Nutrients 2022, 14(14), 2785; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14142785 - 06 Jul 2022

Cited by 5 | Viewed by 3058

Abstract

Short-term dietary restriction has been proposed as an intriguing pre-operative conditioning strategy designed to attenuate the surgical stress response and improve outcomes. However, it is unclear how this nutritional intervention influences the microbiome, which is known to modulate the systemic condition. Healthy individuals were recruited to participate in a four-day, 70% protein-restricted, 30% calorie-restricted diet, and stool samples were collected at baseline, after the restricted diet, and after resuming normal food intake. Taxonomy and functional pathway analysis was performed via shotgun metagenomic sequencing, prevalence filtering, and differential abundance analysis. High prevalence species were altered by the dietary intervention but quickly returned to baseline after restarting a regular diet. Composition and functional changes after the restricted diet included the decreased relative abundance of commensal bacteria and a catabolic phenotype. Notable species changes included Faecalibacterium prausnitzii and Roseburia intestinalis, which are major butyrate producers within the colon and are characteristically decreased in many disease states. The macronutrient components of the diet might have influenced these changes. We conclude that short-term dietary restriction modulates the ecology of the gut microbiome, with this modulation being characterized by a relative dysbiosis. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

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10 pages, 643 KiB

Open AccessArticle

Therapeutic Fasting: Are Patients Aged 65 and Over Ready?

by Baptiste Gramont, Martin Killian, Elodie Bernard, Laure Martinez, Sebastien Bruel, Bogdan Galusca, Nathalie Barth and Thomas Célarier

Nutrients 2022, 14(10), 2001; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14102001 - 10 May 2022

Viewed by 1816

Abstract

While being the main potential beneficiaries of therapeutic fasting’s health benefits, the elderly are frequently thought of as being too fragile to fast. The main objective of our survey was to review the knowledge, practices, and acceptability of therapeutic fasting in subjects aged 65 years and over. From September 2020 to March 2021, an online questionnaire was sent to subjects aged 65 and over, using the mailing list of local organizations working in the field of aging. The mean age of the 290 respondents was 73.8 ± 6.5 years, 75.2% were women and 54.1% had higher education. Among the respondents, 51.7% had already fasted and 80.7% deemed therapeutic fasting interesting, 83.1% would be willing to fast if it was proven beneficial for their health, and 77.2% if it was proven to decrease the burden of chronic diseases. Subjects aged 65 to 74 years considered themselves as having the greatest physical and motivational abilities to perform therapeutic fasting. People aged 65 years, or more, are interested in therapeutic fasting and a large majority would be ready to fast if such practice was proven beneficial. These results pave the way for future clinical trials evaluating therapeutic fasting in elderly subjects. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

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19 pages, 2991 KiB

Open AccessArticle

Sulfur Amino Acid Supplementation Abrogates Protective Effects of Caloric Restriction for Enhancing Bone Marrow Regrowth Following Ionizing Radiation

by Christopher Hine, J. Humberto Treviño-Villarreal, Pedro Mejia, Alban Longchamp, Lear E. Brace, Eylul Harputlugil, Sarah J. Mitchell, Jie Yang, Yihong Guan, Jaroslaw P. Maciejewski, Babal K. Jha and James R. Mitchell

Nutrients 2022, 14(7), 1529; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14071529 - 06 Apr 2022

Cited by 1 | Viewed by 2857

Abstract

Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance. Here, we report that 50% calorie restriction (CR) for 7-days or fasting for 3-days prior to irradiation improved mouse BM regrowth in the days and weeks post irradiation. Specifically, one week of 50% CR ameliorated loss of total BM cellularity post irradiation compared to ad libitum-fed controls. CR-mediated BM protection was abrogated by dietary sulfur amino acid (i.e., cysteine, methionine) supplementation or pharmacological inhibition of sulfur amino acid metabolizing and hydrogen sulfide (H₂S) producing enzymes. Up to 2-fold increased proliferative capacity of ex vivo-irradiated BM isolated from food restricted mice relative to control mice indicates cell autonomy of the protective effect. Pretreatment with H₂S in vitro was sufficient to preserve proliferative capacity by over 50% compared to non-treated cells in ex vivo-irradiated BM and BM HSPCs. The exogenous addition of H₂S inhibited Ten eleven translocation 2 (TET2) activity in vitro, thus providing a potential mechanism of action. Short-term CR or fasting therefore offers BM radioprotection and promotes regrowth in part via altered sulfur amino acid metabolism and H₂S generation, with translational implications for radiation treatment and aging. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

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15 pages, 1233 KiB

Open AccessArticle

Guava Fruit and Acacia pennata Vegetable Intake Association with Frailty of Older Adults in Northern Thailand

by Jetsada Ruangsuriya, Rawiwan Wongpoomchai, Somdet Srichairatanakool, Wachiranun Sirikul, Nida Buawangpong and Penprapa Siviroj

Nutrients 2022, 14(6), 1192; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14061192 - 11 Mar 2022

Cited by 1 | Viewed by 2848

Abstract

As Thailand moves toward an aging society, frailty has become a concern amongst northern Thai elderly. The causes of frailty are multifactorial and include genetic, environmental, and socio-economic factors; diet is of particular interest. A cross-sectional study was conducted from September to October 2017 to investigate what kind of diets normally consumed by 350 Thai elders were associated with frailty using a questionnaire and frailty determination by Fried’s phenotype followed by phytochemical analyses of the diets. The multivariable logistic regression analysis demonstrated a significant positive association between certain foods and lower frailty. Guava fruit and Acacia pennata vegetable consumption had lower odds of frailty, which were 0.52 times (95% CI 0.28–0.96, p = 0.037) and 0.42 times (95% CI 0.21–0.83, p = 0.012) when adjusted for the potential confounders. The phytochemical analyses of guava fruit showed a significantly higher amount of total flavonoids (p < 0.001), total phenolic compounds (p = 0.002), and antioxidant capacity, including DPPH (p < 0.001), ABTS (p < 0.001), and FRAP (p = 0.002) when compared to those of banana. Acacia pennata vegetable contained a significantly higher amount of total phenolic compounds (p = 0.012) when compared to those of lettuce. These findings may assist in health promotion programs of frailty prevention by encouraging an increase in consumption of either guava fruit or Acacia pennata vegetable among Thai elderly. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

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13 pages, 303 KiB

Open AccessArticle

A Comparison of Dietary Intake and Nutritional Status between Aged Care Residents Consuming Texture-Modified Diets with and without Oral Nutritional Supplements

by Xiaojing Sharon Wu, Lina Yousif, Anna Miles and Andrea Braakhuis

Nutrients 2022, 14(3), 669; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14030669 - 05 Feb 2022

Cited by 4 | Viewed by 3011

Abstract

Oral nutritional supplements (ONS) are high-energy and protein-rich nutrition drinks that are commonly prescribed to individuals with compromised nutritional status. Aged care residents requiring texture-modified diets are exposed to poor oral intake and malnutrition. This study aimed to investigate the dietary intake and nutritional status of residents consuming texture-modified diets with and without ONS. This multicentre cross-sectional study included 85 residents consuming texture-modified diets (86.0 ± 8.7 y; n = 46 requiring ONS and n = 39 without ONS). A one-day dietary record was completed using a validated visual plate waste estimation method. To determine the adequacy, nutrition intake was then calculated using FoodWorks (Xyris Ltd., Brisbane, Australia) and compared to the recommended dietary intake for Australia and New Zealand. The Mini-Nutritional Assessment Short Form was collected to assess nutritional status. Residents receiving ONS had significantly higher energy, protein, carbohydrates and fat intake than those who did not consume ONS (p < 0.05). No significant differences were found in saturated fat, fibre or sodium intake. With the administration of ONS, residents were able to meet their protein requirement but fell short of their energy and carbohydrates requirements. Both groups had inadequate fibre intake and a high saturated fat intake. A total of 48% of the residents were at risk of malnutrition and 38% were malnourished. Aged care residents requiring texture-modified diets are at high risk of malnutrition as a result of inadequate dietary intake. Administration of ONS may be an effective strategy to optimise nutrition intake. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

17 pages, 2208 KiB

Open AccessArticle

Short-Term Pre-Operative Protein Caloric Restriction in Elective Vascular Surgery Patients: A Randomized Clinical Trial

by Peter Kip, Thijs J. Sluiter, Jodene K. Moore, Abby Hart, Jack Ruske, James O’Leary, Jonathan Jung, Ming Tao, Michael R. MacArthur, Patrick Heindel, Alwin de Jong, Margreet R. de Vries, M. Furkan Burak, Sarah J. Mitchell, James R. Mitchell and C. Keith Ozaki

Nutrients 2021, 13(11), 4024; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13114024 - 11 Nov 2021

Cited by 5 | Viewed by 2985

Abstract

(1) Background: Vascular surgery operations are hampered by high failure rates and frequent occurrence of peri-operative cardiovascular complications. In pre-clinical studies, pre-operative restriction of proteins and/or calories (PCR) has been shown to limit ischemia-reperfusion damage, slow intimal hyperplasia, and improve metabolic fitness. However, whether these dietary regimens are feasible and safe in the vascular surgery patient population remains unknown. (2) Methods: We performed a randomized controlled trial in patients scheduled for any elective open vascular procedure. Participants were randomized in a 3:2 ratio to either four days of outpatient pre-operative PCR (30% calorie, 70% protein restriction) or their regular ad-libitum diet. Blood was drawn at baseline, pre-operative, and post-operative day 1 timepoints. A leukocyte subset flow cytometry panel was performed at these timepoints. Subcutaneous/perivascular adipose tissue was sampled and analyzed. Follow-up was one year post-op. (3) Results: 19 patients were enrolled, of whom 11 completed the study. No diet-related reasons for non-completion were reported, and there was no intervention group crossover. The PCR diet induced weight loss and BMI decrease without malnutrition. Insulin sensitivity was improved after four days of PCR (p = 0.05). Between diet groups, there were similar rates of re-intervention, wound infection, and cardiovascular complications. Leukocyte populations were maintained after four days of PCR. (4) Conclusions: Pre-operative PCR is safe and feasible in elective vascular surgery patients. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

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16 pages, 5073 KiB

Open AccessArticle

Gut Microbiota Predicts Healthy Late-Life Aging in Male Mice

by Shanlin Ke, Sarah J. Mitchell, Michael R. MacArthur, Alice E. Kane, David A. Sinclair, Emily M. Venable, Katia S. Chadaideh, Rachel N. Carmody, Francine Grodstein, James R. Mitchell and Yang-Yu Liu

Nutrients 2021, 13(9), 3290; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13093290 - 21 Sep 2021

Cited by 10 | Viewed by 6647

Abstract

Calorie restriction (CR) extends lifespan and retards age-related chronic diseases in most species. There is growing evidence that the gut microbiota has a pivotal role in host health and age-related pathological conditions. Yet, it is still unclear how CR and the gut microbiota are related to healthy aging. Here, we report findings from a small longitudinal study of male C57BL/6 mice maintained on either ad libitum or mild (15%) CR diets from 21 months of age and tracked until natural death. We demonstrate that CR results in a significantly reduced rate of increase in the frailty index (FI), a well-established indicator of aging. We observed significant alterations in diversity, as well as compositional patterns of the mouse gut microbiota during the aging process. Interrogating the FI-related microbial features using machine learning techniques, we show that gut microbial signatures from 21-month-old mice can predict the healthy aging of 30-month-old mice with reasonable accuracy. This study deepens our understanding of the links between CR, gut microbiota, and frailty in the aging process of mice. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

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Review

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21 pages, 940 KiB

Open AccessReview

The Use of Dietary Supplements and Amino Acid Restriction Interventions to Reduce Frailty in Pre-Clinical Models

by Elise S. Bisset and Susan E. Howlett

Nutrients 2022, 14(14), 2806; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14142806 - 08 Jul 2022

Viewed by 4089

Abstract

Frailty is a state of accelerated aging that increases susceptibility to adverse health outcomes. Due to its high societal and personal costs, there is growing interest in discovering beneficial interventions to attenuate frailty. Many of these interventions involve the use of lifestyle modifications such as dietary supplements. Testing these interventions in pre-clinical models can facilitate our understanding of their impact on underlying mechanisms of frailty. We conducted a narrative review of studies that investigated the impact of dietary modifications on measures of frailty or overall health in rodent models. These interventions include vitamin supplements, dietary supplements, or amino acid restriction diets. We found that vitamins, amino acid restriction diets, and dietary supplements can have beneficial effects on frailty and other measures of overall health in rodent models. Mechanistic studies show that these effects are mediated by modifying one or more mechanisms underlying frailty, in particular effects on chronic inflammation. However, many interventions do not measure frailty directly and most do not investigate effects in both sexes, which limits their applicability. Examining dietary interventions in animal models allows for detailed investigation of underlying mechanisms involved in their beneficial effects. This may lead to more successful, translatable interventions to attenuate frailty. Full article

(This article belongs to the Special Issue Macronutrients in Frailty and Aging)

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