bims-minfam 2021-11-28 papers

bims-minfam

Biomed News

on Inflammation and metabolism in ageing and cancer

Issue of 2021–11–28
27 papers selected by
Ayesh Seneviratne, University of Toronto

Clonal hematopoiesis and VEXAS syndrome: survival of the fittest clones?
The Role of Immune Cells in Oxi-Inflamm-Aging.
The Roles of RNA N6-Methyladenosine in Regulating Stem Cell Fate.
Cancer Stem Cells: Metabolic Characterization for Targeted Cancer Therapy.
Nutrition senolytics - illusion or reality for cognitive ageing?
A US State Index of Successful Aging: Differences Between States and Over Time.
New Directions in Research on Aging.
Negative Perception of Aging Is Associated With Frailty Transitions Within a Cohort of Sexual Minority Men.
Anti-aging effects of the fermented anthocyanin extracts of purple sweet potato on Caenorhabditis elegans.
Effects of Nutrition on Cognitive Function in Adults with or without Cognitive Impairment: A Systematic Review of Randomized Controlled Clinical Trials.
Number of ideas in spontaneous speech predicts cognitive impairment and frailty in community-dwelling older adults nine years later.
How record wildfires are harming human health.
The effect of smiling on the perceived age of male and female faces across the lifespan.
Hospital Frailty Risk Score Is Independently Associated with Mortality and Encephalopathy in Hospitalized Patients with Hepatocellular Carcinoma.
Adherence to the Mediterranean diet assessed by a novel dietary biomarker score and mortality in older adults: the InCHIANTI cohort study.
Geriatric Oncology: From Research to Clinical Practice.
Clinician knowledge and behaviors related to the 4Ms framework of Age-Friendly Health Systems.
Comparison of Antiobesity Effects of Adipose-Derived Stromal/Stem Cells from Different Sources in a Natural Aging Model.
Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions.
Cardiotoxicity of Antineoplastic Therapies and Applications of Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Role of Deep Learning in Predicting Aging-Related Diseases: A Scoping Review.
A 4-pronged approach to foster healthy aging in older adults.
Immune ageing at single-cell resolution.
Development of a new clinical index to easily assess frailty of elderly patients with multiple myeloma in Asian population.
Metformin treatment of diverse Caenorhabditis species reveals the importance of genetic background in longevity and healthspan extension outcomes.
Shortage of aspartate in mitochondria fuels arthritis.
Pathophysiology of Vascular Calcification and Bone Loss: Linked Disorders of Ageing?

Semin Hematol. 2021 Oct;pii: S0037-1963(21)00050-0. [Epub ahead of print]58(4): 226-229

Clonal hematopoiesis and VEXAS syndrome: survival of the fittest clones?

Yael Kusne, Jenna Fernandez, Mrinal M Patnaik.

  Clonal hematopoiesis (CH) is defined by the acquisition of somatic mutations in hematopoietic stem cells (HSC) leading to enhanced cellular fitness and proliferation under positive clonal selection pressures. CH most frequently involves epigenetic regulator genes (DNMT3A, TET2 and ASXL1), with these mutations being associated with enhanced inflammation and increased all-cause mortality largely from cardiovascular disease and endothelial dysfunction. These mutations also increase the risk for hematological neoplasms. Somatic mutations in UBA1, encoding the E1 ubiquitin ligase in HSC, cause a severe adult-onset autoinflammatory disease that can be associated with myeloid and plasma cell neoplasms, termed VEXAS (vacuoles, X-linked, autoinflammatory, somatic) syndrome. Given the degree of inflammation seen, one would have expected this to be a fertile ground for CH development and propagation, however, preliminary data doesn't support this. Here in, we review the current data on CH, inflammation and VEXAS syndrome.

Keywords:  Clonal hematopoiesis; Inflammation; Somatic mutations; UBA1

DOI:  https://doi.org/10.1053/j.seminhematol.2021.10.004
Cells. 2021 Nov 01. pii: 2974. [Epub ahead of print]10(11):

The Role of Immune Cells in Oxi-Inflamm-Aging.

Irene Martínez de Toda, Noemi Ceprián, Estefanía Díaz-Del Cerro, Mónica De la Fuente.

  Aging is the result of the deterioration of the homeostatic systems (nervous, endocrine, and immune systems), which preserve the organism's health. We propose that the age-related impairment of these systems is due to the establishment of a chronic oxidative stress situation that leads to low-grade chronic inflammation throughout the immune system's activity. It is known that the immune system weakens with age, which increases morbidity and mortality. In this context, we describe how the function of immune cells can be used as an indicator of the rate of aging of an individual. In addition to this passive role as a marker, we describe how the immune system can work as a driver of aging by amplifying the oxidative-inflammatory stress associated with aging (oxi-inflamm-aging) and inducing senescence in far tissue cells. Further supporting our theory, we discuss how certain lifestyle conditions (such as social environment, nutrition, or exercise) can have an impact on longevity by affecting the oxidative and inflammatory state of immune cells, regulating immunosenescence and its contribution to oxi-inflamm-aging.

Keywords:  aging; biological age; immune cells; inflammatory stress; oxidative stress

DOI:  https://doi.org/10.3390/cells10112974
Front Cell Dev Biol. 2021 ;9 765635

The Roles of RNA N6-Methyladenosine in Regulating Stem Cell Fate.

Runbi Ji, Xu Zhang.

  RNA N6-methyladenosine (m6A) modification has important regulatory roles in determining cell fate. The reversible methylation process of adding and removing m6A marks is dynamically regulated by a fine-tuned coordination of many enzymes and binding proteins. Stem cells have self-renewal and pluripotent potential and show broad prospects in regenerative medicine and other fields. Stem cells have also been identified in cancer, which is linked to cancer metastasis, therapy resistance, and recurrence. Herein, we aimed to review the molecular mechanism that controls the reversible balance of m6A level in stem cells and the effect of m6A modification on the balance between pluripotency and differentiation. Additionally, we also elaborated the association between aberrant m6A modification and the maintenance of cancer stem cells in many cancers. Moreover, we discussed about the clinical implications of m6A modification in cancer stem cells for cancer diagnosis and therapy.

Keywords:  N6-methyladenosine; cancer; cell differentiation; post-transcriptional modifications; stem cell

DOI:  https://doi.org/10.3389/fcell.2021.765635
Front Oncol. 2021 ;11 756888

Cancer Stem Cells: Metabolic Characterization for Targeted Cancer Therapy.

Jasmeet Kaur, Shalmoli Bhattacharyya.

  The subpopulation of cancer stem cells (CSCs) within tumor bulk are known for tumor recurrence and metastasis. CSCs show intrinsic resistance to conventional therapies and phenotypic plasticity within the tumor, which make these a difficult target for conventional therapies. CSCs have different metabolic phenotypes based on their needs as compared to the bulk cancer cells. CSCs show metabolic plasticity and constantly alter their metabolic state between glycolysis and oxidative metabolism (OXPHOS) to adapt to scarcity of nutrients and therapeutic stress. The metabolic characteristics of CSCs are distinct compared to non-CSCs and thus provide an opportunity to devise more effective strategies to target CSCs. Mechanism for metabolic switch in CSCs is still unravelled, however existing evidence suggests that tumor microenvironment affects the metabolic phenotype of cancer cells. Understanding CSCs metabolism may help in discovering new and effective clinical targets to prevent cancer relapse and metastasis. This review summarises the current knowledge of CSCs metabolism and highlights the potential targeted treatment strategies.

Keywords:  OxPhos; cancer stem cell; glucose; glutamine; metabolism

DOI:  https://doi.org/10.3389/fonc.2021.756888
Curr Opin Clin Nutr Metab Care. 2021 Nov 22.

Nutrition senolytics - illusion or reality for cognitive ageing?

Xi Chen, Henry Brodaty, Fiona O'Leary.

PURPOSE OF REVIEW: Cell senescence is implicated in numerous age-related conditions. Antiageing therapies and nutritional approaches have been researched for purposes of removing senescent cells (senolytics) to treat or prevent age-related diseases, such as cognitive impairment and Alzheimer's disease. In this updated review, we examined the evidence from the last 18 months regarding nutrition senolytics, with a focus on cognitive ageing among older adults.
RECENT FINDINGS: Overall, 19 systematic reviews and 17 intervention studies were included. Studies failed to provide evidence of nutritional senolytic agents or senescence-associated secretory phenotype (SASP) suppressors, for oral supplements providing beneficial effects on cognitive ageing among older adults. The protective role of food sources such as berries and nuts, and dietary patterns of Mediterranean diet and Mediterranean-DASH diet Intervention for Neurodegenerative Delay diet against cognitive decline or risk of dementia have been mostly supported by recent studies.
SUMMARY: The present review gathered additional evidence for both oral supplements and foods/diets rich in nutritional senolytic agents or SASP suppressors on cognitive health among older adults. In pursuing antiageing strategies, the importance of whole foods and healthy diets should not be overlooked, future studies are warranted on long-term effects and cytotoxicity of nutritional senolytics.

DOI: https://doi.org/10.1097/MCO.0000000000000796
Milbank Q. 2021 Nov 23.

A US State Index of Successful Aging: Differences Between States and Over Time.

AGING SOCIETY RESEARCH NETWORK

  Policy Points The focus of successful aging is on the social contexts that enable individuals to be productively engaged and secure, with an emphasis on equity. There is currently no index to measure progress towards this goal at the US state level. We developed an empirical index for the evaluation of US state adaptation to societal aging across five critical domains that support successful population aging: (1) productivity and engagement, (2) security, (3) equity, (4) cohesion, and (5) well-being. Our index shows substantial variability over time and is not overly influenced by the performance of an individual domain. This suggests that it can be used to monitor state progress over time toward the goal of supporting successful aging. Rather than a major national trend, there are large between-state differences and changes in our index over time. This suggests individual US state policies and programs, as well as local economic conditions, may have a substantial impact on adaptations to societal aging.
CONTEXT: Although it is recognized that aspects of US state environments impact the likelihood that older adults age successfully, there is currently no reliable and comprehensive measure of contexts that best support successful aging at a state level. The current project adapts a multidimensional index previously used to assess adaptation to successful aging in developed countries and applies it to the 50 US states and the District of Columbia.
METHODS: We obtained data from multiple sources for all 50 US states and the District of Columbia from 2003 to 2017 in order to measure five distinct domains that define successful population aging: (1) productivity and engagement, (2) security, (3) equity, (4) cohesion, and (5) well-being. We created a ranking of states for the year 2017 based on these domains, and also examined how individual US state rankings changed over time from 2003 to 2017.
FINDINGS: The level of adaptation to successful aging varied substantially between states and over time. The highest-ranked states in 2017 were Vermont, Hawaii, Iowa, Colorado, and New Hampshire, and the lowest-ranked states were Louisiana, Arkansas, Kentucky, West Virginia, and Mississippi. Mississippi, South Carolina, Iowa, Arizona, and Delaware had the greatest improvement in their ranking over the period of 2003 to 2017. Our findings were generally robust to the weighting scheme used and were not overly influenced by any particular domain.
CONCLUSIONS: The US State Index of Successful Aging can be used to monitor US state progress in promoting the well-being and health of aging populations. Factors driving the changes in the index remain to be elucidated.

Keywords:  aging; metrics; policy; states; successful aging

DOI:  https://doi.org/10.1111/1468-0009.12542
Stem Cell Rev Rep. 2021 Nov 23.

New Directions in Research on Aging.

Andrzej Bartke.

  Biology of aging is an active and rapidly expanding area of biomedical research. Over the years, focus of work in this field has been gradually shifting from studying the effects and symptoms of aging to searching for mechanisms of the aging process. Progress of this work led to an additional shift from looking for "the mechanism" of aging and formulating the corresponding "theories of aging" to appreciation that aging represents a net result of multiple physiological changes and their intricate interactions. It was also shown that mechanisms of aging include nutrient-dependent signaling pathways which have been remarkably conserved in the course of the evolution. Another important development in this field is increased emphasis on searching for pharmacological and environmental interventions that can extend healthspan or influence other aspects of aging. Progress in understanding the key role of aging as a risk factor for chronic disease provides impetus for these studies. Data from the recent pandemic provided additional evidence for the impact of age on resilience. Progress of work in this area also was influenced by major analytical and technological advances, including greatly improved methods for the study of gene expression, protein, lipids, and metabolites profiles, enhanced ability to produce various genetic modifications and novel approaches to assessment of biological age. Progress in research on the biology of aging provides reasons for optimism about the chances that safe and widely applicable anti-aging interventions with significant benefits for both individual and public health will be developed in the not too distant future.

Keywords:  Aging; Geroscience; Healthspan; Interventions; Lifespan

DOI:  https://doi.org/10.1007/s12015-021-10305-9
Innov Aging. 2021 ;5(4): igab035

Negative Perception of Aging Is Associated With Frailty Transitions Within a Cohort of Sexual Minority Men.

Karen Nieves-Lugo, Deanna Ware, Keri Althoff, Mark Brennan-Ing, Steven Meanley, Andre L Brown, Sabina A Haberlen, Mary Masters, James E Egan, Mackey R Friedman, Michael Plankey.

   Background and Objectives: Older people have an increased risk of developing frailty, an age-related clinical syndrome associated with worse health outcomes. This study examined the effect of self-perception of aging (ie, age discrepancy-individuals feel younger/older than their chronological age and aging satisfaction) on frailty transitions.
Research Design and Methods: We use longitudinal data from 549 HIV-/499 HIV+ sexual minority men aged 50 years or older enrolled in the Multicenter AIDS Cohort Study. To test the association of self-perception of aging on transitions between states of frailty (nonfrail/frail), defined using Fried Frailty Phenotype, a multinomial modeling was used.
Results: With remaining nonfrail as the referent group, participants reporting low aging satisfaction (vs moderate aging satisfaction) had increased odds of transitioning from nonfrail to frail (odds ratio [OR]: 2.72; 95% confidence interval [CI]: 1.56-4.74), frail to nonfrail (OR: 3.40; 95% CI: 1.62-7.12), or remaining frail (frail to frail; OR: 6.64; 95% CI: 3.88-11.38). Participants reporting older subjective age (vs no age discrepancy) had increased odds of transitioning from nonfrail to frail (OR: 2.50; 95% CI: 1.11-5.64), frail to nonfrail (OR: 4.47; 95% CI: 1.85-10.81), or remaining frail (frail to frail; OR: 5.68; 95% CI: 3.06-10.56). High aging satisfaction and younger subjective age were not statistically associated with frailty transitions.
Discussion and Implications: Our findings show that negative self-perception of aging (ie, older subjective age and low aging satisfaction) is associated with frailty transitions (nonfrail to frail, frail to nonfrail, and frail to frail) when compared to remaining nonfrail.

Keywords:  Attitudes and perception toward aging/aged; HIV/AIDS; Quantitative research methods; Sexual minority men

DOI:  https://doi.org/10.1093/geroni/igab035
Food Funct. 2021 Nov 25.

Anti-aging effects of the fermented anthocyanin extracts of purple sweet potato on Caenorhabditis elegans.

Jichun Zhao, Jie Yu, Qi Zhi, Tingting Yuan, Xiaojuan Lei, Kaifang Zeng, Jian Ming.

Anthocyanins have anti-inflammatory, anticarcinogenic and antioxidant properties and anti-aging effects as well as potential application as pigments. The metabolism of anthocyanins in fermented food has attracted increasing attention. However, the effect of lactic acid bacteria (LAB) fermentation on its anti-aging activity remains mostly unknown. The current study aimed to investigate the compositions, antioxidant activities and anti-aging effect of fermented purple sweet potato anthocyanins (FSPA) on aging Caenorhabditis elegans compared to raw purple sweet potato anthocyanins (PSPA). Results showed that anthocyanins were degraded into more bioavailable phenolic acids by Weissella confusa fermentation. PSPA and FSPA can extend the lifespan of C. elegans by 26.7% and 37.5%, respectively, through improving the activity of antioxidant enzymes as well as decreasing MDA content, ROS levels and lipofuscin accumulation. Pretreatment of the worms with PSPA and FSPA induced their potential to resist to thermal tolerance and oxidative stress, and FSPA exerted a higher anti-stress effect than PSPA. Moreover, FSPA supplementation upregulated the mRNA expressions of genes daf-16, hsp-16.2, sir-2.1, skn-1 and sod-3 and downregulated the expression of daf-2 in the nematodes, whereas PSPA only induced the increase in the expressions of sir-2.1, skn-1 and sod-3. Overall, FSPA can improve stress resistance and extend the lifespan of C. elegans by both insulin/IGF-1 signaling pathway and dietary restriction pathway, providing a theoretical basis for the application of PSPA in fermented food as functional pigments.

DOI: https://doi.org/10.1039/d1fo02671b
Nutrients. 2021 Oct 22. pii: 3728. [Epub ahead of print]13(11):

Effects of Nutrition on Cognitive Function in Adults with or without Cognitive Impairment: A Systematic Review of Randomized Controlled Clinical Trials.

Laia Gutierrez, Alexandre Folch, Melina Rojas, José Luis Cantero, Mercedes Atienza, Jaume Folch, Antoni Camins, Agustín Ruiz, Christopher Papandreou, Mònica Bulló.

  New dietary approaches for the prevention of cognitive impairment are being investigated. However, evidence from dietary interventions is mainly from food and nutrient supplement interventions, with inconsistent results and high heterogeneity between trials. We conducted a comprehensive systematic search of randomized controlled trials (RCTs) published in MEDLINE-PubMed, from January 2018 to July 2021, investigating the impact of dietary counseling, as well as food-based and dietary supplement interventions on cognitive function in adults with or without cognitive impairment. Based on the search strategy, 197 eligible publications were used for data abstraction. Finally, 61 articles were included in the analysis. There was reasonable evidence that dietary patterns, as well as food and dietary supplements improved cognitive domains or measures of brain integrity. The Mediterranean diet showed promising results, whereas the role of the DASH diet was not clear. Healthy food consumption improved cognitive function, although the quality of these studies was relatively low. The role of dietary supplements was mixed, with strong evidence of the benefits of polyphenols and combinations of nutrients, but with low evidence for PUFAs, vitamin D, specific protein, amino acids, and other types of supplements. Further well-designed RCTs are needed to guide the development of dietary approaches for the prevention of cognitive impairment.

Keywords:  Alzheimer’s disease; cognitive impairment; diet; dietary interventions; food; healthy; subjective cognitive decline; supplements

DOI:  https://doi.org/10.3390/nu13113728
Aging Ment Health. 2021 Nov 22. 1-9

Number of ideas in spontaneous speech predicts cognitive impairment and frailty in community-dwelling older adults nine years later.

Túlia Fernanda Meira Garcia, Catherine Nicol de Aravena Vallero, Daniela de Assumpção, Ivan Aprahamian, Yassuda Mônica Sanches, Flávia Silva Arbex Borim, Anita Liberalesso Neri.

   OBJECTIVE: To investigate the associations between linguistic parameters in spontaneous speech at baseline and cognitive impairment and frailty nine years later.
METHODS: A prospective analysis was carried out on data of the Frailty in Brazilian Older People Study (FIBRA) Study, a population-based study on frailty. From a probabilistic sample of 384 individuals aged 65 and older at baseline (2008-2009), 124 aged 73 years and older at follow-up were selected, as they had scored above the cutoff values of cognitive screening for dementia adjusted by years of schooling at baseline and had answered to the question What is healthy aging and had no frailty at baseline. Verbal responses were submitted to content analysis and had its ideas and words counted. Number of ideas corresponded to the frequency of meaning categories and number of words to all identified significant textual elements in the text constituted by the sample answers to that question.
RESULTS: Multivariate logistic regression analyses, controlling for the effects of age, sex, and education, showed that individuals with a high number of ideas at baseline had lower chance of having cognitive impairment (OR = 0.39; 95% CI 0.22 - 0.69) and frailty (OR 0.66; 95% CI 0.44 - 0.99) nine years later than those with low number of ideas.
CONCLUSIONS: Higher number of ideas, but not number of words, in spontaneous speech seems to be associated to a more positive prognosis in mental and physical health nine years later. Linguistic markers may be used to predict cognitive impairment and frailty in older individuals.

Keywords:  Verbal behavior; cognition; frailty; longitudinal studies; older adults

DOI:  https://doi.org/10.1080/13607863.2021.1998347
Nature. 2021 Nov;599(7886): 550-552

How record wildfires are harming human health.

Max Kozlov.



Keywords:  Climate change; Health care; Medical research

DOI:  https://doi.org/10.1038/d41586-021-03496-1
Sci Rep. 2021 Nov 26. 11(1): 23020

The effect of smiling on the perceived age of male and female faces across the lifespan.

Tzvi Ganel, Melvyn A Goodale.

Previous research has shown an unintuitive effect of facial expression on perceived age: smiling faces are perceived as older compared to neutral faces of the same people. The aging effect of smiling (AES), which is thought to result from the presence of smile-related wrinkles around the eyes, contradicts the common belief that smiling faces should be perceived as younger, not older. Previous research, however, has focused on faces of young adults, where the absence of inherent, age-related wrinkles and other age signs is offset by the weight of the smile-related wrinkles. In a series of experiments, we tested whether the AES extends to male and female faces in older age groups. We replicated the AES in young adults (20-39) and showed that it disappeared in older adults (60-79) of both genders. For photos of middle-aged adults (40-59), however, AES was found only for male, but not for female faces, who showed fewer and less prominent smile-related wrinkles. The results suggest that a person's apparent age is perceived in a holistic manner in which age-related cues in the region of the eyes are weighted against age cues in other regions of the face.

DOI: https://doi.org/10.1038/s41598-021-02380-2
Biomedicines. 2021 Nov 15. pii: 1693. [Epub ahead of print]9(11):

Hospital Frailty Risk Score Is Independently Associated with Mortality and Encephalopathy in Hospitalized Patients with Hepatocellular Carcinoma.

Daryl Ramai, Khoi P Dang-Ho, Anjali Kewalramani, Praneeth Bandaru, Rodolfo Sacco, Luca Giacomelli, Aashni Shah, Simonetta Papa, Francesca Cappellini, Fabio Perversi, Sara di Nunzio, Antonio Facciorusso.

  Frailty represents a state of vulnerability to multiple internal physiologic factors, as well as external pressures, and has been associated with clinical outcomes. We aim to understand the impact of frailty on patients admitted with hepatocellular carcinoma (HCC) by using the validated Hospital Frailty Risk Score, which is implemented in several hospitals worldwide. We conducted a nation-wide retrospective cohort study to determine the effect of frailty on the risk of in-patient mortality, hepatic encephalopathy, length of stay and cost. Frailty was associated with a 4.5-fold increased risk of mortality and a 2.3-fold increased risk of hepatic encephalopathy. Adjusted Cox regression showed that frailty was correlated with increased risk of in-patient mortality (hazard ratio: 2.3, 95% CI 1.9-2.8, p < 0.001). Frail HCC patients had longer hospital stay (median 5 days) vs. non-frail HCC patients (median 3 days). Additionally, frail patients had higher total costs of hospitalization ($40,875) compared with non-frail patients ($31,667). Frailty is an independent predictor of hepatic encephalopathy and in-patient mortality. Frailty is a surrogate marker of hospital length of stay and cost.

Keywords:  frailty; hepatocellular carcinoma; outcomes

DOI:  https://doi.org/10.3390/biomedicines9111693
BMC Med. 2021 Nov 24. 19(1): 280

Adherence to the Mediterranean diet assessed by a novel dietary biomarker score and mortality in older adults: the InCHIANTI cohort study.

Nicole Hidalgo-Liberona, Tomás Meroño, Raul Zamora-Ros, Montserrat Rabassa, Richard Semba, Toshiko Tanaka, Stefania Bandinelli, Luigi Ferrucci, Cristina Andres-Lacueva, Antonio Cherubini.

   BACKGROUND: Dietary biomarkers may complement dietary intake assessment made by dietary questionnaires. We developed an a-posteriori dietary biomarkers score based on Mediterranean diet food groups and evaluated its association with mortality.
METHODS: 642 participants (56% female), aged ≥65 years, with complete data on dietary biomarkers were followed during 20 years in the InCHIANTI cohort study (Tuscany, Italy). The main outcomes were all-cause, cardiovascular, and cancer mortality. Dietary biomarkers were selected from literature and from correlation analyses with dietary intakes of Mediterranean diet food groups in the study. The baseline levels of the following dietary biomarkers were chosen: urinary total polyphenols and resveratrol metabolites, and plasma carotenoids, selenium, vitamin B12, linolenic, eicosapentaenoic and docosahexaenoic acids, and the mono-unsaturated/saturated fatty acid ratio. Associations of the Mediterranean diet score using dietary biomarkers and a validated food frequency questionnaire (FFQ) (as tertiles) with mortality were assessed through Cox regression.
RESULTS: During the 20-year follow-up [median (Q1-Q3), 14 (8-18) years], and 435 deaths occurred (139 from cardiovascular diseases and 89 from cancer-related causes). In the fully adjusted models, the dietary biomarker-Mediterranean diet score was inversely associated with all-cause (HRT3vs.T1 0.72; 95%CI 0.56-0.91) and cardiovascular (HRT3vs.T1 0.60; 95%CI 0.38-0.93), but not with cancer mortality. Associations between the FFQ-Mediterranean diet score and mortality were not statistically significant.
CONCLUSIONS: A greater adherence at baseline to a Mediterranean diet assessed by a dietary biomarker score was associated with a lower risk of mortality in older adults during a 20-year follow-up. The measurement of dietary biomarkers may contribute to guide individualized dietary counseling to older people.
TRIAL REGISTRATION: NCT01331512.

Keywords:  Carotenoids; Dietary biomarkers; Dietary questionnaires; Mediterranean diet; Mortality; Older adults; Polyphenols

DOI:  https://doi.org/10.1186/s12916-021-02154-7
Cancers (Basel). 2021 Nov 15. pii: 5720. [Epub ahead of print]13(22):

Geriatric Oncology: From Research to Clinical Practice.

Nienke A de Glas.

The incidence of cancer in older adults is strongly increasing due to the ageing of the population [...].

DOI: https://doi.org/10.3390/cancers13225720
J Am Geriatr Soc. 2021 Nov 27.

Clinician knowledge and behaviors related to the 4Ms framework of Age-Friendly Health Systems.

Sarah Lesser, Stanislav Zakharkin, Christina Louie, Marcus R Escobedo, John Whyte, Terry Fulmer.

   BACKGROUND: The Age-Friendly Health Systems (AFHS) aims to improve the experience of care for adults aged 65 years and older through the 4Ms framework, an evidence-based approach to care planning that emphasizes what matters most to the older person, mentation, mobility, and medication. The aim of this study was to examine clinicians' attitudes, knowledge, and practices concerning AFHS and the 4Ms.
METHODS: We surveyed U.S.-based health care providers randomly identified from the Medscape database. The sample was weighted based on sex, U.S. Census region, and ethnic diversity of health occupations. We examined the differences between cohorts using proportions tests and logistic regression models.
RESULTS: More than 90% of clinicians (n = 1684) agreed that "older patients require a different approach to care than younger patients." Fifty percent of clinicians "always" take the age of their patient into consideration when determining care. A majority of clinicians said they discuss each of the 4Ms with older patients and/or their family caregivers. Screening for depression and review of high-risk medication use are among the leading types of age-friendly care that clinicians provide to older patients. A minority of clinicians are asking older adults about and aligning the care plan with What Matters.
CONCLUSIONS: A majority of clinicians acknowledged the benefits of providing care via AFHS but reported limited knowledge of the specificities of the 4Ms framework and are not necessarily taking the age of their patients into consideration when determining the best form of care. Health care settings that have implemented the 4Ms framework appear to be doing so in an incomplete way. Our study reinforces the case for training primary care providers on how to adopt the evidence-based 4Ms framework in clinical practice effectively and consistently.

Keywords:  4Ms framework; Age-Friendly Health Systems; health care

DOI:  https://doi.org/10.1111/jgs.17571
Diabetes Metab Syndr Obes. 2021 ;14 4535-4546

Comparison of Antiobesity Effects of Adipose-Derived Stromal/Stem Cells from Different Sources in a Natural Aging Model.

Yu Zhu, Tao Wang, Shuangli He, Shiming Pu, Hongxia Zhao, Zuping Zhou, Qiong Wu.

   Purpose: Our previous study found that white adipose stem cells (W-ASCs) derived from abdominal and femoral sulcus white adipose stem cells (ASCs) have antiaging and age-related obesity effects. Whether interscapular brown adipose stem cells (B-ASCs) have the same effect has not been reported. The study objective was to compare the effects of ASCs from different tissues on aging and aging-related obesity.
Patients and Methods: C57BL/6J mice at 22 months of age were transplanted with either B-ASCs or W-ASCs from young mice at 2 months of age. Changes in body weight, biochemistry, cytokines, hormone secretion, cell senescence, lipid metabolism, and ASC function were assessed after transplanted 1 month.
Results: W-ASCs were superior to B-ASCs as aging and age-related obesity indicators, based on change in body weight, organ weight, antioxidant and anti-inflammatory activity, lipid metabolism, and liver and kidney function.
Conclusion: Difference in the tissue source was reflected by the heterogeneity of antiaging and age-related obesity effects of transplanted ASCs. Based on the study results, we recommend W-ASCs over B-ASCs in aging and age-related obesity applications.

Keywords:  adipose-derived stromal/stem cells; aging; different tissue sources; obesity

DOI:  https://doi.org/10.2147/DMSO.S334044
Int J Mol Sci. 2021 Nov 18. pii: 12463. [Epub ahead of print]22(22):

Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions.

Faiz-Ul Hassan, Asif Nadeem, Zhipeng Li, Maryam Javed, Qingyou Liu, Jahanzaib Azhar, Muhammad Saif-Ur Rehman, Kuiqing Cui, Saif Ur Rehman.

  Peroxisome proliferator-activated receptors (PPARs) are the nuclear receptors that could mediate the nutrient-dependent transcriptional activation and regulate metabolic networks through energy homeostasis. However, these receptors cannot work properly under metabolic stress. PPARs and their subtypes can be modulated by nutrigenomic interventions, particularly under stress conditions to restore cellular homeostasis. Many nutrients such as polyunsaturated fatty acids, vitamins, dietary amino acids and phytochemicals have shown their ability for potential activation or inhibition of PPARs. Thus, through different mechanisms, all these nutrients can modulate PPARs and are ultimately helpful to prevent various metabolic disorders, particularly in transition dairy cows. This review aims to provide insights into the crucial role of PPARs in energy metabolism and their potential modulation through nutrigenomic interventions to improve energy homeostasis in dairy animals.

Keywords:  PPARs; dairy animals; energy homeostasis; nuclear receptors; nutrigenomics

DOI:  https://doi.org/10.3390/ijms222212463
Cells. 2021 Oct 21. pii: 2823. [Epub ahead of print]10(11):

Cardiotoxicity of Antineoplastic Therapies and Applications of Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Mo-Fan Huang, Lon Kai Pang, Yi-Hung Chen, Ruiying Zhao, Dung-Fang Lee.

  The therapeutic landscape for the treatment of cancer has evolved significantly in recent decades, aided by the development of effective oncology drugs. However, many cancer drugs are often poorly tolerated by the body and in particular the cardiovascular system, causing adverse and sometimes fatal side effects that negate the chemotherapeutic benefits. The prevalence and severity of chemotherapy-induced cardiotoxicity warrants a deeper investigation of the mechanisms and implicating factors in this phenomenon, and a consolidation of scientific efforts to develop mitigating strategies. Aiding these efforts is the emergence of induced pluripotent stem cells (iPSCs) in recent years, which has allowed for the generation of iPSC-derived cardiomyocytes (iPSC-CMs): a human-based, patient-derived, and genetically variable platform that can be applied to the study of chemotherapy-induced cardiotoxicity and beyond. After surveying chemotherapy-induced cardiotoxicity and the associated chemotherapeutic agents, we discuss the use of iPSC-CMs in cardiotoxicity modeling, drug screening, and other potential applications. Improvements to the iPSC-CM platform, such as the development of more adult-like cardiomyocytes and ongoing advances in biotechnology, will only enhance the utility of iPSC-CMs in both basic science and clinical applications.

Keywords:  cancer; cardiotoxicity; chemotherapy; differentiation; disease model; induced pluripotency; personalized medicine; pharmacogenomics; reprogramming; stem cell

DOI:  https://doi.org/10.3390/cells10112823
Cells. 2021 Oct 28. pii: 2924. [Epub ahead of print]10(11):

Role of Deep Learning in Predicting Aging-Related Diseases: A Scoping Review.

Jyotsna Talreja Wassan, Huiru Zheng, Haiying Wang.

  Aging refers to progressive physiological changes in a cell, an organ, or the whole body of an individual, over time. Aging-related diseases are highly prevalent and could impact an individual's physical health. Recently, artificial intelligence (AI) methods have been used to predict aging-related diseases and issues, aiding clinical providers in decision-making based on patient's medical records. Deep learning (DL), as one of the most recent generations of AI technologies, has embraced rapid progress in the early prediction and classification of aging-related issues. In this paper, a scoping review of publications using DL approaches to predict common aging-related diseases (such as age-related macular degeneration, cardiovascular and respiratory diseases, arthritis, Alzheimer's and lifestyle patterns related to disease progression), was performed. Google Scholar, IEEE and PubMed are used to search DL papers on common aging-related issues published between January 2017 and August 2021. These papers were reviewed, evaluated, and the findings were summarized. Overall, 34 studies met the inclusion criteria. These studies indicate that DL could help clinicians in diagnosing disease at its early stages by mapping diagnostic predictions into observable clinical presentations; and achieving high predictive performance (e.g., more than 90% accurate predictions of diseases in aging).

Keywords:  PRISMA; aging; classification; deep learning; prediction

DOI:  https://doi.org/10.3390/cells10112924
J Fam Pract. 2021 Oct;70(8): 376-385

A 4-pronged approach to foster healthy aging in older adults.

Lynn M Wilson, Angela L Colistra, Elisa Giusto, Susan E Hansen.

Monitoring patients' health, mobility, mentation, and ability to maintain social connections can help you promote healthy aging for your older patients.

DOI: https://doi.org/10.12788/jfp.0276
Nat Rev Immunol. 2021 Nov 23.

Immune ageing at single-cell resolution.

Denis A Mogilenko, Irina Shchukina, Maxim N Artyomov.

Ageing leads to profound alterations in the immune system and increases susceptibility to some chronic, infectious and autoimmune diseases. In recent years, widespread application of single-cell techniques has enabled substantial progress in our understanding of the ageing immune system. These comprehensive approaches have expanded and detailed the current views of ageing and immunity. Here we review a body of recent studies that explored how the immune system ages using unbiased profiling techniques at single-cell resolution. Specifically, we discuss an emergent understanding of age-related alterations in innate and adaptive immune cell populations, antigen receptor repertoires and immune cell-supporting microenvironments of the peripheral tissues. Focusing on the results obtained in mice and humans, we describe the multidimensional data that align with established concepts of immune ageing as well as novel insights emerging from these studies. We further discuss outstanding questions in the field and highlight techniques that will advance our understanding of immune ageing in the future.

DOI: https://doi.org/10.1038/s41577-021-00646-4
Sci Rep. 2021 Nov 25. 11(1): 22907

Development of a new clinical index to easily assess frailty of elderly patients with multiple myeloma in Asian population.

Ho Sup Lee, JiHyun Lee, Jae-Cheol Jo, Sung-Hoon Jung, Je-Jung Lee, Dajung Kim, Sangjin Lee, Kevin Song.

The number of elderly people is rapidly growing, and the proportion of elderly patients with multiple myeloma (MM) continues to increase. This study aimed to develop a frailty assessment tool based on clinical data and to estimate its feasibility in elderly patients with MM. This study analyzed data from 728 elderly transplant-ineligible patients with newly diagnosed MM who were treated between January 2010 and October 2019. Our clinical frailty index included age (< 75, and ≥ 75 years), Charlson comorbidity index (CCI; < 3 and ≥ 3), and Eastern Cooperative Oncology Group performance status score (ECOG score; 0, 1-2, and ≥ 3). Patients were classified as fit, intermediate, or frail if they had a score of 0, 1, or ≥ 2, respectively. The overall survival rates differed significantly according to frailty (fit vs. intermediate: hazard ratio [HR] = 2.41; 95% confidence interval [CI] = 1.43-4.06; P = 0.001; fit vs. frail: HR = 4.61; 95% CI = 2.74-7.77; P < 0.001 and intermediate vs. frail: HR = 1.91, 95% CI = 1.49-2.45, P < 0.001, respectively). The frail had significantly shorter EFS compared with the fit and intermediate group in our frailty index (fit vs. intermediate: HR = 1.34, 95% CI = 0.92-1.96, P = 0.132; fit vs. frail: HR = 2.06, 95% CI = 1.40-3.02, P < 0.001; and intermediate vs. frail: HR = 1.53, 95% CI = 1.22-1.92, P < 0.001, respectively). The new clinical frailty index, which is based on age, CCI, and ECOG PS, can easily assess frailty in elderly patients with MM and can be helpful in predicting survival outcomes in real world clinical setting.

DOI: https://doi.org/10.1038/s41598-021-02433-6
Aging Cell. 2021 Nov 27. e13488

Metformin treatment of diverse Caenorhabditis species reveals the importance of genetic background in longevity and healthspan extension outcomes.

Brian Onken, Christine A Sedore, Anna L Coleman-Hulbert, David Hall, Erik Johnson, Eleanor Grace Jones, Stephen A Banse, Phu Huynh, Suzhen Guo, Jian Xue, Esteban Chen, Girish Harinath, Anna C Foulger, Elizabeth A Chao, June Hope, Dipa Bhaumik, Todd Plummer, Delaney Inman, Mackenzie Morshead, Max Guo, Gordon J Lithgow, Patrick C Phillips, Monica Driscoll.

  Metformin, the most commonly prescribed anti-diabetes medication, has multiple reported health benefits, including lowering the risks of cardiovascular disease and cancer, improving cognitive function with age, extending survival in diabetic patients, and, in several animal models, promoting youthful physiology and lifespan. Due to its longevity and health effects, metformin is now the focus of the first proposed clinical trial of an anti-aging drug-the Targeting Aging with Metformin (TAME) program. Genetic variation will likely influence outcomes when studying metformin health effects in human populations. To test for metformin impact in diverse genetic backgrounds, we measured lifespan and healthspan effects of metformin treatment in three Caenorhabditis species representing genetic variability greater than that between mice and humans. We show that metformin increases median survival in three C. elegans strains, but not in C. briggsae and C. tropicalis strains. In C. briggsae, metformin either has no impact on survival or decreases lifespan. In C. tropicalis, metformin decreases median survival in a dose-dependent manner. We show that metformin prolongs the period of youthful vigor in all C. elegans strains and in two C. briggsae strains, but that metformin has a negative impact on the locomotion of C. tropicalis strains. Our data demonstrate that metformin can be a robust promoter of healthy aging across different genetic backgrounds, but that genetic variation can determine whether metformin has positive, neutral, or negative lifespan/healthspan impact. These results underscore the importance of tailoring treatment to individuals when testing for metformin health benefits in diverse human populations.

Keywords:  anti-diabetes drug; biguanide; genetic diversity; healthspan; longevity

DOI:  https://doi.org/10.1111/acel.13488
Nat Immunol. 2021 Nov 22.

Shortage of aspartate in mitochondria fuels arthritis.

Marc Scherlinger, George C Tsokos.

DOI: https://doi.org/10.1038/s41590-021-01069-y
Nutrients. 2021 Oct 27. pii: 3835. [Epub ahead of print]13(11):

Pathophysiology of Vascular Calcification and Bone Loss: Linked Disorders of Ageing?

Jorge B Cannata-Andía, Natalia Carrillo-López, Osvaldo D Messina, Neveen A T Hamdy, Sara Panizo, Serge L Ferrari, On Behalf Of The International Osteoporosis Foundation Iof Working Group On Bone And Cardiovascular Diseases.

  Vascular Calcification (VC), low bone mass and fragility fractures are frequently observed in ageing subjects. Although this clinical observation could be the mere coincidence of frequent age-dependent disorders, clinical and experimental data suggest that VC and bone loss could share pathophysiological mechanisms. Indeed, VC is an active process of calcium and phosphate precipitation that involves the transition of the vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Among the molecules involved in this process, parathyroid hormone (PTH) plays a key role acting through several mechanisms which includes the regulation of the RANK/RANKL/OPG system and the Wnt/ß-catenin pathway, the main pathways for bone resorption and bone formation, respectively. Furthermore, some microRNAs have been implicated as common regulators of bone metabolism, VC, left ventricle hypertrophy and myocardial fibrosis. Elucidating the common mechanisms between ageing; VC and bone loss could help to better understand the potential effects of osteoporosis drugs on the CV system.

Keywords:  bone fractures; bone loss; fracture risk; mineral bone disorders; osteoporosis; vascular calcification

DOI:  https://doi.org/10.3390/nu13113835