bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2021–11–14
forty-four papers selected by
Ayesh Seneviratne, University of Toronto
  1. Multidimensional impact of the geriatric assessment in the cancer care of older adults.
  2. Can skin aging contribute to systemic inflammaging?
  3. Biomedicalization of end-of-life conversations with medically frail older adults - Malleable and senescent bodies.
  4. Regulation of NAD+ metabolism in aging and disease.
  5. SARS-CoV-2, COVID-19 and the Ageing Immune System.
  6. Myeloid Metabolism as a New Target for Rejuvenation?-Comments on Restoring Metabolism of Myeloid Cells Reverses Cognitive Decline in Ageing. Nature. 2021 Feb;590(7844):122-128.
  7. Association of frailty and chemotherapy-related adverse outcomes in geriatric patients with cancer: a pilot observational study in Taiwan.
  8. Hematopoietic Stem Cells and Regeneration.
  9. Enasidenib-induced differentiation promotes sensitivity to venetoclax in IDH2-mutated acute myeloid leukemia.
  10. Successful Aging Among Older LGBTQIA+ People: Future Research and Implications.
  11. Plasmalogens and Chronic Inflammatory Diseases.
  12. Altered Chromatin States Drive Cryptic Transcription in Aging Mammalian Stem Cells.
  13. Extracellular Vesicles: Footprints of environmental exposures in the aging process?
  14. Angiotensin II inhibition: a potential treatment to slow the progression of sarcopenia.
  15. Equity in focus: Iqaluit water contaminated, tuberculosis on the rise, blood ban easing.
  16. The prevalence of frailty and its associated factors in an Italian institutionalized older population: findings from the cross-sectional Alvise Cornaro Center Study.
  17. Cancers after hematopoietic cell transplantation for aplastic anemia-the importance of persistence.
  18. Diet composition influences the metabolic benefits of short cycles of very low caloric intake.
  19. Frailty and chronic respiratory disease: the need for a multidisciplinary care model.
  20. Charting host-microbe co-metabolism in skin aging and application to metagenomics data.
  21. Genomic expansion of Aldh1a1 protects beavers against high metabolic aldehydes from lipid oxidation.
  22. An inflammatory ageing clock to detect cardiovascular and other age-related diseases: a new approach to preventive medicine.
  23. Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release.
  24. Connecting copper and cancer: from transition metal signalling to metalloplasia.
  25. When Society Ages.
  26. Evolution of natural lifespan variation and molecular strategies of extended lifespan.
  27. Skeletal muscle aging, cellular senescence, and senotherapeutics: Current knowledge and future directions.
  28. Prevalence of Frailty in Middle-Aged Diabetic Population of Ahmedabad: A Cross-Sectional Study.
  29. Beetroot as a functional food with huge health benefits: Antioxidant, antitumor, physical function, and chronic metabolomics activity.
  30. Protocol to maintain single functional mouse hematopoietic stem cells in vitro without cell division.
  31. Clonal Hematopoiesis Is Associated With Higher Risk of Stroke.
  32. Nutritional status as a mediator between the age-related muscle loss and frailty in community-dwelling older adults.
  33. Successful ageing among a national community-dwelling sample of older adults in India in 2017-2018.
  34. Machine learning finds new AML subtypes.
  35. Syndecan-2 expression enriches for hematopoietic stem cells and regulates stem cell repopulating capacity.
  36. Patient-centered care in geriatric cardiology.
  37. Adherence to the DASH dietary pattern is associated with blood pressure and anthropometric indicators in Mexican adults.
  38. BCL-2 Expression in AML Patients over 65 Years: Impact on Outcomes across Different Therapeutic Strategies.
  39. Assessment of the health status of middle-aged and elderly men with head scale, SF-36, IIEF5, AMS, and IPSS.
  40. Treatment of COVID-19 with MSCs: how does it work?
  41. Herbal Medicine Compared to Placebo for Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.
  42. A dynamic duo.
  43. Aging Resistance of Silica Fume/Styrene-Butadiene-Styrene Composite-Modified Asphalt.
  44. Low-protein diet applied as part of combination therapy or stand-alone normalizes lifespan and tumor proliferation in a model of intestinal cancer.
  1. Cancer. 2021 Nov 11.
    Multidimensional impact of the geriatric assessment in the cancer care of older adults.
    Ishwaria M Subbiah, Isabel Tejero, Shabbir M H Alibhai.
      
    Keywords:  communication; frailty; geriatric assessment; older adult; randomized controlled trial
    DOI:  https://doi.org/10.1002/cncr.34009
  2. J Invest Dermatol. 2021 Oct 28. pii: S0022-202X(21)02402-7. [Epub ahead of print]
    Can skin aging contribute to systemic inflammaging?
    Suzanne M Pilkington, Silvia Bulfone-Paus, Christopher Em Griffiths, Rachel Eb Watson.
      
    Keywords:  Aging; Barrier function; Inflammation; Interventional Trials; Keratinocytes
    DOI:  https://doi.org/10.1016/j.jid.2021.09.032
  3. Soc Sci Med. 2020 Oct 09. pii: S0277-9536(20)30647-X. [Epub ahead of print] 113428
    Biomedicalization of end-of-life conversations with medically frail older adults - Malleable and senescent bodies.
    Celina Carter, Shan Mohammed, Ross Upshur, Pia Kontos.
      The common practice of delaying and/or avoiding end-of-life conversations with medically frail older adults is an important clinical issue. Most research investigating this practice focuses on clinician training and developing conversation skills. Little is known about the socio-political factors shaping the phenomenon of end-of-life conversations between clinicians and medically frail older patients. Using the critical lens of biomedicalization we consider how two dominant discourses, successful aging and frailty, and subsequent constructions of bodies as malleable or senescent, shape patient subjectivities and influence normative expectations about appropriate healthcare conversations and the consumption of biomedicine for medically frail adults. We highlight the uneven ways medically frail older adults are clinically positioned as successful or frail agers and briefly discuss how gender, class, and race may impact this tension and ambiguity. We conclude by arguing that end-of-life conversations with medically frail older adults is constrained by the pervasiveness of the successful aging discourse and the tendency within medical institutions to construct older bodies as malleable and in need of medical intervention to promote health and longevity.
    Keywords:  Advance care planning; Biomedicalization; Discourse; End-of-life conversations; Frailty; Older adults; Successful aging
    DOI:  https://doi.org/10.1016/j.socscimed.2020.113428
  4. Metabolism. 2021 Oct 28. pii: S0026-0495(21)00223-7. [Epub ahead of print]126 154923
    Regulation of NAD+ metabolism in aging and disease.
    Xiaogang Chu, Raghavan Pillai Raju.
      More than a century after discovering NAD+, information is still evolving on the role of this molecule in health and diseases. The biological functions of NAD+ and NAD+ precursors encompass pathways in cellular energetics, inflammation, metabolism, and cell survival. Several metabolic and neurological diseases exhibit reduced tissue NAD+ levels. Significantly reduced levels of NAD+ are also associated with aging, and enhancing NAD+ levels improved healthspan and lifespan in animal models. Recent studies suggest a causal link between senescence, age-associated reduction in tissue NAD+ and enzymatic degradation of NAD+. Furthermore, the discovery of transporters and receptors involved in NAD+ precursor (nicotinic acid, or niacin, nicotinamide, and nicotinamide riboside) metabolism allowed for a better understanding of their role in cellular homeostasis including signaling functions that are independent of their functions in redox reactions. We also review studies that demonstrate that the functional effect of niacin is partially due to the activation of its cell surface receptor, GPR109a. Based on the recent progress in understanding the mechanism and function of NAD+ and NAD+ precursors in cell metabolism, new strategies are evolving to exploit these molecules' pharmacological potential in the maintenance of metabolic balance.
    Keywords:  NAD; Niacin; Niacin receptor; Nicotinamide adenine mononucleotide; Nicotinamide riboside
    DOI:  https://doi.org/10.1016/j.metabol.2021.154923
  5. Nat Aging. 2021 Sep;1(9): 769-782
    SARS-CoV-2, COVID-19 and the Ageing Immune System.
    Juliet M Bartleson, Dina Radenkovic, Anthony J Covarrubias, David Furman, Daniel A Winer, Eric Verdin.
      The coronavirus disease 2019 (COVID-19) pandemic is a global health threat with particular risk for severe disease and death in older adults and in adults with age-related metabolic and cardiovascular disease. Recent advances in the science of ageing have highlighted how ageing pathways control not only lifespan but also healthspan, the healthy years of life. Here, we discuss the ageing immune system and its ability to respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We specifically focus on the intersect of severe COVID-19 and immunosenescence to highlight pathways that may be determinant for the risk of complications and death following infection with SARS-CoV-2. New or adapted therapeutics that target ageing-associated pathways may be important tools to reduce the burden of death and long-term disability caused by this pandemic. Proposed interventions aimed at immunosenescence could enhance immune function not only in the elderly but in susceptible younger individuals as well, ultimately improving complications of severe COVID-19 for all ages.
    DOI:  https://doi.org/10.1038/s43587-021-00114-7
  6. Immunometabolism. 2021 ;3(4): e210034
    Myeloid Metabolism as a New Target for Rejuvenation?-Comments on Restoring Metabolism of Myeloid Cells Reverses Cognitive Decline in Ageing. Nature. 2021 Feb;590(7844):122-128.
    Marlen Knobloch, Rosa C Paolicelli.
      Research led by Katrin Andreasson suggests that fixing age-induced metabolic defects in myeloid cells would suffice to reverse cognitive impairment and to restore synaptic plasticity to the level of young subjects, at least in mice. This opens up the possibility to develop rejuvenating strategies by targeting immune dysfunction.
    Keywords:  ageing; metabolism; myeloid cells; prostaglandin E2; rejuvenation
    DOI:  https://doi.org/10.20900/immunometab20210034
  7. Aging (Albany NY). 2021 Nov 08. 13(undefined):
    Association of frailty and chemotherapy-related adverse outcomes in geriatric patients with cancer: a pilot observational study in Taiwan.
    Ya-Wen Ho, Woung-Ru Tang, Shih-Ying Chen, Shu-Hui Lee, Jen-Shi Chen, Yu-Shin Hung, Wen-Chi Chou.
       BACKGROUND: With the rapid growth of the elderly population and the increasing incidence of cancer, an increasing number of geriatric patients are receiving cancer treatment, making the selection of appropriate treatment an important issue. Increasing studies have confirmed that frailty can predict adverse outcomes in geriatric patients with cancer after treatment, but local data from Taiwan are lacking. Therefore, this study aimed to investigate the correlation between frailty and chemotherapy-related adverse outcomes in geriatric patients with cancer.
    MATERIAL AND METHODS: A total of 234 geriatric patients aged ≥65 years with cancer receiving chemotherapy were enrolled during the study period of September 2016 to November 2018. The collected data included: patients' basic demographics and Comprehensive Geriatric Assessment (CGA) before treatment, chemotherapy-related adverse outcomes, unexpected hospitalizations, and emergency department visits within 3 months of treatment. We investigated the association between frailty and chemotherapy-related adverse outcomes in geriatric patients with cancer using the chi-square test and logistic regression analysis.
    RESULTS: The prevalence of frailty in geriatric patients with cancer was 58.1%. Age, marital status, main caregiver, cancer type, and Eastern Cooperative Oncology Group performance status, and physical fitness were factors associated with frailty. Frail geriatric patients with cancer were at higher risk of chemotherapy-related adverse outcomes, such as grades 3-4 thrombocytopenia (odds ratio [OR] = 11.13, p = 0.021) and grades 3-4 hyponatremia (OR = 12.03, p = 0.017), than non-frail patients, and they were at increased risk of unexpected hospitalizations (OR = 2.15, p = 0.025) and emergency department visits (OR = 1.99, p = 0.039).
    CONCLUSIONS: Frailty is a common problem in geriatric patients with cancer and significantly impacts chemotherapy-related adverse outcomes. Our findings suggest that geriatric patients with cancer should undergo frail assessment prior to chemotherapy as a reference to guide future treatment decisions.
    Keywords:  chemotherapy-related adverse outcomes; comprehensive geriatric assessment; frailty; geriatric patients with cancer
    DOI:  https://doi.org/10.18632/aging.203673
  8. Cold Spring Harb Perspect Biol. 2021 Nov 08. pii: a040774. [Epub ahead of print]
    Hematopoietic Stem Cells and Regeneration.
    Mitch Biermann, Tannishtha Reya.
      Hematopoietic stem cell (HSC) regeneration is the remarkable process by which extremely rare, normally inactive cells of the bone marrow can replace an entire organ if called to do so by injury or harnessed by transplantation. HSC research is arguably the first quantitative single-cell science and the foundation of adult stem cell biology. Bone marrow transplant is the oldest and most refined technique of regenerative medicine. Here we review the intertwined history of the discovery of HSCs and bone marrow transplant, the molecular and cellular mechanisms of HSC self-renewal, and the use of HSCs and their derivatives for cell therapy.
    DOI:  https://doi.org/10.1101/cshperspect.a040774
  9. Leukemia. 2021 Nov 06.
    Enasidenib-induced differentiation promotes sensitivity to venetoclax in IDH2-mutated acute myeloid leukemia.
    Severine Cathelin, David Sharon, Amit Subedi, Dan Cojocari, Darren C Phillips, Joel D Leverson, Kyle J MacBeth, Brandon Nicolay, Rohini Narayanaswamy, Sebastien Ronseaux, Guowen Liu, Steven M Chan.
      
    DOI:  https://doi.org/10.1038/s41375-021-01468-y
  10. Front Psychiatry. 2021 ;12 756649
    Successful Aging Among Older LGBTQIA+ People: Future Research and Implications.
    Henrique Pereira, Debanjan Banerjee.
      
    Keywords:  LGBTQIA+; discrimination; healthy aging; old age; sexual minorities
    DOI:  https://doi.org/10.3389/fpsyt.2021.756649
  11. Front Physiol. 2021 ;12 730829
    Plasmalogens and Chronic Inflammatory Diseases.
    José Carlos Bozelli, Sayed Azher, Richard M Epand.
      It is becoming widely acknowledged that lipids play key roles in cellular function, regulating a variety of biological processes. Lately, a subclass of glycerophospholipids, namely plasmalogens, has received increased attention due to their association with several degenerative and metabolic disorders as well as aging. All these pathophysiological conditions involve chronic inflammatory processes, which have been linked with decreased levels of plasmalogens. Currently, there is a lack of full understanding of the molecular mechanisms governing the association of plasmalogens with inflammation. However, it has been shown that in inflammatory processes, plasmalogens could trigger either an anti- or pro-inflammation response. While the anti-inflammatory response seems to be linked to the entire plasmalogen molecule, its pro-inflammatory response seems to be associated with plasmalogen hydrolysis, i.e., the release of arachidonic acid, which, in turn, serves as a precursor to produce pro-inflammatory lipid mediators. Moreover, as plasmalogens comprise a large fraction of the total lipids in humans, changes in their levels have been shown to change membrane properties and, therefore, signaling pathways involved in the inflammatory cascade. Restoring plasmalogen levels by use of plasmalogen replacement therapy has been shown to be a successful anti-inflammatory strategy as well as ameliorating several pathological hallmarks of these diseases. The purpose of this review is to highlight the emerging role of plasmalogens in chronic inflammatory disorders as well as the promising role of plasmalogen replacement therapy in the treatment of these pathologies.
    Keywords:  aging; degenerative disorders; inflammation; metabolic disorders; oxidative stress; plasmalogen; plasmalogen replacement therapy; polyunsaturated fatty acids
    DOI:  https://doi.org/10.3389/fphys.2021.730829
  12. Nat Aging. 2021 Aug;1(8): 684-697
    Altered Chromatin States Drive Cryptic Transcription in Aging Mammalian Stem Cells.
    Brenna S McCauley, Luyang Sun, Ruofan Yu, Minjung Lee, Haiying Liu, Dena S Leeman, Yun Huang, Ashley E Webb, Weiwei Dang.
      A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing it extends yeast lifespan, though whether this occurs in mammals is unknown. We show that cryptic transcription is elevated in aged mammalian stem cells, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Precise mapping allowed quantification of age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Genomic regions undergoing such changes resemble known promoter sequences and are bound by TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies increased cryptic transcription in aged mammalian stem cells.
    DOI:  https://doi.org/10.1038/s43587-021-00091-x
  13. Curr Environ Health Rep. 2021 Nov 06.
    Extracellular Vesicles: Footprints of environmental exposures in the aging process?
    Paola Monti, Giulia Solazzo, Luca Ferrari, Valentina Bollati.
       PURPOSE OF THE REVIEW: Extracellular vesicles (EVs) are nano-sized lipid particles that participate in intercellular signaling through the trafficking of bioactive molecules from parental cells to recipient ones. This well-orchestrated communication system is crucial for the organism to respond to external cues in a coordinated manner; indeed, environmental and lifestyle exposures can modify both EV number and content, with consequences on cellular metabolism and homeostasis. In particular, a growing body of evidence suggests that exposome-induced changes in EV profile could regulate the aging process, both at the cellular and organismal levels. Here, we provide an overview of the role played by ambient-induced EVs on aging and age-related diseases. Among the several environmental factors that can affect the communication network operated by EVs, we focused on air pollution, ultraviolet light, diet, and physical exercise. Moreover, we performed a miRNA target analysis, to support the role of EV-miRNA emerging from the literature in the context of aging.
    RECENT FINDINGS: The overall emerging picture strongly supports a key regulatory role for EVs at the interface between external stimuli and cellular/organismal aging, thus providing novel insights into the molecular mechanisms linking a "healthy exposome" to well-being in old age. In addition, this knowledge will pave the way for research aimed at developing innovative antiaging strategies based on EVs.
    Keywords:  Extracellular vesicles; aging; air pollution; diet; physical exercise; ultraviolet exposure
    DOI:  https://doi.org/10.1007/s40572-021-00327-3
  14. Clin Sci (Lond). 2021 Nov 12. 135(21): 2503-2520
    Angiotensin II inhibition: a potential treatment to slow the progression of sarcopenia.
    Jeffrey Kingsley, Keiichi Torimoto, Tomoki Hashimoto, Satoru Eguchi.
      Sarcopenia is defined as the progressive and generalized loss of skeletal muscle mass and strength, which is associated with increased likelihood of adverse outcomes including falls, fractures, physical disability, and mortality. The etiology of sarcopenia has been postulated to be multifactorial with genetics, aging, immobility, nutritional deficiencies, inflammation, stress, and endocrine factors all contributing to the imbalance of muscle anabolism and catabolism. The prevalence of sarcopenia is estimated to range from 13 to 24% in adults over 60 years of age and up to 50% in persons aged 80 and older. As the population continues to age, the prevalence of sarcopenia continues to increase and is expected to affect 500 million people by the year 2050. Sarcopenia impacts the overall health of patients through limitations in functional status, increase in hospital readmissions, poorer hospital outcomes, and increase in overall mortality. Thus, there exists a need to prevent or reduce the occurrence of sarcopenia. Here, we explore the potential mechanisms and current studies regarding angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors on reducing the development of sarcopenia through the associated changes in cardiovascular function, renal function, muscle fiber composition, inflammation, endothelial dysfunction, metabolic efficiency, and mitochondrial function.
    Keywords:  ACE; ARB; Sarcopenia; angiotensin II
    DOI:  https://doi.org/10.1042/CS20210719
  15. CMAJ. 2021 Nov 08. 193(44): E1706-E1707
    Equity in focus: Iqaluit water contaminated, tuberculosis on the rise, blood ban easing.
    Greg Basky.
      
    DOI:  https://doi.org/10.1503/cmaj.1095970
  16. Aging Clin Exp Res. 2021 Nov 11.
    The prevalence of frailty and its associated factors in an Italian institutionalized older population: findings from the cross-sectional Alvise Cornaro Center Study.
    Alvise Cornaro Center Study Group
       BACKGROUND: While it is well established that frail older people have a higher risk of negative health outcomes, the prevalence of frailty and its associated factors in Italian older institutionalized population has never been investigated.
    AIMS: The aims of this study were to assess the prevalence of frailty and to identify its associated factors in an Italian residential care home population.
    METHODS: An observational cross-sectional study was designed to evaluate older people aged 70 or over of an Italian residential care home. A multidimensional assessment examining functional, geriatric, ophthalmic, and audiological domains was carried out to identify factors associated with frailty. Physical frailty was evaluated using Fried's criteria.
    RESULTS: Data analysis uncovered a 51.1% prevalence of pre-frailty and a 40.4% prevalence of frailty in the 94 eligible participants (64 females) whose data were complete. The multivariable analysis showed that a low education level (OR = 5.12, 95% CI 1.22-21.49), a low physical quality of life score (OR = 13.25, 95% CI 3.51-50.08), a low mental quality of life score (OR = 9.22, 95% CI 2.38-35.69), visual impairment (OR = 7.65, 95% CI 1.77-33.14), and hearing impairment (OR = 4.62, 95% CI 1.03-20.66) were independently associated with frailty.
    CONCLUSIONS: Frailty was found to be highly prevalent in the residential care home studied. Since frailty is a reversible condition, identifying the modifiable factors associated to it should be viewed as an important step in planning and implementing targeted, early prevention strategies.
    Keywords:  Associated-factors; Cross-sectional; Frailty; Prevalence; Residential care home
    DOI:  https://doi.org/10.1007/s40520-021-02020-9
  17. Bone Marrow Transplant. 2021 Nov 09.
    Cancers after hematopoietic cell transplantation for aplastic anemia-the importance of persistence.
    Alicia Rovó, André Tichelli.
      
    DOI:  https://doi.org/10.1038/s41409-021-01514-4
  18. Nat Commun. 2021 Nov 09. 12(1): 6463
    Diet composition influences the metabolic benefits of short cycles of very low caloric intake.
    Alberto Diaz-Ruiz, Tyler Rhinesmith, Laura C D Pomatto-Watson, Nathan L Price, Farzin Eshaghi, Margaux R Ehrlich, Jacqueline M Moats, Melissa Carpenter, Annamaria Rudderow, Sebastian Brandhorst, Julie A Mattison, Miguel A Aon, Michel Bernier, Valter D Longo, Rafael de Cabo.
      Diet composition, calories, and fasting times contribute to the maintenance of health. However, the impact of very low-calorie intake (VLCI) achieved with either standard laboratory chow (SD) or a plant-based fasting mimicking diet (FMD) is not fully understood. Here, using middle-aged male mice we show that 5 months of short 4:10 VLCI cycles lead to decreases in both fat and lean mass, accompanied by improved physical performance and glucoregulation, and greater metabolic flexibility independent of diet composition. A long-lasting metabolomic reprograming in serum and liver is observed in mice on VLCI cycles with SD, but not FMD. Further, when challenged with an obesogenic diet, cycles of VLCI do not prevent diet-induced obesity nor do they elicit a long-lasting metabolic memory, despite achieving modest metabolic flexibility. Our results highlight the importance of diet composition in mediating the metabolic benefits of short cycles of VLCI.
    DOI:  https://doi.org/10.1038/s41467-021-26654-5
  19. Sarcoidosis Vasc Diffuse Lung Dis. 2021 ;38(3): e2021031
    Frailty and chronic respiratory disease: the need for a multidisciplinary care model.
    Emmanouil K Symvoulakis, Apostolos Kamekis, Elena Drakonaki, Semeli Mastrodemou, Christopher J Ryerson, Katerina Antoniou.
       Background: Frailty is a state of increased vulnerability to various health stressors but little information is summarized about frailty in patients with specific chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and asthma.
    Objective: We aimed to describe the burden of frailty on patients with chronic respiratory disorders and to discuss the need for multidisciplinary care services.
    Methods: PubMed and Cochrane Central databases were systematically reviewed for studies reporting outcomes associated with frailty in COPD, IPF, and asthma. Electronic databases were searched for relevant articles published in English from 2010 up to July 2020. Appraisal was carried out based on the Hierarchy of Evidence Rating System and the GRADE guidelines.
    Results: A total of 31 articles met all inclusion criteria with 24 of them at level IV, 1 at level V, and 6 at level VI. Frailty is likely to negatively affect quality of life and to increase the risk of mortality, especially in elderly with COPD, IPF and asthma. Each disease has a particular effect on the balance between health status, respiratory impairment and frailty. A greater understanding of frailty phenotype across different ages, as well as in a range of long-term conditions, is of great necessity in both clinical and research settings. Limited conformity was observed between different methodologies and nature of chronic diseases studied, leading to a further difficulty to extract homogeneous information.
    Conclusion: Literature shows that frailty is prevalent in COPD, IPF, and asthma, after adjusting for shared risk factors. Our findings suggest that frailty should be approached as an entity per se', in order to assess real mortality risk, alongside respiratory disease severity and the presence of comorbidities. Health care professionals need knowledge, skills and multidisciplinary collaboration to buffer the impact of frailty on everyday practice.
    Keywords:  frailty; health care; quality of life; respiratory diseases
    DOI:  https://doi.org/10.36141/svdld.v38i3.11599
  20. PLoS One. 2021 ;16(11): e0258960
    Charting host-microbe co-metabolism in skin aging and application to metagenomics data.
    Wynand Alkema, Jos Boekhorst, Robyn T Eijlander, Steve Schnittger, Fini De Gruyter, Sabina Lukovac, Kurt Schilling, Guus A M Kortman.
      During aging of human skin, a number of intrinsic and extrinsic factors cause the alteration of the skin's structure, function and cutaneous physiology. Many studies have investigated the influence of the skin microbiome on these alterations, but the molecular mechanisms that dictate the interplay between these factors and the skin microbiome are still not fully understood. To obtain more insight into the connection between the skin microbiome and the human physiological processes involved in skin aging, we performed a systematic study on interconnected pathways of human and bacterial metabolic processes that are known to play a role in skin aging. The bacterial genes in these pathways were subsequently used to create Hidden Markov Models (HMMs), which were applied to screen for presence of defined functionalities in both genomic and metagenomic datasets of skin-associated bacteria. These models were further applied on 16S rRNA gene sequencing data from skin microbiota samples derived from female volunteers of two different age groups (25-28 years ('young') and 59-68 years ('old')). The results show that the main bacterial pathways associated with aging skin are those involved in the production of pigmentation intermediates, fatty acids and ceramides. This study furthermore provides evidence for a relation between skin aging and bacterial enzymes involved in protein glycation. Taken together, the results and insights described in this paper provide new leads for intervening with bacterial processes that are associated with aging of human skin.
    DOI:  https://doi.org/10.1371/journal.pone.0258960
  21. Cell Rep. 2021 Nov 09. pii: S2211-1247(21)01444-3. [Epub ahead of print]37(6): 109965
    Genomic expansion of Aldh1a1 protects beavers against high metabolic aldehydes from lipid oxidation.
    Quanwei Zhang, Gregory Tombline, Julia Ablaeva, Lei Zhang, Xuming Zhou, Zachary Smith, Yang Zhao, Alus M Xiaoli, Zhen Wang, Jhih-Rong Lin, M Reza Jabalameli, Joydeep Mitra, Nha Nguyen, Jan Vijg, Andrei Seluanov, Vadim N Gladyshev, Vera Gorbunova, Zhengdong D Zhang.
      The North American beaver is an exceptionally long-lived and cancer-resistant rodent species. Here, we report the evolutionary changes in its gene coding sequences, copy numbers, and expression. We identify changes that likely increase its ability to detoxify aldehydes, enhance tumor suppression and DNA repair, and alter lipid metabolism, potentially contributing to its longevity and cancer resistance. Hpgd, a tumor suppressor gene, is uniquely duplicated in beavers among rodents, and several genes associated with tumor suppression and longevity are under positive selection in beavers. Lipid metabolism genes show positive selection signals, changes in copy numbers, or altered gene expression in beavers. Aldh1a1, encoding an enzyme for aldehydes detoxification, is particularly notable due to its massive expansion in beavers, which enhances their cellular resistance to ethanol and capacity to metabolize diverse aldehyde substrates from lipid oxidation and their woody diet. We hypothesize that the amplification of Aldh1a1 may contribute to the longevity of beavers.
    Keywords:  beaver genome; gene expansion; gene expression; longevity; positive selection
    DOI:  https://doi.org/10.1016/j.celrep.2021.109965
  22. Eur Heart J. 2021 Nov 07. 42(42): 4296-4297
    An inflammatory ageing clock to detect cardiovascular and other age-related diseases: a new approach to preventive medicine.
    Giovanna Liuzzo, Massimo Volpe.
      
    DOI:  https://doi.org/10.1093/eurheartj/ehab616
  23. Aging (Albany NY). 2021 Nov 11. 13(undefined):
    Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release.
    Steven J Greco, Seda Ayer, Khadidiatou Guiro, Garima Sinha, Robert J Donnelly, Markos H El-Far, Lauren S Sherman, Yannick Kenfack, Sri Harika Pamarthi, Marina Gergues, Oleta A Sandiford, Michael J Schonning, Jean-Pierre Etchegaray, Pranela Rameshwar.
      This study addresses the potential to reverse age-associated morbidity by establishing methods to restore the aged hematopoietic system. Parabiotic animal models indicated that young secretome could restore aged tissues, leading us to establish a heterochronic transwell system with aged mobilized peripheral blood (MPB), co-cultured with young MPB or umbilical cord blood (UCB) cells. Functional studies and omics approaches indicate that the miRNA cargo of microvesicles (MVs) restores the aged hematopoietic system. The in vitro findings were validated in immune deficient (NSG) mice carrying an aged hematopoietic system, improving aged hallmarks such as increased lymphoid:myeloid ratio, decreased inflammation and cellular senescence. Elevated MYC and E2F pathways, and decreased p53 were key to hematopoietic restoration. These processes require four restorative miRs that target the genes for transcription/differentiation, namely PAX and phosphatase PPMIF. These miRs when introduced in aged cells were sufficient to restore the aged hematopoietic system in NSG mice. The aged MPBs were the drivers of their own restoration, as evidenced by the changes from distinct baseline miR profiles in MPBs and UCB to comparable expressions after exposure to aged MPBs. Restorative natural killer cells eliminated dormant breast cancer cells in vivo, indicating the broad relevance of this cellular paradigm - preventing and reversing age-associated disorders such as clearance of early malignancies and enhanced responses to vaccine and infection.
    Keywords:  age; bone marrow; hematopoiesis; miRNA; microvesicles
    DOI:  https://doi.org/10.18632/aging.203689
  24. Nat Rev Cancer. 2021 Nov 11.
    Connecting copper and cancer: from transition metal signalling to metalloplasia.
    Eva J Ge, Ashley I Bush, Angela Casini, Paul A Cobine, Justin R Cross, Gina M DeNicola, Q Ping Dou, Katherine J Franz, Vishal M Gohil, Sanjeev Gupta, Stephen G Kaler, Svetlana Lutsenko, Vivek Mittal, Michael J Petris, Roman Polishchuk, Martina Ralle, Michael L Schilsky, Nicholas K Tonks, Linda T Vahdat, Linda Van Aelst, Dan Xi, Peng Yuan, Donita C Brady, Christopher J Chang.
      Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic research in the chemistry and biology of copper into clinical therapies and diagnostics to exploit copper-dependent disease vulnerabilities. This concept is particularly relevant in cancer, as tumour growth and metastasis have a heightened requirement for this metal nutrient. Indeed, the traditional view of copper as solely an active site metabolic cofactor has been challenged by emerging evidence that copper is also a dynamic signalling metal and metalloallosteric regulator, such as for copper-dependent phosphodiesterase 3B (PDE3B) in lipolysis, mitogen-activated protein kinase kinase 1 (MEK1) and MEK2 in cell growth and proliferation and the kinases ULK1 and ULK2 in autophagy. In this Perspective, we summarize our current understanding of the connection between copper and cancer and explore how challenges in the field could be addressed by using the framework of cuproplasia, which is defined as regulated copper-dependent cell proliferation and is a representative example of a broad range of metalloplasias. Cuproplasia is linked to a diverse array of cellular processes, including mitochondrial respiration, antioxidant defence, redox signalling, kinase signalling, autophagy and protein quality control. Identifying and characterizing new modes of copper-dependent signalling offers translational opportunities that leverage disease vulnerabilities to this metal nutrient.
    DOI:  https://doi.org/10.1038/s41568-021-00417-2
  25. Her Russ Acad Sci. 2021 ;91(5): 587-592
    When Society Ages.
    V G Dobrokhleb.
      Russia is one of the demographically old countries of the world. The process of demographic aging in our country has a number of specific features associated with a change in the age structure of the population, which are determined by the second stage of depopulation; a significant lag in life expectancy indicators not only from economically developed but also from some developing countries; demographic asymmetry by gender; and rather low indicators of healthy life expectancy, which are calculated without accounting for the gender component, and with the burden of diseases dictated by age and accumulated before the age of 65. The current situation increases the relevance of the search for an effective way out of the process of demographic aging, based on strategic approaches to the formation of public health throughout the entire life cycle of a person, including representatives of older age groups.
    Keywords:  age structure of the population; ageism; demographic aging; life expectancy
    DOI:  https://doi.org/10.1134/S1019331621050026
  26. Elife. 2021 Nov 09. pii: e64860. [Epub ahead of print]10
    Evolution of natural lifespan variation and molecular strategies of extended lifespan.
    Alaattin Kaya, Cheryl Zi Jin Phua, Mitchell Lee, Lu Wang, Alexander Tyshkovskiy, Siming Ma, Benjamin Barre, Weiqiang Liu, Benjamin R Harrison, Xiaqing Zhao, Xuming Zhou, Brian M Wasko, Theo K Bammler, Daniel El Promislow, Matt Kaeberlein, Vadim N Gladyshev.
      To understand the genetic basis and selective forces acting on longevity, it is useful to examine lifespan variation among closely related species, or ecologically diverse isolates of the same species, within a controlled environment. In particular, this approach may lead to understanding mechanisms underlying natural variation in lifespan. Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered a wide diversity of replicative lifespan. Phylogenetic analyses pointed to genes and environmental factors that strongly interact to modulate the observed aging patterns. We then identified genetic networks causally associated with natural variation in replicative lifespan across wild yeast isolates, as well as genes, metabolites and pathways, many of which have never been associated with yeast lifespan in laboratory settings. In addition, a combined analysis of lifespan-associated metabolic and transcriptomic changes revealed unique adaptations to interconnected amino acid biosynthesis, glutamate metabolism and mitochondrial function in long-lived strains. Overall, our multi-omic and lifespan analyses across diverse isolates of the same species shows how gene-environment interactions shape cellular processes involved in phenotypic variation such as lifespan.
    Keywords:  S. cerevisiae; genetics; genomics
    DOI:  https://doi.org/10.7554/eLife.64860
  27. Mech Ageing Dev. 2021 Nov 03. pii: S0047-6374(21)00167-6. [Epub ahead of print]200 111595
    Skeletal muscle aging, cellular senescence, and senotherapeutics: Current knowledge and future directions.
    Davis A Englund, Xu Zhang, Zaira Aversa, Nathan K LeBrasseur.
      Cellular senescence is a state of cell cycle arrest induced by several forms of metabolic stress. Senescent cells accumulate with advancing age and have a distinctive phenotype, characterized by profound chromatin alterations and a robust senescence-associated secretory phenotype (SASP) that exerts negative effects on tissue health, both locally and systemically. In preclinical models, pharmacological agents that eliminate senescent cells (senotherapeutics) restore health and youthful properties in multiple tissues. To date, however, very little is understood about the vulnerability of terminally-differentiated skeletal muscle fibers and the resident mononuclear cells that populate the interstitial microenvironment of skeletal muscle to senescence, and their contribution to the onset and progression of skeletal muscle loss and dysfunction with aging. Scientific advances in these areas have the potential to highlight new therapeutic approaches to optimize late-life muscle health. To this end, this review highlights the current evidence and the key questions that need to be addressed to advance the field's understanding of cellular senescence as a mediator of skeletal muscle aging and the potential for emerging senescent cell-targeting therapies to counter age-related deficits in muscle mass, strength, and function.
    Keywords:  Fibroadipogenic progenitor cells; Muscle fiber; Sarcopenia; Satellite cells; Senescence-associated secretory phenotype; Senolytics
    DOI:  https://doi.org/10.1016/j.mad.2021.111595
  28. Indian J Endocrinol Metab. 2021 May-Jun;25(3):25(3): 254-255
    Prevalence of Frailty in Middle-Aged Diabetic Population of Ahmedabad: A Cross-Sectional Study.
    Priyal P Bhatt, Megha S Sheth.
      
    DOI:  https://doi.org/10.4103/ijem.ijem_193_21
  29. Food Sci Nutr. 2021 Nov;9(11): 6406-6420
    Beetroot as a functional food with huge health benefits: Antioxidant, antitumor, physical function, and chronic metabolomics activity.
    Liping Chen, Yuankang Zhu, Zijing Hu, Shengjie Wu, Chengtao Jin.
      Previously, beetroot is mainly consumed as a food additive. In recent years, the beetroot, especially the betalains (betanin) and nitrates it contains, now has received increasing attention for their effective biological activity. Betalains have been proven to eliminate oxidative and nitrative stress by scavenging DPPH, preventing DNA damage, and reducing LDL. It also has been found to exert antitumor activity by inhibiting cell proliferation, angiogenesis, inducing cell apoptosis, and autophagy. In some chronic diseases, nitrate is the main component for lowing blood lipids, glucose, and pressure, while its role in treating hypertension and hyperglycemia has not been clearly stated. Moreover, the intake of nitrate-rich beetroot could enhance athletic performance and attenuate muscle soreness in certain types of exercise. The objective of this review is to provide sufficient evidence for the clarification of health benefits of beetroot, especially in the aspect of biooxidation, neoplastic diseases, some chronic diseases, and energy supplementation.
    Keywords:  beetroot; betanin; biological activity; health benefits; nitrate
    DOI:  https://doi.org/10.1002/fsn3.2577
  30. STAR Protoc. 2021 Dec 17. 2(4): 100927
    Protocol to maintain single functional mouse hematopoietic stem cells in vitro without cell division.
    Miriam Belmonte, David G Kent.
      This protocol details the isolation and in vitro maintenance of single hematopoietic stem cells (HSCs) in the absence of the bone marrow niche. The HSCs do not divide over 7 days and fully retain their long-term functional capacity in transplantation assays. Following hibernation culture, HSCs can be used to study quiescence exit and can be genetically manipulated as single cells prior to division. For complete details on the use and execution of this protocol, please refer to Oedekoven et al. (2021).
    Keywords:  Cell culture; Flow Cytometry/Mass Cytometry; Immunology; Microscopy; Single Cell; Stem Cells
    DOI:  https://doi.org/10.1016/j.xpro.2021.100927
  31. Stroke. 2021 Nov 08. STROKEAHA121037388
    Clonal Hematopoiesis Is Associated With Higher Risk of Stroke.
    NHLBI Trans-Omics for Precision Medicine Program
       BACKGROUND AND PURPOSE: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke.
    METHODS: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes (DNMT3A, TET2, and ASXL1) with any stroke, ischemic stroke, and hemorrhagic stroke.
    RESULTS: CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03-1.27]; P=0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke.
    CONCLUSIONS: CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.
    Keywords:  brain ischemia; cardiovascular diseases; clonal hematopoiesis; humans; prospective studies
    DOI:  https://doi.org/10.1161/STROKEAHA.121.037388
  32. Arch Gerontol Geriatr. 2021 Nov 03. pii: S0167-4943(21)00232-6. [Epub ahead of print]98 104569
    Nutritional status as a mediator between the age-related muscle loss and frailty in community-dwelling older adults.
    Filiz Demirdağ, Esma Nur Kolbaşı, Gözde Balkaya Aykut, Kübra Yıldız Güler, Sadiye Murat, Gülistan Bahat Oztürk, Aytekin Oğuz.
       PURPOSE: The purposes of the study were: a) to investigate the prevalence of sarcopenia, obesity and sarcopenic obesity (SO) in older adults, b) to explore the effect of nutrition as mediator of the association between these entities and frailty.
    MATERIALS AND METHODS: Older adults (≥65 years) were evaluated based on European Working Group on Sarcopenia in Older People criteria for the presence/absence of sarcopenia. Obesity was diagnosed by using Zoico methodology. FRAIL scale was used to evaluate frailty and nutritional status was assessed with Mini Nutritional Assessment (MNA).
    RESULTS: Five-hundred-seventy individuals (68,9% female, mean age 74,41±6,57 years) were included. The prevalence of sarcopenia, obesity and SO were 18,6%, 28,9% and 11,2%, respectively. FRAIL scores were directly affected by having sarcopenia (β: 0.42, 95% CI: (0.21-0.67), p<0.001) and SO (β: 0.31, 95% CI: (0.06-0.59), p:0.015), whereas obesity had no direct effect on FRAIL (β: 0.1, 95% CI: (-0.08-0.3), p:0.26). MNA was a mediator (β: -0.35, 95% CI: (-0.12-(-0.08)), p<0.0001) in both sarcopenic (β: -0.69, 95% CI: (-3.34-(-1.69)), p<0.0001) and SO patients (β: -0.34, 95% CI: (-2.21-(-0.26)), p:0.013), but not in obese group (β: -0.01, 95% CI: (-0.08-0.04). After the Bonferroni corrections,only sarcopenia had an association with frailty with MNA being the mediator.
    CONCLUSION: The findings revealed that the frailty rate was higher in sarcopenia (20,8%) and SO (17,2%) groups than obese (5,5%) group. Frailty was associated with sarcopenia and SO, but not with obesity. Nutritional status was found to be a mediator of the association between age-related muscle loss and frailty To the best of our knowledge, this is the first study to report the mediator of the associations between age-related muscle loss and frailty.
    Keywords:  Frailty; Malnutrition; Obesity; Sarcopenia; Sarcopenic obesity
    DOI:  https://doi.org/10.1016/j.archger.2021.104569
  33. Sci Rep. 2021 Nov 12. 11(1): 22186
    Successful ageing among a national community-dwelling sample of older adults in India in 2017-2018.
    Supa Pengpid, Karl Peltzer.
      This study aimed to determine the prevalence and correlates of successful ageing in older community-dwelling adults in India. The cross-sectional sample included 21,343 individuals (≥ 65 years) from the Longitudinal Ageing Study in India (LASI) Wave 1 in 2017-2018. Successful ageing was assessed utilizing a multidimensional concept, including five components: (1) absence of major illness, (2) free of disability, (3) no major depressive disorder, (4) social engagement and (5) life satisfaction. Overall, 27.2% had successful ageing, including 83.3% had no major diseases, 51.0% free from disability, 91.8% had no major depressive disorder, 73.6% were socially engaged and 74.6% had high life satisfaction. In the adjusted logistic regression analysis, male sex (Adjusted Odds Ratio-AOR 1.40, 95% Confidence Interval-CI 1.21-1.26), married (AOR 1.48, 95% CI 1.22-1.79), having formal education (AOR 1.47, 95% CI 1.23-1.74), high subjective socioeconomic status (AOR 1.61, 95% CI 1.29-2.01), urban residence (AOR 1.42, 95% CI 1.19-1.70), Sikhs (AOR 1.76, 95% CI 1.38-2.24), high physical activity (AOR 1.65, 95% CI 1.38-1.97), and daily Yoga practice (AOR 1.34, 95% CI 1.11-1.61) increased the odds of successful ageing, while increasing age (AOR 0.96, 95% CI 0.94-0.79), poor childhood health (AOR: 0.47, 95% CI 0.29-0.75), and underweight (AOR 0.70, 95% CI 0.61-0.81) decreased the odds of successful ageing. Almost one in three older adults in India were successfully ageing. Factors associated with successful ageing included, male sex, married, having formal education, high subjective socioeconomic status, urban residence, Sikhs, physical activity, Yoga practice, younger age, good childhood health, and not having underweight.
    DOI:  https://doi.org/10.1038/s41598-021-00739-z
  34. Blood. 2021 Nov 11. 138(19): 1790-1792
    Machine learning finds new AML subtypes.
    Daniel Thomas.
      
    DOI:  https://doi.org/10.1182/blood.2021012455
  35. Blood. 2021 Sep 10. pii: blood.2020010447. [Epub ahead of print]
    Syndecan-2 expression enriches for hematopoietic stem cells and regulates stem cell repopulating capacity.
    Christina M Termini, Amara Pang, Michelle Li, Tiancheng Fang, Vivian Y Chang, John P Chute.
      The discovery of novel hematopoietic stem cell (HSC) surface markers can enhance understanding of HSC identity and function. We have discovered a population of primitive bone marrow (BM) HSCs distinguished by their expression of the heparan sulfate proteoglycan, Syndecan-2, which serves as both a marker and regulator of HSC function. Syndecan-2 expression was increased 10-fold in CD150+CD48-CD34-c-Kit+Sca-1+Lineage- cells (long-term - HSCs, LT-HSCs) compared to differentiated hematopoietic cells. Isolation of BM cells based solely on Syndecan-2 surface expression produced a 24-fold enrichment for LT-HSCs, 6-fold enrichment for alpha-catulin+c-kit+ HSCs, and yielded HSCs with superior in vivo repopulating capacity compared to CD150+ cells. Competitive repopulation assays revealed the HSC frequency to be 17-fold higher in Syndecan-2+CD34-KSL cells compared to Syndecan-2-CD34-KSL cells and indistinguishable from CD150+CD34-KSL cells. Syndecan-2 expression also identified nearly all repopulating HSCs within the CD150+CD34-KSL population. Mechanistically, Syndecan-2 regulates HSC repopulating capacity through control of expression of Cdkn1c (p57) and HSC quiescence. Loss of Syndecan-2 expression caused increased HSC cell cycle entry, downregulation of Cdkn1c and loss of HSC long-term - repopulating capacity. Syndecan-2 is a novel marker of HSCs which regulates HSC repopulating capacity via control of HSC quiescence.
    DOI:  https://doi.org/10.1182/blood.2020010447
  36. Trends Cardiovasc Med. 2021 Nov 07. pii: S1050-1738(21)00129-8. [Epub ahead of print]
    Patient-centered care in geriatric cardiology.
    Deena Goldwater, Nanette K Wenger.
      Geriatric cardiology involves providing cardiovascular care to older adults in relation to aging. Although cardiovascular diseases are the most common diseases faced by older adults, they often co-occur with numerous aging-related challenges, such as multimorbidity, frailty, polypharmacy, falls, functional and cognitive impairment, which present challenges to implementing standard disease-based treatment strategies. Faced with these complexities, patient-centered care in geriatric cardiology strives to direct all management toward the achievement of an individual's prioritized health and life goals by employing shared decision-making to align treatment with goals, utilizing stated goals to navigate situations of treatment uncertainty, and pro-actively mitigating aging-related risks. This fundamental change in cardiovascular medicine from disease-centered management to patient-centered goal-directed care is necessary to facilitate wellness, independence, and favorable quality of life outcomes in the older adult population.
    DOI:  https://doi.org/10.1016/j.tcm.2021.11.001
  37. Nutr Hosp. 2021 Nov 10.
    Adherence to the DASH dietary pattern is associated with blood pressure and anthropometric indicators in Mexican adults.
    Xochitl Ponce-Martínez, Eloísa Colín-Ramírez, Sonia Rodríguez-Ramírez, Susana Rivera-Mancía, Raúl Cartas-Rosado, Maite Vallejo-Allende.
       BACKGROUND: adherence to Dietary Approach to Stop Hypertension (DASH) has demonstrated to be effective in lowering blood pressure and other cardiovascular risk markers in different populations, but has never been evaluated in the Mexican population.
    AIM OF THE STUDY: to assess adherence to the DASH dietary pattern by using an adapted DASH adequacy index (DASH-AI), and to evaluate its association with cardiovascular risk markers in an adult Mexican population.
    METHODS: we conducted a cross-sectional analysis of data of 1,490 adults aged 20-50 years. Diet was assessed with a Food Frequency Questionnaire and sodium intake by 24-hour urinary sodium excretion; the DASH-AI score was calculated based on the DASH nutrient targets. Multivariable linear and logistic regression analyses were performed to estimate the association between the DASH-AI score and cardiovascular risk markers (body mass index (BMI), waist circumferences, systolic (SBP) and diastolic blood pressure (DBP), glucose, triglycerides, total cholesterol, and high- and low-density lipoproteins).
    RESULTS: we observed an association of the DASH-AI score with BMI, WC and DBP in the linear (BMI, : -0.55, 95 % CI: -0.77, -0.33; WC, : -1.66, 95 % CI: -2.19, -1.13; DBP, : -0.65, 95 % CI: -1.07, -0.24), and logistic (BMI > 25 kg/m2, OR: 0.82, 95 % CI: 0.74, 0.93; elevated WC, OR: 0.72, 95 % CI: 0.64, 0.81; DBP, OR: 0.83, 95 % CI: 0.72, 0 .95) models.
    CONCLUSION: compliance to the DASH-style diet was inversely associated with BMI, WC and DBP in this Mexican population. Promoting adherence to this dietary pattern in the context of Mexican diet is needed to improve cardiovascular health in this population.
    DOI:  https://doi.org/10.20960/nh.03728
  38. J Clin Med. 2021 Oct 30. pii: 5096. [Epub ahead of print]10(21):
    BCL-2 Expression in AML Patients over 65 Years: Impact on Outcomes across Different Therapeutic Strategies.
    Mario Tiribelli, Angela Michelutti, Margherita Cavallin, Sara Di Giusto, Erica Simeone, Renato Fanin, Daniela Damiani.
      BCL-2 overexpression has been associated with resistance to chemotherapy and reduced survival in acute myeloid leukemia (AML), but few data are available in elderly patients, a subset accounting for majority of AML cases and with dismal prognosis. We retrospectively analyzed 113 AML patients aged ≥65 years treated with 3 + 7 chemotherapy (n = 51) or hypomethylating agents (HMAs) (n = 62), evaluating the role of BCL-2 expression on complete remission (CR) and overall survival (OS). BCL-2 was expressed in 81 patients (72%), more frequently in those with unfavorable cytogenetic-molecular risk. CR was achieved in 34.5% cases, without differences according to BCL-2 expression or induction therapy. In the whole population 1-year OS was 39%, similar in BCL-2+ and BCL-2- cases. In BCL-2 positive patients OS was superior with HMAs (56% vs. 25% with 3 + 7; p = 0.02), while no advantage for HMA was found in BCL-2 negative cases (36% vs. 27% for 3 + 7). Therapy with HMAs was the only factor associated with longer OS in BCL-2+ AML by multivariable analysis. Use of HMAs, possibly in combination with BCL-2 inhibitors, appears to be particularly appealing in BCL2+ AML, where it is associated with superior survival.
    Keywords:  BCL-2; acute myeloid leukemia; elderly; prognosis; survival
    DOI:  https://doi.org/10.3390/jcm10215096
  39. BMC Geriatr. 2021 Nov 12. 21(1): 641
    Assessment of the health status of middle-aged and elderly men with head scale, SF-36, IIEF5, AMS, and IPSS.
    Yi Zhu, Jian-Hui Li, Jing Zhao, Jun-Biao Zheng, Qun-Feng Liang, Xiao-Hua Yu, Shu-Cheng Zhang, Hui-Juan Shi, Wei-Jin Zhou, Qian-Xi Zhu.
       BACKGROUND: Identifying practical and distinguished indicators and influencing factors of male aging may be useful in predicting subsequent aging trends, designing personalized prevention, and improving lifestyle and health.
    METHODS: A cross-sectional, population-based study was performed in Jiashan County, China in 2016. A total of 690 local male residents, aged 40 to 80 years, were eligible for recruitment. Demographic and lifestyle information was collected through structured interviews. A self-designed head scale, the Medical Outcomes Study 36-item Short Form (SF-36), International Index of Erectile Function (IIEF5), Aging Males' Symptoms (AMS), and International Prostate Symptom Score (IPSS) were used. Analysis of variance, local polynomial regression smoothing curves, multiple linear regression, and partial correlation analyses were performed.
    RESULTS: All the scales deteriorated with increasing age (P < 0.01), especially from the age of 60. The most significant changes between adjacent age groups were found in IIEF5 scores (16.7, 43.5 and 39.4%). Income, nutrition, personality and neighborhood relationship had an effect on SF-36 and AMS after adjusting for age (P < 0.01). Furthermore, neighborhood relationship modified the age effect on the head scale score and IIEF5 (P = 0.03); nutrition modified the relationship between age and SF-36 (P < 0.01).
    CONCLUSIONS: Recession of reproductive health may be a distinct predictor of male aging. The associations of social inequalities or personality and health offer potential interventions for men's health in aging. Self-reported scales may limit the precision and more physical fitness tests could be combined for a more precise assessment.
    Keywords:  Aging; Aging males’ symptoms; Biological age; International index of erectile function; International prostate symptom score
    DOI:  https://doi.org/10.1186/s12877-021-02595-y
  40. Sci China Life Sci. 2021 Nov 05.
    Treatment of COVID-19 with MSCs: how does it work?
    Armand Keating.
      
    DOI:  https://doi.org/10.1007/s11427-021-2022-5
  41. Front Pharmacol. 2021 ;12 717570
    Herbal Medicine Compared to Placebo for Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.
    Chan-Young Kwon, Boram Lee, Beom-Joon Lee, Kwan-Il Kim, Hee-Jae Jung.
      Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by irreversible airflow limitation. Many COPD patients use complementary and alternative modalities, including herbal medicines (HMs). This systematic review investigated the effectiveness and safety of HM in managing COPD symptoms compared to placebo. Nine electronic databases were searched to identify relevant randomized controlled trials (RCTs) up to February 12, 2021. The Cochrane risk of bias tool was used to assess the methodological qualities of the included studies. Primary outcomes were lung function parameters and exercise capacity. A meta-analysis was conducted to determine the effect size for homogeneous outcomes. Fourteen studies were included. There was low to very low quality evidence that HM significantly improved forced expiratory volume in 1  s (FEV1) (L), FEV1 (%) and 6-minute walk distance, as well as moderate quality evidence that HM significantly improved forced vital capacity (FVC) (L) compared to placebo. However, according to low quality evidence, there was no significant difference in FEV1/FVC (%) or vital capacity (L) between the groups. Low to moderate evidence suggests that HM has the potential to help improve some respiratory functions, COPD symptoms, and some aspects of quality of life in COPD patients compared to placebo. However, these findings are challenged by the poor methodological quality of the included studies, the heterogeneity of HMs used, and potential publication bias. Therefore, the findings could be significantly influenced by further larger, more rigorous RCTs on this topic. Moreover, it may also be recommended to develop standardized HMs focused on some individual herbs that are frequently used or expected to play an important role in patients with COPD, and to elucidate the underlying mechanisms.
    Keywords:  COPD; chronic bronchitis; east asian traditional medicine; emphysema; systematic review
    DOI:  https://doi.org/10.3389/fphar.2021.717570
  42. Science. 2021 11 12. 374(6569): 825-826
    A dynamic duo.
    Jonathan P Wojciechowski, Molly M Stevens.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.abm3881
  43. Materials (Basel). 2021 Oct 30. pii: 6536. [Epub ahead of print]14(21):
    Aging Resistance of Silica Fume/Styrene-Butadiene-Styrene Composite-Modified Asphalt.
    Jingrong Zhu, Wenyuan Xu.
      The influences of silica fume content and aging on the rheological properties of silica fume/styrene-butadiene-styrene composite-modified asphalts were investigated via rolling thin-film oven test simulations. The asphalts rheological properties before and after aging were measured using three-major-indices, dynamic shear rheology, and bending beam rheometer tests. Fourier transform infrared spectroscopy was used to examine the changes in the functional groups of the asphalt. The silica fume did not chemically react with the modified asphalt, and its original structure was maintained. The aging resistance improved significantly after adding the silica fume. At 6% silica fume content, the relaxation of the asphalt was the highest, indicating that the asphalt had the best low-temperature crack resistance at this mixing proportion. Furthermore, the carbonyl index value of this sample exhibited the smallest increment among all of the samples, and this asphalt sample had the strongest short-term aging resistance. Thus, the optimum silica fume content in the composite-modified asphalt was determined to be 6%. This information may be used to fabricate an asphalt mixture that can improve the service life and aging resistance of pavements.
    Keywords:  aging mechanism; aging resistance; composite-modified asphalt; rheological properties; silica fume
    DOI:  https://doi.org/10.3390/ma14216536
  44. Aging (Albany NY). 2021 Nov 12. 13(undefined):
    Low-protein diet applied as part of combination therapy or stand-alone normalizes lifespan and tumor proliferation in a model of intestinal cancer.
    Alina Proske, Judith Bossen, Jakob von Frieling, Thomas Roeder.
      Tumors of the intestinal tract are among the most common tumor diseases in humans, but, like many other tumor entities, show an unsatisfactory prognosis with a need for effective therapies. To test whether nutritional interventions and a combination with a targeted therapy can effectively cure these cancers, we used the fruit fly Drosophila as a model. In this system, we induced tumors by EGFR overexpression in intestinal stem cells. Limiting the amount of protein in the diet restored life span to that of control animals. In combination with a specific EGFR inhibitor, all major tumor-associated phenotypes could be rescued. This form of treatment was also successful in a real treatment scenario, which means when they started after the full tumor phenotype was expressed. In conclusion, reduced protein administration can be a very promising form of adjuvant cancer therapy.
    Keywords:  Drosophila; EGFR; afatinib; cancer; dietary protein restriction; stem cells
    DOI:  https://doi.org/10.18632/aging.203692
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