bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2021–12–26
twenty-one papers selected by
Ayesh Seneviratne, University of Toronto
  1. Cytosolic Self-DNA-A Potential Source of Chronic Inflammation in Aging.
  2. Associations between frailty trajectories and frailty status and adverse outcomes in community-dwelling older adults.
  3. Social frailty is independently associated with geriatric depression among older adults living in northern Japan: A cross-sectional study of ORANGE registry.
  4. COVID-19 vaccine breakthrough infections.
  5. Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease.
  6. The Potentials of Methylene Blue as an Anti-Aging Drug.
  7. Molecular Basis of Accelerated Aging with Immune Dysfunction-Mediated Inflammation (Inflamm-Aging) in Patients with Systemic Sclerosis.
  8. Temporal Profiling of the Cortical Synaptic Mitochondrial Proteome Identifies Ageing Associated Regulators of Stability.
  9. Transitions in the Cognitive Frailty States in Community-Living Older Adults: A 6-Year Prospective Cohort Study.
  10. Effects of BNT162b2 Covid-19 Vaccine Booster in Long-Term Care Facilities in Israel.
  11. Aging of Podospora anserina Leads to Alterations of OXPHOS and the Induction of Non-Mitochondrial Salvage Pathways.
  12. Age Related Differences in Monocyte Subsets and Cytokine Pattern during Acute COVID-19-A Prospective Observational Longitudinal Study.
  13. Senescent Cells in Cancer: Wanted or Unwanted Citizens.
  14. Is Evidence Supporting the Subtelomere-Telomere Theory of Aging?
  15. Hyponatremia in the frail.
  16. Alpha-Ketoglutarate dietary supplementation to improve health in humans.
  17. Azacitidine and Durvalumab in First-line Treatment of Elderly Patients With Acute Myeloid Leukemia.
  18. [COVID-19 vaccinations: does the mRNA go into breast milk?]
  19. Frailty associations with socioeconomic status, healthcare utilisation and quality of life among older women residing in regional Australia.
  20. Mediterranean Diet a Potential Strategy against SARS-CoV-2 Infection: A Narrative Review.
  21. Age-dependent expression changes of circadian system-related genes reveal a potentially conserved link to aging.
  1. Cells. 2021 Dec 15. pii: 3544. [Epub ahead of print]10(12):
    Cytosolic Self-DNA-A Potential Source of Chronic Inflammation in Aging.
    Mansour Akbari, Daryl P Shanley, Vilhelm A Bohr, Lene Juel Rasmussen.
      Aging is the consequence of a lifelong accumulation of stochastic damage to tissues and cellular components. Advancing age closely associates with elevated markers of innate immunity and low-grade chronic inflammation, probably reflecting steady increasing incidents of cellular and tissue damage over the life course. The DNA sensing cGAS-STING signaling pathway is activated by misplaced cytosolic self-DNA, which then initiates the innate immune responses. Here, we hypothesize that the stochastic release of various forms of DNA from the nucleus and mitochondria, e.g., because of DNA damage, altered nucleus integrity, and mitochondrial damage, can result in chronic activation of inflammatory responses that characterize the aging process. This cytosolic self-DNA-innate immunity axis may perturb tissue homeostasis and function that characterizes human aging and age-associated pathology. Proper techniques and experimental models are available to investigate this axis to develop therapeutic interventions.
    Keywords:  DNA repair; aging; cGAS-STING; cytosolic self-DNA; inflammation; mitochondria
    DOI:  https://doi.org/10.3390/cells10123544
  2. J Cachexia Sarcopenia Muscle. 2021 Dec 23.
    Associations between frailty trajectories and frailty status and adverse outcomes in community-dwelling older adults.
    Alejandro Álvarez-Bustos, Jose Antonio Carnicero-Carreño, Juan Luis Sanchez-Sanchez, Francisco Javier Garcia-Garcia, Cristina Alonso-Bouzón, Leocadio Rodríguez-Mañas.
       BACKGROUND: The association between frailty and adverse outcomes has been clearly defined. Frailty is associated with age, but different frailty evolution patterns might determine the incidence of adverse outcomes at older ages. So far, few observational studies have examined how distinct frailty trajectories could be associated with differences in the risk of adverse events and assessing whether frailty trajectories could define risk of death, hospitalization, worsening, and incident disability better than one-off assessment. Our hypothesis is that prospective increases in frailty levels are associated with higher risk of adverse events compared with subjects that prospectively decreased frailty levels.
    METHODS: Participants' data were taken from the Toledo Study of Healthy Ageing. Frailty was evaluated using the Frailty Trait Scale 5 (FTS5), being 0 the lower (the most robust) and 50 the highest (the frailest) score. FTS5 scores at baseline and follow-up (median 5.04 years) were used to construct frailty trajectories according to group-based trajectory modelling (GBTM). Multivariate Cox proportional hazard and logistic regression models were used to explore associations between frailty status and trajectory membership and the adverse outcomes. Deaths were ascertained through the Spanish National Death Index. Disability was evaluated through the Katz Index. Hospitalization was defined as first admission to Toledo Hospital.
    RESULTS: Nine hundred and seventy-five older adults (mean age 73.14 ± 4.69; 43.38% men) were included. GBTM identified five FTS5 trajectories: worsening from non-frailty (WNF), improving to non-frailty (INF), developing frailty (DF), remaining frail (RF), and increasing frailty (IF). Subjects belonging to trajectories of increasing frailty scores or showing consistently higher frailty levels presented with an increased risk of mortality {DF [hazard ratio (HR), 95% confidence interval (CI)] = 2.01 [1.21-3.32]; RF = 1.92 [1.18-3.12]; IF = 2.67 [1.48-4.81]}, incident [DF (HR, 95% CI) = 2.06 (1.11-3.82); RF = 2.29 (1.30-4.03); IF = 3.55 (1.37-9.24)], and worsening disability [DF (HR, 95% CI) = 2.11 (1.19-3.76); RF = 2.14 (1.26-3.64); IF = 2.21 (1.06-4.62)], compared with subjects prospectively showing decreases in frailty levels or maintaining low FTS5 scores. A secondary result was a significant dose-response relationship between baseline FTS5 score and adverse events.
    CONCLUSIONS: Belonging to trajectories of prospectively increasing/consistently high frailty scores over time are associated with an increased risk of adverse outcomes compared with maintaining low or reducing frailty scores. Our results support the dynamic nature of frailty and the potential benefit of interventions aimed at reducing its levels on relevant and burdensome adverse outcomes.
    Keywords:  Disability; Frailty; Mortality; Older adults; Trajectory modelling
    DOI:  https://doi.org/10.1002/jcsm.12888
  3. Geriatr Gerontol Int. 2021 Dec 22.
    Social frailty is independently associated with geriatric depression among older adults living in northern Japan: A cross-sectional study of ORANGE registry.
    Yu Kume, Ayuto Kodama, Tomoko Takahashi, Sangyoon Lee, Hyuma Makizako, Tsuyosi Ono, Hiroyuki Shimada, Hidetaka Ota.
       AIM: To clarify prevalence of social frailty among older adults living in a rural Japanese community, and factors associated with social frailty status.
    METHODS: In total, 322 adults aged ≥65 years living in a Japanese rural community took part in the study from 2018 to 2020. Social frailty was defined as deficiencies of: (i) living alone; (ii) talking with someone every day; (iii) feeling helpful to friends or family; (iv) going out less frequently compared with last year; and (v) visiting friends sometimes. Social frail status was categorized as robust (0), social prefrail (1), and social frail (≥2), according to the summated score of Makizako's criteria. Multiple logistic regression analysis was applied to clarify factors associated with social frailty status.
    RESULTS: Final samples were classified into 68 persons with social frailty, 98 persons with social prefrailty and 147 persons as robust. We observed the prevalence of social frailty (21.7%) and social prefrailty (31.3%) and the GDS-15 had significantly high scores in the social frail groups. Social frailty was significantly associated with the GDS-15 score (odds ratio, 1.33; 95% CI, 1.19-1.49) and TMT-A (odds ratio, 1.04; 95% CI, 1.01-1.08) and GDS-15 (odds ratio, 1.13; 95% CI, 1.03-1.26) were extracted as independent variables of social prefrail status, with adjustment for demographics, polypharmacy and lifestyle-related diseases.
    CONCLUSIONS: Our results suggest that social frailty tends to be increasing gradually in a Japanese rural area, and social prefrailty might be potentially associated with attentional function, as well as the GDS-15 score. Geriatr Gerontol Int 2021; ••: ••-••.
    Keywords:  cognitive function; geriatric depressive symptom; older adults; social frailty
    DOI:  https://doi.org/10.1111/ggi.14330
  4. Science. 2021 Dec 24. 374(6575): 1561-1562
    COVID-19 vaccine breakthrough infections.
    Ravindra K Gupta, Eric J Topol.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.abl8487
  5. Cells. 2021 Nov 30. pii: 3367. [Epub ahead of print]10(12):
    Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease.
    Seodhna M Lynch, Guangran Guo, David S Gibson, Anthony J Bjourson, Taranjit Singh Rai.
      Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or "sendotypes"), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan.
    Keywords:  COVID-19; SARS-CoV-2; aging; immunosenescence; mortality; sendotypes; senescence; senolytics; severity; vaccination
    DOI:  https://doi.org/10.3390/cells10123367
  6. Cells. 2021 Dec 01. pii: 3379. [Epub ahead of print]10(12):
    The Potentials of Methylene Blue as an Anti-Aging Drug.
    Huijing Xue, Abhirami Thaivalappil, Kan Cao.
      Methylene blue (MB), as the first fully man-made medicine, has a wide range of clinical applications. Apart from its well-known applications in surgical staining, malaria, and methemoglobinemia, the anti-oxidative properties of MB recently brought new attention to this century-old drug. Mitochondrial dysfunction has been observed in systematic aging that affects many different tissues, including the brain and skin. This leads to increaseding oxidative stress and results in downstream phenotypes under age-related conditions. MB can bypass Complex I/III activity in mitochondria and diminish oxidative stress to some degree. This review summarizes the recent studies on the applications of MB in treating age-related conditions, including neurodegeneration, memory loss, skin aging, and a premature aging disease, progeria.
    Keywords:  methylene blue; mitochondria; neurodegeneration; progeria; skin aging
    DOI:  https://doi.org/10.3390/cells10123379
  7. Cells. 2021 Dec 02. pii: 3402. [Epub ahead of print]10(12):
    Molecular Basis of Accelerated Aging with Immune Dysfunction-Mediated Inflammation (Inflamm-Aging) in Patients with Systemic Sclerosis.
    Chieh-Yu Shen, Cheng-Hsun Lu, Cheng-Han Wu, Ko-Jen Li, Yu-Min Kuo, Song-Chou Hsieh, Chia-Li Yu.
      Systemic sclerosis (SSc) is a chronic connective tissue disorder characterized by immune dysregulation, chronic inflammation, vascular endothelial cell dysfunction, and progressive tissue fibrosis of the skin and internal organs. Moreover, increased cancer incidence and accelerated aging are also found. The increased cancer incidence is believed to be a result of chromosome instability. Accelerated cellular senescence has been confirmed by the shortening of telomere length due to increased DNA breakage, abnormal DNA repair response, and telomerase deficiency mediated by enhanced oxidative/nitrative stresses. The immune dysfunctions of SSc patients are manifested by excessive production of proinflammatory cytokines IL-1, IL-6, IL-17, IFN-α, and TNF-α, which can elicit potent tissue inflammation followed by tissue fibrosis. Furthermore, a number of autoantibodies including anti-topoisomerase 1 (anti-TOPO-1), anti-centromere (ACA or anti-CENP-B), anti-RNA polymerase enzyme (anti-RNAP III), anti-ribonuclear proteins (anti-U1, U2, and U11/U12 RNP), anti-nucleolar antigens (anti-Th/T0, anti-NOR90, anti-Ku, anti-RuvBL1/2, and anti-PM/Scl), and anti-telomere-associated proteins were also found. Based on these data, inflamm-aging caused by immune dysfunction-mediated inflammation exists in patients with SSc. Hence, increased cellular senescence is elicited by the interactions among excessive oxidative stress, pro-inflammatory cytokines, and autoantibodies. In the present review, we will discuss in detail the molecular basis of chromosome instability, increased oxidative stress, and functional adaptation by deranged immunome, which are related to inflamm-aging in patients with SSc.
    Keywords:  anti-centromere antibody; anti-topoisomerase 1 antibody; cellular senescence; chromosome instability; immune functional adaptation; inflamm-aging; oxidative stress; proinflammatory cytokines; systemic sclerosis; tissue fibrosis
    DOI:  https://doi.org/10.3390/cells10123402
  8. Cells. 2021 Dec 02. pii: 3403. [Epub ahead of print]10(12):
    Temporal Profiling of the Cortical Synaptic Mitochondrial Proteome Identifies Ageing Associated Regulators of Stability.
    Laura C Graham, Rachel A Kline, Douglas J Lamont, Thomas H Gillingwater, Neil A Mabbott, Paul A Skehel, Thomas M Wishart.
      Synapses are particularly susceptible to the effects of advancing age, and mitochondria have long been implicated as organelles contributing to this compartmental vulnerability. Despite this, the mitochondrial molecular cascades promoting age-dependent synaptic demise remain to be elucidated. Here, we sought to examine how the synaptic mitochondrial proteome (including strongly mitochondrial associated proteins) was dynamically and temporally regulated throughout ageing to determine whether alterations in the expression of individual candidates can influence synaptic stability/morphology. Proteomic profiling of wild-type mouse cortical synaptic and non-synaptic mitochondria across the lifespan revealed significant age-dependent heterogeneity between mitochondrial subpopulations, with aged organelles exhibiting unique protein expression profiles. Recapitulation of aged synaptic mitochondrial protein expression at the Drosophila neuromuscular junction has the propensity to perturb the synaptic architecture, demonstrating that temporal regulation of the mitochondrial proteome may directly modulate the stability of the synapse in vivo.
    Keywords:  aging; mitochondria; neuron; proteomics; synapse
    DOI:  https://doi.org/10.3390/cells10123403
  9. Front Aging Neurosci. 2021 ;13 774268
    Transitions in the Cognitive Frailty States in Community-Living Older Adults: A 6-Year Prospective Cohort Study.
    Huiyu Tang, Huan Zhu, Qianqian Sun, Hai Qin, Shuang Wang.
      Background: Frailty is a multidimensional concept, including physical, cognitive, social, sensorial, psychological, and nutritional phenotypes. Among these phenotypes, cognitive frailty is the most widely investigated, which is related to many adverse health outcomes in older individuals. Whether cognitive frailty is dynamic or how these frail phenotypes interact remains an open issue. We studied the rate of these changes over time and their associated factors in a 6-year follow-up cohort. Methods: A total of 426 Chinese community-living older adults in Dujiangyan aged 65 years or older were involved and followed up in three visits 6 years apart. Frailty and cognitive function were assessed using the FRAIL scale and the Mini-Mental State Examination scale. Demographic information, geriatric syndrome, and social interaction status were studied. Rates of transitions in cognitive frailty states and associated risk factors were studied. We used the stepwise logistic regression model to analyze risk factors. Results: At baseline, 18.8% of participants were only in the physical frailty (PF) or mild cognitive impairment (MCI) group, and 0.09% of participants were in the cognitive frailty group. By the end of 6 years, 62 (14.5%) participants had died, and the rates of only PF or MCI group and cognitive frailty group increased to 36.2 and 3.3%, respectively. Also, 199 (46.7%) participants had deteriorated compared with the baseline. The multivariate regression analysis showed that older (OR = 1.12, 95% CI = 1.07 - 1.16, P < 0.001), smoker (OR = 2.15, 95% CI = 1.37 - 3.39, P = 0.001), poor self-evaluation health status (OR = 1.93, 95% CI = 1.06 - 3.51, P = 0.033), and malnutrition (OR = 2.07, 95% CI = 1.21 - 3.52, P = 0.008) were risk factors for worsening, whereas willing to make new friends (OR = 0.61, 95% CI = 0.38 - 0.96, P = 0.032) was associated with 39% lower chance of deterioration. Conclusion: Cognitive frailty is a dynamically changing state, where transitions may be influenced by multidimensions. Multidimensional monitoring of a wide range of events occurring in aging may be the best way to act early. We hope our study may serve as a starting point for redefining the definition of cognitive frailty by covering different frailty domains.
    Keywords:  cognitive frailty (CF); community-living; elderly; risk factors; transitions
    DOI:  https://doi.org/10.3389/fnagi.2021.774268
  10. N Engl J Med. 2021 Dec 22.
    Effects of BNT162b2 Covid-19 Vaccine Booster in Long-Term Care Facilities in Israel.
    Khitam Muhsen, Nimrod Maimon, Ami Mizrahi, Baruch Varticovschi, Omri Bodenheimer, Udi Gelbshtein, Itamar Grotto, Dani Cohen, Ron Dagan.
      
    DOI:  https://doi.org/10.1056/NEJMc2117385
  11. Cells. 2021 Nov 26. pii: 3319. [Epub ahead of print]10(12):
    Aging of Podospora anserina Leads to Alterations of OXPHOS and the Induction of Non-Mitochondrial Salvage Pathways.
    Verena Warnsmann, Jana Meisterknecht, Ilka Wittig, Heinz D Osiewacz.
      The accumulation of functionally impaired mitochondria is a key event in aging. Previous works with the fungal aging model Podospora anserina demonstrated pronounced age-dependent changes of mitochondrial morphology and ultrastructure, as well as alterations of transcript and protein levels, including individual proteins of the oxidative phosphorylation (OXPHOS). The identified protein changes do not reflect the level of the whole protein complexes as they function in-vivo. In the present study, we investigated in detail the age-dependent changes of assembled mitochondrial protein complexes, using complexome profiling. We observed pronounced age-depen-dent alterations of the OXPHOS complexes, including the loss of mitochondrial respiratory supercomplexes (mtRSCs) and a reduction in the abundance of complex I and complex IV. Additionally, we identified a switch from the standard complex IV-dependent respiration to an alternative respiration during the aging of the P. anserina wild type. Interestingly, we identified proteasome components, as well as endoplasmic reticulum (ER) proteins, for which the recruitment to mitochondria appeared to be increased in the mitochondria of older cultures. Overall, our data demonstrate pronounced age-dependent alterations of the protein complexes involved in energy transduction and suggest the induction of different non-mitochondrial salvage pathways, to counteract the age-dependent mitochondrial impairments which occur during aging.
    Keywords:  OXPHOS; Podospora anserina; aging; complexome profiling
    DOI:  https://doi.org/10.3390/cells10123319
  12. Cells. 2021 Nov 30. pii: 3373. [Epub ahead of print]10(12):
    Age Related Differences in Monocyte Subsets and Cytokine Pattern during Acute COVID-19-A Prospective Observational Longitudinal Study.
    Anita Pirabe, Stefan Heber, Waltraud C Schrottmaier, Anna Schmuckenschlager, Sonja Treiber, David Pereyra, Jonas Santol, Erich Pawelka, Marianna Traugott, Christian Schörgenhofer, Tamara Seitz, Mario Karolyi, Bernd Jilma, Ulrike Resch, Alexander Zoufaly, Alice Assinger.
      The COVID-19 pandemic drastically highlighted the vulnerability of the elderly population towards viral and other infectious threats, illustrating that aging is accompanied by dysregulated immune responses currently summarized in terms like inflammaging and immunoparalysis. To gain a better understanding on the underlying mechanisms of the age-associated risk of adverse outcome in individuals experiencing a SARS-CoV-2 infection, we analyzed the impact of age on circulating monocyte phenotypes, activation markers and inflammatory cytokines including interleukin 6 (IL-6), IL-8 and tumor necrosis factor (TNF) in the context of COVID-19 disease progression and outcome in 110 patients. Our data indicate no age-associated differences in peripheral monocyte counts or subset composition. However, age and outcome are associated with differences in monocyte activation status. Moreover, a distinct cytokine pattern of IL-6, IL-8 and TNF in elderly survivors versus non-survivors, which consolidates over the time of hospitalization, suggests that older patients with adverse outcomes experience an inappropriate immune response, reminiscent of an inflammaging driven immunoparalysis. Our study underscores the value, necessity and importance of longitudinal monitoring in elderly COVID-19 patients, as dynamic changes after symptom onset can be observed, which allow for a differentiated insight into confounding factors that impact the complex pathogenesis following an infection with SARS-CoV-2.
    Keywords:  COVID-19; aging; immunoparalysis; inflammaging; innate immune response; monocytes
    DOI:  https://doi.org/10.3390/cells10123373
  13. Cells. 2021 Nov 26. pii: 3315. [Epub ahead of print]10(12):
    Senescent Cells in Cancer: Wanted or Unwanted Citizens.
    Sven E Niklander, Daniel W Lambert, Keith D Hunter.
      Over recent decades, the field of cellular senescence has attracted considerable attention due to its association with aging, the development of age-related diseases and cancer. Senescent cells are unable to proliferate, as the pathways responsible for initiating the cell cycle are irreversibly inhibited. Nevertheless, senescent cells accumulate in tissues and develop a pro-inflammatory secretome, known as the senescence-associated secretory phenotype (SASP), which can have serious deleterious effects if not properly regulated. There is increasing evidence suggesting senescent cells contribute to different stages of carcinogenesis in different anatomical sites, mainly due to the paracrine effects of the SASP. Thus, a new therapeutic field, known as senotherapeutics, has developed. In this review, we aim to discuss the molecular mechanisms underlying the senescence response and its relationship with cancer development, focusing on the link between senescence-related inflammation and cancer. We will also discuss different approaches to target senescent cells that might be of use for cancer treatment.
    Keywords:  SASP; cancer; carcinogenesis; senescence; senolytics; senomorphics
    DOI:  https://doi.org/10.3390/cells10123315
  14. Biochemistry (Mosc). 2021 Dec;86(12): 1526-1539
    Is Evidence Supporting the Subtelomere-Telomere Theory of Aging?
    Giacinto Libertini, Olga Shubernetskaya, Graziamaria Corbi, Nicola Ferrara.
      The telomere theory tries to explain cellular mechanisms of aging as mainly caused by telomere shortening at each duplication. The subtelomere-telomere theory overcomes various shortcomings of telomere theory by highlighting the essential role of subtelomeric DNA in aging mechanisms. The present work illustrates and deepens the correspondence between assumptions and implications of subtelomere-telomere theory and experimental results. In particular, it is investigated the evidence regarding the relationships between aging and (i) epigenetic modifications; (ii) oxidation and inflammation; (iii) telomere protection; (iv) telomeric heterochromatin hood; (v) gradual cell senescence; (vi) cell senescence; and (vii) organism decline with telomere shortening. The evidence appears broadly in accordance or at least compatible with the description and implications of the subtelomere-telomere theory. In short, phenomena of cellular aging, by which the senescence of the whole organism is determined in various ways, appear substantially dependent on epigenetic modifications regulated by the subtelomere-telomere-telomeric hood-telomerase system. These phenomena appear to be not random, inevitable, and irreversible but rather induced and regulated by genetically determined mechanisms, and modifiable and reversible by appropriate methods. All this supports the thesis that aging is a genetically programmed and regulated phenoptotic phenomenon and is against the opposite thesis of aging as caused by random and inevitable degenerative factors.
    Keywords:  aging; cell senescence; epigenetic changes; gradual cell senescence; phenoptosis; subtelomere; telomere; telomeric heterochromatin hood
    DOI:  https://doi.org/10.1134/S0006297921120026
  15. J Frailty Sarcopenia Falls. 2021 Dec;6(4): 241-245
    Hyponatremia in the frail.
    Nikolaos D Karakousis, Nikolaos A Kostakopoulos.
      As the lifespan increases, special attention has been given to the supportive care needs of the elderly. Frailty is an important issue in third age, since it is related to poor quality of life and mortality. The prevalence of pathological conditions related to sodium levels, specifically hyponatremia, is also present in the elderly. Yet, it is unclear, if hyponatremia and frailty are related to each other. This review summarizes the current state of knowledge regarding hyponatremia and frailty and analyzes five independent studies which searched for an association between those two parameters. As indicated by this study results, hyponatremia consists a risk factor for frailty. This could be explained by an effect of hyponatremia on sarcopenia and on cognitive function, which consist components of frailty. Thus, it is essential to monitor sodium levels in the elderly and to develop related interventions (e.g. using arginine vasopressin antagonists) in order to prevent frailty.
    Keywords:  Cognitive function; Frailty; Hyponatremia; Sarcopenia; Sodium
    DOI:  https://doi.org/10.22540/JFSF-06-241
  16. Trends Endocrinol Metab. 2021 Dec 21. pii: S1043-2760(21)00266-6. [Epub ahead of print]
    Alpha-Ketoglutarate dietary supplementation to improve health in humans.
    Bibek Gyanwali, Zi Xiang Lim, Janjira Soh, Clarissa Lim, Shou Ping Guan, Jorming Goh, Andrea B Maier, Brian K Kennedy.
      Alpha-ketoglutarate (AKG) is an intermediate in the Krebs cycle involved in various metabolic and cellular pathways. As an antioxidant, AKG interferes in nitrogen and ammonia balance, and affects epigenetic and immune regulation. These pleiotropic functions of AKG suggest it may also extend human healthspan. Recent studies in worms and mice support this concept. A few studies published in the 1980s and 1990s in humans suggested the potential benefits of AKG in muscle growth, wound healing, and in promoting faster recovery after surgery. So far there are no recently published studies demonstrating the role of AKG in treating aging and age-related diseases; hence, further clinical studies are required to better understand the role of AKG in humans. This review will discuss the regulatory role of AKG in aging, as well as its potential therapeutic use in humans to treat age-related diseases.
    Keywords:  antioxidant; cellular respiration; citric acid cycle; healthspan; ketoglutaric acids; supplement
    DOI:  https://doi.org/10.1016/j.tem.2021.11.003
  17. Blood Adv. 2021 Dec 21. pii: bloodadvances.2021006138. [Epub ahead of print]
    Azacitidine and Durvalumab in First-line Treatment of Elderly Patients With Acute Myeloid Leukemia.
    Amer M Zeidan, Isaac Wayne Boss, C L Beach, Wilbert B Copeland, Ethan Greene Thompson, Brian A Fox, Vanessa E Hasle, Andrzej Hellmann, David Taussig, Mar Tormo, Maria Teresa Voso, Jamie Cavenagh, Tim O'Connor, Aessandro Previtali, Shelonitda Rose, Lewis R Silverman.
      Evidence suggests that combining immunotherapy with hypomethylating agents may enhance antitumor activity. This phase 2 study investigated the activity and safety of durvalumab, a programmed death ligand 1 (PD-L1) inhibitor, combined with azacitidine for patients aged ≥65 years with acute myeloid leukemia (AML), including analyses to identify biomarkers of treatment response. Patients were randomized to first-line therapy with azacitidine 75 mg/m2 on days 1-7 with (Arm A, n= 64) or without (Arm B, n=65) durvalumab 1500 mg on day 1 every 4 weeks. Overall response rate (complete response [CR] + CR with incomplete blood recovery [CRi]) was similar in both arms (Arm A, 31.3%; Arm B, 35.4%), as were overall survival (A, 13.0 months; B, 14.4 months) and duration of response (A, 24.6 weeks; B, 51.7 weeks; P=0.0765). No new safety signals emerged with combination treatment. The most frequently reported treatment-emergent adverse events were constipation (Arm A, 57.8%; Arm B, 53.2%) and thrombocytopenia (A, 42.2%; B, 45.2%). DNA methylation, mutational status, and PD-L1 expression were not associated with response to treatment. In this study, first-line combination therapy with durvalumab and azacitidine in older patients with AML was feasible, but did not improve clinical efficacy compared with azacitidine alone. ClinicalTrials.gov: NCT02775903.
    DOI:  https://doi.org/10.1182/bloodadvances.2021006138
  18. Monatsschr Kinderheilkd. 2021 Dec 16. 1-2
    [COVID-19 vaccinations: does the mRNA go into breast milk?]
    Reinhold Kerbl.
      
    DOI:  https://doi.org/10.1007/s00112-021-01381-9
  19. J Frailty Sarcopenia Falls. 2021 Dec;6(4): 209-217
    Frailty associations with socioeconomic status, healthcare utilisation and quality of life among older women residing in regional Australia.
    Shi-Jynn Yong, Stella M Gwini, Monica C Tembo, Boon L Ng, Chong Han Low, Robert G Malon, Trisha L Dunning, Julie A Pasco, Mark A Kotowicz.
       Objectives: The health and well-being of older women may be influenced by frailty and low socioeconomic status (SES). This study examined the association between frailty and SES, healthcare utilisation and quality of life (QOL) among older women in regional Australia.
    Methods: Cross-sectional analysis of the Geelong Osteoporosis Study was conducted on 360 women (ages ≥60yr) in the 15-year follow up. Frailty was identified using modified Fried's phenotype. Individual SES measures and healthcare utilisation were documented by questionnaire. Area-based SES was determined by cross-referencing residential addresses with the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). QOL was measured using the Australian World Health Organisation Quality of Life Instrument (WHOQoL-Bref). Multinomial logistic regression was conducted with frailty groupings as outcome.
    Results: Sixty-two (17.2%) participants were frail, 199 (55.3%) pre-frail and 99 (27.5%) robust. Frail participants were older with higher body mass index. Frailty was associated with lower education but not marital status, occupation or IRSAD. Strong associations with frailty were demonstrated for all WHOQoL-Bref domains. Frailty was associated with more primary care doctor visits (p<0.001).
    Conclusions: This population-based study highlights the significant impact of frailty on older women, indicating reduced QOL and increased primary care doctor visits.
    Keywords:  Frailty; Healthcare utilisation; Older women; QOL; SES
    DOI:  https://doi.org/10.22540/JFSF-06-209
  20. Medicina (Kaunas). 2021 Dec 20. pii: 1389. [Epub ahead of print]57(12):
    Mediterranean Diet a Potential Strategy against SARS-CoV-2 Infection: A Narrative Review.
    Yvelise Ferro, Roberta Pujia, Samantha Maurotti, Giada Boragina, Angela Mirarchi, Patrizia Gnagnarella, Elisa Mazza.
      Mediterranean Diet represents the traditional eating habits of populations living around the Mediterranean Sea, and it is associated with a lower risk of overall mortality and cancer incidence and cardiovascular diseases. Severe acute respiratory syndrome coronavirus 2 is a new pandemic, and represents a significant and critical threat to global human health. In this study, we aimed to review the possible effects of Mediterranean Diet against the risk of the coronavirus disease 2019. Several vitamins, minerals, fatty acids, and phytochemicals with their potential anti-COVID-19 activity are presented. Different risk factors may increase or reduce the probability of contracting the disease. Mediterranean Diet has also a positive action on inflammation and immune system and could have a protective effect against severe acute respiratory syndrome coronavirus 2. Further studies are needed to corroborate the benefits of the Mediterranean Diet protective role on infection with SARS-CoV-2.
    Keywords:  COVID-19; Mediterranean diet; SARS-CoV-2; inflammation; nutrition
    DOI:  https://doi.org/10.3390/medicina57121389
  21. Aging (Albany NY). 2021 Dec 19. 13(undefined):
    Age-dependent expression changes of circadian system-related genes reveal a potentially conserved link to aging.
    Emanuel Barth, Akash Srivastava, Diane Wengerodt, Milan Stojiljkovic, Hubertus Axer, Otto W Witte, Alexandra Kretz, Manja Marz.
      The circadian clock system influences the biology of life by establishing circadian rhythms in organisms, tissues, and cells, thus regulating essential biological processes based on the day/night cycle. Circadian rhythms change over a lifetime due to maturation and aging, and disturbances in the control of the circadian system are associated with several age-related pathologies. However, the impact of chronobiology and the circadian system on healthy organ and tissue aging remains largely unknown. Whether aging-related changes of the circadian system's regulation follow a conserved pattern across different species and tissues, hence representing a common driving force of aging, is unclear. Based on a cross-sectional transcriptome analysis covering 329 RNA-Seq libraries, we provide indications that the circadian system is subjected to aging-related gene alterations shared between evolutionarily distinct species, such as Homo sapiens, Mus musculus, Danio rerio, and Nothobranchius furzeri. We discovered differentially expressed genes by comparing tissue-specific transcriptional profiles of mature, aged, and old-age individuals and report on six genes (per2, dec2, cirp, klf10, nfil3, and dbp) of the circadian system, which show conserved aging-related expression patterns in four organs of the species examined. Our results illustrate how the circadian system and aging might influence each other in various tissues over a long lifespan and conceptually complement previous studies tracking short-term diurnal and nocturnal gene expression oscillations.
    Keywords:  RNA-Seq; aging; circadian clock system; circadian rhythm; inter-species comparison; longevity
    DOI:  https://doi.org/10.18632/aging.203788
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