Katsuya Iijima

Bio: Katsuya Iijima is an academic researcher from University of Tokyo. The author has contributed to research in topics: Medicine & Sarcopenia. The author has an hindex of 38, co-authored 149 publications receiving 6003 citations.

Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras–MAPK signaling in human cancer cells

Abstract: The induction of senescence-like growth arrest has emerged as a putative contributor to the anticancer effects of chemotherapeutic agents. Clinical trials are underway to evaluate the efficacy of inhibitors for class I and II histone deacetylases to treat malignancies. However, a potential antiproliferative effect of inhibitor for Sirt1, which is an NAD+-dependent deacetylase and belongs to class III histone deacetylases, has not yet been explored. Here, we show that Sirt1 inhibitor, Sirtinol, induced senescence-like growth arrest characterized by induction of senescence-associated β-galactosidase activity and increased expression of plasminogen activator inhibitor 1 in human breast cancer MCF-7 cells and lung cancer H1299 cells. Sirtinol-induced senescence-like growth arrest was accompanied by impaired activation of mitogen-activated protein kinase (MAPK) pathways, namely, extracellular-regulated protein kinase, c-jun N-terminal kinase and p38 MAPK, in response to epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). Active Ras was reduced in Sirtinol-treated senescent cells compared with untreated cells. However, tyrosine phosphorylation of the receptors for EGF and IGF-I and Akt/PKB activation were unaltered by Sirtinol treatment. These results suggest that inhibitors for Sirt1 may have anticancer potential, and that impaired activation of Ras–MAPK pathway might take part in a senescence-like growth arrest program induced by Sirtinol.

Oral Frailty as a Risk Factor for Physical Frailty and Mortality in Community-Dwelling Elderly.

Abstract: Background Oral health is important for maintaining general health among the elderly. However, a longitudinal association between poor oral health and general health has not been reported. We investigated whether poor oral status can predict physical weakening (physical frailty, sarcopenia, and subsequent disability) and identified the longitudinal impact of the accumulated poor oral health (i.e. oral frailty) on adverse health outcomes, including mortality. Methods A total of 2,011 elderly individuals (aged ≥ 65 years) participated in the baseline survey of the Kashiwa study in 2012. At baseline, 16 oral status measures and covariates such as demographic characteristics were assessed. As outcomes, physical frailty and sarcopenia were assessed at baseline and at follow-up in 2013 and 2014. Physical independence and survival were assessed from 2012 to 2016 at the time of long-term care certification and time of death. Results Poor oral status as determined by the number of natural teeth, chewing ability, articulatory oral motor skill, tongue pressure, and subjective difficulties in eating and swallowing significantly predicted future physical weakening (new onsets of physical frailty, sarcopenia, and disability). Oral frailty was defined as co-existing poor status in ≥3 of the six measures. Sixteen per cent of participants had oral frailty at baseline, which was significantly associated with 2.4-, 2.2-, 2.3-, and 2.2-fold increased risk of physical frailty, sarcopenia, disability, and mortality, respectively. Conclusion Accumulated poor oral status strongly predicted the onset of adverse health outcomes, including mortality among the community-dwelling elderly. Prevention of oral frailty at an earlier stage is essential for healthy aging.

Development of a simple screening test for sarcopenia in older adults

Abstract: Aim To develop a simple screening test to identify older adults at high risk for sarcopenia. Methods We studied 1971 functionally independent, community-dwelling adults aged 65 years or older randomly selected from the resident register of Kashiwa city, Chiba, Japan. Data collection was carried out between September and November 2012. Sarcopenia was defined based on low muscle mass measured by bioimpedance analysis and either low muscle strength characterized by handgrip or low physical performance characterized by slow gait speed. Results The prevalence of sarcopenia was 14.2% in men and 22.1% in women. After the variable selection procedure, the final model to estimate the probability of sarcopenia included three variables: age, grip strength and calf circumference. The area under the receiver operating characteristic curve, a measure of discrimination, of the final model was 0.939 with 95% confidence interval (CI) of 0.918–0.958 for men, and 0.909 with 95% CI of 0.887–0.931 for women. We created a score chart for each sex based on the final model. When the sum of sensitivity and specificity was maximized, sensitivity, specificity, and positive and negative predictive values for sarcopenia were 84.9%, 88.2%, 54.4%, and 97.2% for men, 75.5%, 92.0%, 72.8%, and 93.0% for women, respectively. Conclusions The presence of sarcopenia could be detected using three easily obtainable variables with high accuracy. The screening test we developed could help identify functionally independent older adults with sarcopenia who are good candidates for intervention. Geriatr Gerontol Int 2014; 14 (Suppl. 1): 93–101.

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Sarcopenia: Revised European consensus on definition and diagnosis

Abstract: Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

Dietary (Poly)phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects Against Chronic Diseases

Abstract: Human intervention trials have provided evidence for protective effects of various (poly)phenol-rich foods against chronic disease, including cardiovascular disease, neurodegeneration, and cancer. While there are considerable data suggesting benefits of (poly)phenol intake, conclusions regarding their preventive potential remain unresolved due to several limitations in existing studies. Bioactivity investigations using cell lines have made an extensive use of both (poly)phenolic aglycones and sugar conjugates, these being the typical forms that exist in planta, at concentrations in the low-μM-to-mM range. However, after ingestion, dietary (poly)phenolics appear in the circulatory system not as the parent compounds, but as phase II metabolites, and their presence in plasma after dietary intake rarely exceeds nM concentrations. Substantial quantities of both the parent compounds and their metabolites pass to the colon where they are degraded by the action of the local microbiota, giving rise principally to small phenolic acid and aromatic catabolites that are absorbed into the circulatory system. This comprehensive review describes the different groups of compounds that have been reported to be involved in human nutrition, their fate in the body as they pass through the gastrointestinal tract and are absorbed into the circulatory system, the evidence of their impact on human chronic diseases, and the possible mechanisms of action through which (poly)phenol metabolites and catabolites may exert these protective actions. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes.