APC

Adenomatous polyposis coli protein (Protein APC) (Deleted in polyposis 2.5) [DP2.5]

Publications

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Differences between blacks and whites in well-being, beliefs, emotional states, behaviors and survival, 1978-2014.

PubMed

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Material well-being, beliefs, and emotional states are believed to influence one's health and longevity. In this paper, we explore racial differences in self-rated health, happiness, trust in others, feeling that society is fair, believing in God, frequency of sexual intercourse, educational attainment, and percent in poverty and their association with mortality. Age-period-cohort (APC) study. Using data from the 1978-2014 General Social Survey-National Death Index (GSS-NDI), we conducted APC analyses using generalized linear models to quantify the temporal trends of racial differences in our selected measures of well-being, beliefs, and emotional states. We then conducted APC survival analysis using mixed-effects Cox proportional hazard models to quantify the temporal trends of racial differences in survival after removing the effects of racial differences in our selected measures. For whites, the decline in happiness was steeper than for blacks despite an increase in high school graduation rates among whites relative to blacks over the entire period, 1978-2010. Self-rated health increased in whites relative to blacks from 1978 through 1989 but underwent a relative decline thereafter. After adjusting for age, sex, period effects, and birth cohort effects, whites, overall, had higher rates of self-rated health (odds ratio [OR] = 1.88; 95% confidence interval [CI] = 1.63, 2.16), happiness (OR = 2.05; 1.77, 2.36), and high school graduation (OR = 2.88; 2.34, 3.53) compared with blacks. Self-rated health, happiness, and high school graduation also mediated racial differences in survival over time. We showed that some racial differences in survival could be partly mitigated by eliminating racial differences in health, happiness, and educational attainment. Future research is needed to analyze longitudinal clusters and identify causal mechanisms by which social, behavioral, and economic interventions can reduce survival differences.

MeSH Terms

• Adult
• African Americans
• Aged
• Behavior
• Cohort Studies
• Emotions
• European Continental Ancestry Group
• Female
• Hispanic Americans
• Humans
• Longevity
• Male
• Middle Aged
• Socioeconomic Factors
• Survival Analysis
• United States

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Wnt-induced, TRP53-mediated Cell Cycle Arrest of Precursors Underlies Interstitial Cell of Cajal Depletion During Aging.

PubMed

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Gastric dysfunction in the elderly may cause reduced food intake, frailty, and increased mortality. The pacemaker and neuromodulator cells interstitial cells of Cajal (ICC) decline with age in humans, and their loss contributes to gastric dysfunction in progeric klotho mice hypomorphic for the anti-aging Klotho protein. The mechanisms of ICC depletion remain unclear. Klotho attenuates Wnt (wingless-type MMTV integration site) signaling. Here, we examined whether unopposed Wnt signaling could underlie aging-associated ICC loss by up-regulating transformation related protein TRP53 in ICC stem cells (ICC-SC). Mice aged 1-107 weeks, klotho mice, APC mice with overactive Wnt signaling, mouse ICC-SC, and human gastric smooth muscles were studied by RNA sequencing, reverse transcription-polymerase chain reaction, immunoblots, immunofluorescence, histochemistry, flow cytometry, and methyltetrazolium, ethynyl/bromodeoxyuridine incorporation, and ex-vivo gastric compliance assays. Cells were manipulated pharmacologically and by gene overexpression and RNA interference. The klotho and aged mice showed similar ICC loss and impaired gastric compliance. ICC-SC decline preceded ICC depletion. Canonical Wnt signaling and TRP53 increased in gastric muscles of klotho and aged mice and middle-aged humans. Overstimulated canonical Wnt signaling increased DNA damage response and TRP53 and reduced ICC-SC self-renewal and gastric ICC. TRP53 induction persistently inhibited G /S and G /M cell cycle phase transitions without activating apoptosis, autophagy, cellular quiescence, or canonical markers/mediators of senescence. G /S block reflected increased cyclin-dependent kinase inhibitor 1B and reduced cyclin D1 from reduced extracellular signal-regulated kinase activity. Increased Wnt signaling causes age-related ICC loss by up-regulating TRP53, which induces persistent ICC-SC cell cycle arrest without up-regulating canonical senescence markers.

Keywords

• Compliance
• Senescence
• Stem Cell

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Burden of musculoskeletal disorders in Iran during 1990-2017: estimates from the Global Burden of Disease Study 2017.

PubMed

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Musculoskeletal diseases (MSDs) are the leading cause of disability and facing them demands updated reports on their burden for efficient policymaking. We showed Iran had the highest female-to-male ratio and highest increase in the burden of musculoskeletal diseases, in the past three decades, worldwide. We further confirmed the role of population aging as the main cause. MSDs comprise most of the top causes of years lived with disability (YLDs) worldwide and are rapidly increasing in lower- and middle-income countries. Here, we present disability and mortality due to MSDs in Iran at the national level from 1990 to 2017. We used Global Burden of Disease (GBD) 2017 Study data and standard methodology and presented the burden of MSDs in rates of years of life lost (YLLs), YLDs, and disability-adjusted life years (DALYs) during 1990-2017, for population aged ≥ 5 years old. We further explored attributable risk factors and decomposed the changing trend in DALYs to assess underlying causes. In Iran, MSDs were responsible for 1.82 million (95%uncertainty interval [UI] 1.3-2.4) DALYs, in 2017. During the past 28 years, with 1.75% annualized percentage change (APC), Iran had the highest percentage increase in the all-ages MSD DALYs rate worldwide, while the age-standardized DALYs APC was negligible. Low back pain was the greatest contributor to DALYs and caused 4.5% of total DALYs. The female population is experiencing considerably higher burden of MSDs, with 115% and 48% higher all-ages YLLs and YLDs rates per 100,000, respectively (YLLs 28.7; YLDs 2629.1), than males (YLLs 13.2; YLDs 1766.1). However, due to wide UIs, difference was not significant. Only 17.6% of MSD YLDs are attributable to assessed risk factors. Despite that MSDs are rising as an important cause of disability in Iran, these conditions are not sufficiently addressed in health policies. There is urgent need for cross-sectoral engagement, especially addressing the MSDs in females.

MeSH Terms

• Female
• Global Burden of Disease
• Global Health
• Humans
• Iran
• Life Expectancy
• Male
• Musculoskeletal Diseases
• Quality-Adjusted Life Years

Keywords

• Burden
• DALY
• Decomposition
• Global burden of diseases
• Iran
• Musculoskeletal diseases

{{medline-entry |title=Fall-related mortality trends in older Japanese adults aged ≥65 years: a nationwide observational study. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31831549 |abstract=Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016. We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare. The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women. Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required. |mesh-terms=* Accidental Falls

• Aged
• Aged, 80 and over
• Female
• Geriatrics
• Health Policy
• Health Services Needs and Demand
• Humans
• Japan
• Male
• Mortality
• Public Health

|keywords=* adult intensive