Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). ...HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.
Obesity is a risk factor for disability, but risk of specific adipose depots is not completely understood.
We investigated associations between mobility limitation, performance, and the following ...adipose measures: body mass index (BMI) and areas and densities of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) in older adults.
This was a prospective population-based study of men (n = 1459) and women (n = 1552) initially aged 70–79 y and free from mobility limitation. BMI was determined from measured height and weight. Adipose tissue area and density in Hounsfield units were measured in the thigh and abdomen by using computed tomography. Mobility limitation was defined as 2 consecutive reports of difficulty walking one-quarter mile or climbing 10 steps during semiannual assessments over 13 y. Poor performance was defined as a gait speed <1 m/s after 9 y of follow-up (n = 1542).
In models adjusted for disability risk factors, BMI, and areas of VAT, abdominal SAT, and IMAT were positively associated with mobility limitation in men and women. In women, thigh SAT area was positively associated with mobility limitation risk, whereas VAT density was inversely associated. Associations were similar for poor performance. BMI and thigh IMAT area (independent of BMI) were particularly strong indicators of incident mobility limitation and poor performance. For example, in women, the HR (95% CI) and OR (95% CI) associated with an SD increment in BMI for mobility limitation and poor performance were 1.31 (1.21, 1.42) and 1.41 (1.13, 1.76), respectively. In men, the HR (95% CI) and OR (95% CI) associated with an SD increment in thigh IMAT for mobility limitation and poor performance were 1.37 (1.27, 1.47) and 1.54 (1.18, 2.02), respectively.
Even into old age, higher BMI is associated with mobility limitation and poor performance. The amount of adipose tissue in abdominal and thigh depots may also convey risk beyond BMI.
Data on the protein requirements of elderly adults are limited, because it is impractical to conduct repeated nitrogen balance protocols in these vulnerable humans.
This study was designed to ...determine the dietary protein requirement of elderly women by using the recently developed minimally invasive indicator amino acid oxidation (IAAO) technique.
Six white women aged 80–87 y mean ± SEM: 82 ± 1 y and body mass index (in kg/m2) 26 ± 2 completed a 3-d protocol 7 times. Each woman consumed an adaptation diet for 2 d and on day 3 consumed a complete test diet with a crystalline amino acid mixture containing 1 of 7 protein intakes (0.1, 0.3, 0.6, 0.9, 1.2, 1.5, or 1.8 g · kg−1 · d−1) tested randomly. A group-based protein requirement was assessed by using a nonlinear mixed model of protein intake and l-1-13Cphenylalanine oxidation. The breakpoint, at which there was no further decline in the rate of appearance of 13C in the breath, was used as an index of the mean protein requirement.
The mean protein requirement (95% CI) was 0.85 (0.60, 1.09) g · kg−1 · d−1. This requirement is 29% higher than the current Estimated Average Requirement (EAR) for adults of 0.66 g · kg−1 · d−1 based on the nitrogen balance technique, although the 95% CI includes the current EAR. The corresponding adequate protein allowance of 1.15 (0.77, 1.54) g · kg−1 · d−1 is 44% higher, although the 95% CI includes the Recommended Dietary Allowance (RDA) of 0.80 g · kg−1 · d−1.
Notwithstanding uncertainty about the validity of the use of the IAAO technique to assess protein requirements, the results of this study with octogenarian women suggest that the current EAR and RDA for elderly women may be underestimated. The limitations of this short-term, noninvasive method underscore the need for new research that uses alternative experimental designs and measuring physiologic, morphologic, and health-related outcomes. This trial was registered at clinicaltrials.gov as NCT01193946.
Lesbian, gay, bisexual, and transgender (LGBT) people are a health disparate population as identified in Healthy People 2020. Yet, there has been limited attention to how LGBT older adults maintain ...successful aging despite the adversity they face. Utilizing a Resilience Framework, this study investigates the relationship between physical and mental health-related quality of life (QOL) and covariates by age group.
A cross-sectional survey of LGBT adults aged 50 and older (N = 2,560) was conducted by Caring and Aging with Pride: The National Health, Aging, and Sexuality Study via collaborations with 11 sites across the U.S. Linear regression analyses tested specified relationships and moderating effects of age groups (aged 50-64; 65-79; 80 and older).
Physical and mental health QOL were negatively associated with discrimination and chronic conditions and positively with social support, social network size, physical and leisure activities, substance nonuse, employment, income, and being male when controlling for age and other covariates. Mental health QOL was also positively associated with positive sense of sexual identity and negatively with sexual identity disclosure. Important differences by age group emerged and for the old-old age group the influence of discrimination was particularly salient.
This is the first study to examine physical and mental health QOL, as an indicator of successful aging, among LGBT older adults. An understanding of the configuration of resources and risks by age group is important for the development of aging and health initiatives tailored for this growing population.
The protective effects of antioxidant vitamins on hearing loss are well established in animal studies but in few human studies. Recent animal studies suggest that magnesium intake along with ...antioxidants may act in synergy to prevent hearing loss.
We examined associations between intake of antioxidant vitamins (daily β-carotene and vitamins C and E) and magnesium and hearing thresholds and explored their joint effects in US adults.
We analyzed cross-sectional data from 2592 participants aged 20–69 y from NHANES 2001–2004. Hearing thresholds as pure tone averages (PTAs) at speech (0.5, 1, 2, and 4 kHz) and high frequencies (3, 4, and 6 kHz) were computed.
When examined individually, modeled as quartiles, and after adjustment for potential confounders, higher intakes of β-carotene, vitamin C, and magnesium were associated with lower (better) PTAs at both speech and high frequencies. High intakes of β-carotene or vitamin C combined with high magnesium compared with low intakes of both nutrients were significantly associated with lower (better) PTAs at high frequencies (−14.82%; 95% CI: −20.50% to −8.74% for β-carotene + magnesium and −10.72%; 95% CI: −16.57% to −4.45% for vitamin C + magnesium). The estimated joint effects were borderline significantly larger than the sums of the individual effects high β-carotene/low magnesium (−4.98%) and low β-carotene/high magnesium (−0.80%), P-interaction = 0.08; high vitamin C/low magnesium (−1.33%) and low vitamin C/high magnesium (2.13%), P-interaction = 0.09.
Dietary intakes of antioxidants and magnesium are associated with lower risks of hearing loss.
Aging and Lung Disease Cho, Soo Jung; Stout-Delgado, Heather W
Annual review of physiology,
02/2020, Letnik:
82
Journal Article
Recenzirano
Odprti dostop
People worldwide are living longer, and it is estimated that by 2050, the proportion of the world's population over 60 years of age will nearly double. Natural lung aging is associated with molecular ...and physiological changes that cause alterations in lung function, diminished pulmonary remodeling and regenerative capacity, and increased susceptibility to acute and chronic lung diseases. As the aging population rapidly grows, it is essential to examine how alterations in cellular function and cell-to-cell interactions of pulmonary resident cells and systemic immune cells contribute to a higher risk of increased susceptibility to infection and development of chronic diseases, such as chronic obstructive pulmonary disease and interstitial pulmonary fibrosis. This review provides an overview of physiological, structural, and cellular changes in the aging lung and immune system that facilitate the development and progression of disease.
Abstract
Biological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of 8 DNA-methylation (DNAm) and blood-chemistry ...quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the 2016 wave of the Health and Retirement Study (n = 9,005). We quantified biological aging from 4 DNAm “clocks” (Horvath, Hannum, PhenoAge, and GrimAge clock), a DNAm pace-of-aging measure (DunedinPoAm), and 3 blood-chemistry measures (PhenoAge, Klemera-Doubal method biological age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical performance tests, self-reported limitations in activities of daily living, and physician-diagnosed chronic diseases, self-rated health, and survival. DNAm and blood-chemistry quantifications of biological aging were moderately correlated (Pearson’s r = 0.1–0.4). The GrimAge clock, DunedinPoAm, and all 3 blood-chemistry measures were associated with healthspan characteristics (e.g., mortality effect-size hazard ratios were 1.71–2.32 per standard deviation of biological aging) and showed evidence of more advanced/faster biological aging in Black participants than in White participants (Cohen’s d = 0.4–0.5). These measures accounted for 13%–95% of Black-White differences in healthspan-related characteristics. Findings suggest that reducing disparities in biological aging can contribute to building health equity.
To facilitate the process of aging healthily and prevent age-related health problems, efforts to properly understand aging mechanisms and develop effective and affordable anti-aging interventions are ...deemed necessary. Systemic administration of
d
-galactose has been established to artificially induce senescence in vitro and in vivo as well as for anti-aging therapeutic interventions studies. The aim of this article is to comprehensively discuss the use of
d
-galactose to generate a model of accelerated aging and its possible underlying mechanisms involved in different tissues/organs.
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