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Complement factor D precursor (EC (Adipsin) (C3 convertase activator) (Properdin factor D) [DF] [PFD]


Associations of Sedentary and Physically-Active Behaviors With Cognitive-Function Decline in Community-Dwelling Older Adults: Compositional Data Analysis From the NEIGE Study.

Physical activity can help to protect against cognitive decline in older adults. However, little is known about the potential combined relationships of time spent in sedentary behavior (SB), light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) with indices of cognitive health. We examined the cross-sectional associations of objectively-determined sedentary and physically-active behaviors with an indicator of cognitive function decline (CFD) in older adults. A randomly-recruited sample of 511 Japanese older adults (47% male; aged 65-84 years) wore a tri-axial accelerometer for 7 consecutive days in 2017. Cognitive function was assessed by interviewers using the Japanese version of Mini-Mental State Examination, with a score of ≤23 indicating CFD. Associations of sedentary and physically-active behaviors with CFD were examined using a compositional logistic regression analysis based on isometric log-ratio transformations of time use, adjusting for potential confounders. Forty one (9.4%) of the participants had an indication of CFD. Activity compositions differed significantly between CFD and normal cognitive function (NCF); the proportion of time spent in MVPA was 39.1% lower, relative to the overall mean composition in those with CFD, and was 5.3% higher in those with NCF. There was a significant beneficial association of having a higher proportion of MVPA relative to other activities with CFD. LPA and SB were not associated with CFD when models were corrected for time spent in all activity behaviors. Larger relative contribution of MVPA was favorably associated with an indicator of CFD in older adults.


  • accelerometry
  • aging
  • exercise
  • neurocognitive disorders
  • sedentary lifestyle

Senescent dermal fibroblasts negatively influence fibroblast extracellular matrix-related gene expression partly via secretion of complement factor D.

Aging is associated with a decrease of extracellular matrix and an increase of senescent cells in the dermal layer. Here, to examine whether and how senescent cells are involved in aging-related deterioration of the dermal layer, we cocultured dermal young fibroblasts (low-passage number) with senescent cells (high-passage number) in Transwells, in which the two cell types are separated by a semipermeable membrane. Young fibroblasts in coculture showed decreased collagen type I alpha 1 chain and elastin gene expression, and increased matrix metalloproteinase 1 (MMP1) gene expression. To identify causative factors, we compared gene expression of young and senescent cells and selected candidate secretory factors whose expression was increased by ≥2.5 in senescent fibroblasts. Then, we used siRNAs to knock down each of the 11 candidate genes in senescent fibroblasts in the coculture system. Knockdown of complement factor D (CFD) in senescent fibroblasts significantly reduced the increase of MMP1 in the cocultured young fibroblasts. In monocultures, treatment of young fibroblasts with CFD resulted in increased MMP1 gene expression, while knockdown of CFD in senescent fibroblasts decreased MMP1 gene expression. In addition, production of CFD was increased in culture medium of untreated senescent fibroblasts. Furthermore, CFD gene and protein expression were increased in the dermal layer of skin specimens from aged subjects (>70 years old), compared to young subjects (<20 years old). Overall, these results suggest that senescent cells negatively influence matrix production and promote degradation of nearby fibroblasts in the dermal layer, in part through secretion of CFD.

MeSH Terms

  • Cell Proliferation
  • Cellular Senescence
  • Coculture Techniques
  • Collagen Type I
  • Complement Factor D
  • Diffusion Chambers, Culture
  • Elastin
  • Extracellular Matrix
  • Fibroblasts
  • Gene Expression Regulation
  • Humans
  • Matrix Metalloproteinase 1
  • Primary Cell Culture
  • RNA, Small Interfering
  • Signal Transduction


  • CFD
  • MMP1
  • SASP
  • fibroblast
  • senescence

New horizons in the compression of functional decline.

Population ageing, which has come about through the combination of increases in life expectancy, larger post-war cohorts reaching older age and reductions in fertility, is challenging societies and particularly health and care providers, worldwide. In Europe, the USA and Japan, there have been increases in years spent with disability and dependency. The majority of such research, as well as professional health and social care practice, measures loss of functional capability or need for social care, by aggregate disability scores, based around activities of daily living and instrumental activities of daily living. Although useful for defining whether an individual has passed a threshold, aggregate scores obscure how functional decline unfolds, and therefore where early intervention might improve intrinsic capacity and reverse or slow down decline, or maintain function. We propose a framework, the compression of functional decline (CFD), based on the latest understanding of the hierarchy of age-related functional decline, which has the potential to (i) help people understand how to live better for longer, (ii) allow the various stakeholders to be able to measure, at a population level, whether that is happening and (iii) identify which interventions are most effective at which stages. CFD is coherent with the World Health Organisation's Healthy Ageing model and is more easily understood by stakeholders and older people themselves, than current indicators such as frailty. CFD thus provides a realistic view of age-related functional decline in the context of modifiable behaviour to counter widespread public misconceptions about ageing and inform improvements.

MeSH Terms

  • Activities of Daily Living
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Dependency, Psychological
  • Disability Evaluation
  • Geriatric Assessment
  • Geriatrics
  • Healthy Aging
  • Humans
  • Longevity
  • Predictive Value of Tests
  • Risk Factors

Precocial development of locomotor performance in a ground-dwelling bird (Alectoris chukar): negotiating a three-dimensional terrestrial environment.

Developing animals are particularly vulnerable to predation. Hence, precocial young of many taxa develop predator escape performance that rivals that of adults. Ontogenetically unique among vertebrates, birds transition from hind limb to forelimb dependence for escape behaviours, so developmental investment for immediate gains in running performance may impair flight performance later. Here, in a three-dimensional kinematic study of developing birds performing pre-flight flapping locomotor behaviours, wing-assisted incline running (WAIR) and a newly described behaviour, controlled flapping descent (CFD), we define three stages of locomotor ontogeny in a model gallinaceous bird (Alectoris chukar). In stage I (1-7 days post-hatching (dph)) birds crawl quadrupedally during ascents, and their flapping fails to reduce their acceleration during aerial descents. Stage II (8-19 dph) birds use symmetric wing beats during WAIR, and in CFD significantly reduce acceleration while controlling body pitch to land on their feet. In stage III (20 dph to adults), birds are capable of vertical WAIR and level-powered flight. In contrast to altricial species, which first fly when nearly at adult mass, we show that in a precocial bird the major requirements for flight (i.e. high power output, wing control and wing size) convene by around 8 dph (at ca 5% of adult mass) and yield significant gains in escape performance: immature chukars can fly by 20 dph, at only about 12 per cent of adult mass.

MeSH Terms

  • Aging
  • Animals
  • Biomechanical Phenomena
  • Body Weight
  • Flight, Animal
  • Galliformes
  • Motor Activity
  • Running
  • Wings, Animal

Capillarisation and fibre types in hypertrophied m. plantaris in rats of various ages.

Influences of age, overload obtained through denervation of synergists, and training on the capillarisation of the m. plantaris were compared in 5-, 13- and 25-month-old rats in relation to different fibre types. Overload resulted in about 30% hypertrophy in each age group. Age effects were significant only in the deep (more oxidative) region of the muscle. From 5 to 13 months, the percentage of FOG fibres increased at the expense of FG fibres, while the fibre cross-sectional areas (FCSA) of each fibre type increased. From 13 to 25 months, the FCSA of FG fibres decreased, as did the local capillary-to-fibre ratio (LCFR) of each fibre type, indicating capillary loss and a declined capillary density for each fibre type (CFD). Overload effects were identical for both the superficial (more glycolytic) and the deep region for each age group. With overload, FCSA and LCFR of each fibre type increased, while CFD decreased, indicating that capillary proliferation occurred with overload, even at old age, although lagging behind increases in FCSAs. Training showed minor effects.

MeSH Terms

  • Aging
  • Animals
  • Capillaries
  • Female
  • Hindlimb
  • Hypertrophy
  • Muscles
  • Physical Conditioning, Animal
  • Rats
  • Rats, Wistar

Effects of the type of dietary fat at two levels of vitamin E in Wistar male rats during development and aging. I. Life span, serum biochemical parameters and pathological changes.

This experiment was designed to study in rats the implications of the dietary type of fat at two levels of vitamin E on the life span as well as on several biochemical and anatomopathological age-related changes. For this purpose, six different isoenergetic diets containing 15% coconut oil (SFD), safflower oil (UFD) or a combination of both (CFD) with 2 or 200 mg% of dl-alpha-tocopherol were offered ad libitum to outbred Wistar male rats from weaning to senescence. The results indicated that up to 9--12 months the body weights of rats consuming the CFD or the UFD increased generally faster than those fed the SFD, and that all rats developed moderate degrees of obesity. Age-dependent changes in organ weights (kidneys, testes, spleen, brain, liver and heart) were unaffected by diet. Serum levels of vitamin E generally reflected the corresponding dietary levels, but were also influenced by the type of dietary fat. Serum cholesterol levels were not significantly affected by the type of diet or by age. Only transient hypotriglyceridemic and hypophospholipidemic effects of the UFD were observed and, while the levels of triglycerides decreased with age up to the 18th month followed by an increase at 24 months, the levels of serum phospholipids remained unchanged. Neither diet nor age modified the serum albumin/globulin ratios. While no differences in maximum life span were found between dietary groups, the 50% survival time of rats fed the UFD at high level of vitamin E was significantly longer than in all the other groups. This beneficial effect was related to postponement of the onset and reduction of incidence of malignant neoplasms, but was apparently not related to any particular influence on the incidence or severity of chronic nephropathy which practically developed in all rats. Various neoplastic, degenerative and inflammatory diseases encountered in rats dying during the course of the experiment were tabulated and compared with similar findings reported by others in different strains of rats. Pituitary and adrenocortical adenomas as well as adrenocortical and renal carcinomas were the most frequent tumors found in this study. All the pathological changes provided useful baseline information for the evaluation of data presented in this and subsequent communications of this series of studies.

MeSH Terms

  • Aging
  • Animals
  • Body Weight
  • Cardiovascular Diseases
  • Central Nervous System Diseases
  • Cholesterol
  • Dietary Fats
  • Digestive System Diseases
  • Energy Intake
  • Eye Diseases
  • Life Expectancy
  • Male
  • Neoplasms
  • Organ Size
  • Phospholipids
  • Rats
  • Respiratory System
  • Serum Albumin
  • Skin Diseases
  • Tissue Distribution
  • Triglycerides
  • Urogenital System
  • Vitamin E

[Physical properties of the aorta and left ventricular geometry evaluated by Doppler echocardiography in normal subjects].

In 45 normotensive subjects (21-84 years) we simultaneously measured: 1) arterial pressure (AP) according to guidelines of the World-health-organization; 2) left ventricular (LV) wall thickness (WT) and antero-posterior radius (r), aortic diameter (AD) by M-mode echo with 2D echo control; 3) isthmus--diaphragm pulse wave delay (PWD) by measurement of time, between the foot of aortic velocity curves, respectively in the isthmus and near the diaphragm; 4) sternal length (L). We derived WT/r ratio, pulse wave velocity (PWV) as the ratio L/PWD, the product AD X PWD and the PWD/AD. AP, WT/r, PWD, PWV, AD, AD X CFD, PWD/AD are significantly correlated with age (respective r = 0.30, p = 0.05; r = 0.61, p less than 0.001; r = -0.67, p less than 0.001; r = 0.73, p less than 0.001; r = 0.61, p less than 0.001; r = -0.49, p less than 0.001; r = 0.52, p less than 0.001. WT/r is significantly correlated with PWD (r = -0.52, p less than 0.001); PWV (r = 0.50, p less than 0.001); AD (r = 0.44, p less than 0.03); AD X PWD (r = -0.38, p = 0.01) and PWD/AD (r = 0.35, p less than 0.02) but not systolic AP.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Aorta
  • Blood Pressure
  • Echocardiography, Doppler
  • Female
  • Heart Ventricles
  • Humans
  • Male
  • Middle Aged