Thyroid status and mortality in nonagenarians from long-lived families and the general population

Pathophysiology, epidemiology and therapy of agein

Gut microbiome changes due to sleep disruption in older and younger individuals: a case for sarcopenia?

Major hallmarks of functional loss, loss of metabolic and musculoskeletal health and (multi)morbidity with ageing are associated with sleep disturbances. With poor sleep shifts in gut microbial composition commonly manifest, which could mediate the proinflammatory state between sleep disturbances and sarcopenia. This systematic review presents the recent evidence on how sleep disturbances throughout the lifespan associate with and contribute to gut microbial composition changes, proposing a mechanism to understand the aetiology of sarcopenia through sleep disturbances. The relationship between disturbed sleep and clinically relevant gut microbiota composition on health aspects of ageing is discussed. A search was performed in PubMed, Cochrane Library, Scopus, Web of Science using keywords including (microbio* OR microflora) AND (sleep OR sleep disorder). Six cross-sectional population-based studies and five experimental clinical trials investigating healthy individuals with ages ranging from 4 to 71 were included. The cross-sectional studies reported similarities in associations with sleep disturbance and gut microbial diversity. In older adults, shorter sleep duration is associated with an increase in proinflammatory bacteria whereas increasing sleep quality is positively associated with an increase of beneficial Verrucomicrobia and Lentisphaerae phyla. In young adults, the effect of sleep disruption on gut microbiome composition, specifically the ratio of beneficial Firmicutes over Bacteroidetes phyla, remains contradictory and unclear. The findings of this review warrant further research in the modulation of the gut microbiome linking poor sleep with muscle-catabolic consequences throughout the lifespan

Copy number variation associates with mortality in long-lived individuals:a genome-wide assessment

Pathophysiology, epidemiology and therapy of agein

Plasma trimethylamine N-oxide (TMAO):associations with cognition, neuroimaging, and dementia

Background: The gut-derived metabolite Trimethylamine N-oxide (TMAO) and its precursors - betaine, carnitine, choline, and deoxycarnitine – have been associated with an increased risk of cardiovascular disease, but their relation to cognition, neuroimaging markers, and dementia remains uncertain. Methods: In the population-based Rotterdam Study, we used multivariable regression models to study the associations between plasma TMAO, its precursors, and cognition in 3,143 participants. Subsequently, we examined their link to structural brain MRI markers in 2,047 participants, with a partial validation in the Leiden Longevity Study (n = 318). Among 2,517 participants, we assessed the risk of incident dementia using multivariable Cox proportional hazard models. Following this, we stratified the longitudinal associations by medication use and sex, after which we conducted a sensitivity analysis for individuals with impaired renal function. Results: Overall, plasma TMAO was not associated with cognition, neuroimaging markers or incident dementia. Instead, higher plasma choline was significantly associated with poor cognition (adjusted mean difference: -0.170 [95% confidence interval (CI) -0.297;-0.043]), brain atrophy and more markers of cerebral small vessel disease, such as white matter hyperintensity volume (0.237 [95% CI: 0.076;0.397]). By contrast, higher carnitine concurred with lower white matter hyperintensity volume (-0.177 [95% CI: -0.343;-0.010]). Only among individuals with impaired renal function, TMAO appeared to increase risk of dementia (hazard ratio (HR): 1.73 [95% CI: 1.16;2.60]). No notable differences were observed in stratified analyses. Conclusions: Plasma choline, as opposed to TMAO, was found to be associated with cognitive decline, brain atrophy, and markers of cerebral small vessel disease. These findings illustrate the complexity of relationships between TMAO and its precursors, and emphasize the need for concurrent study to elucidate gut-brain mechanisms.</p

Plasma trimethylamine N-oxide (TMAO):associations with cognition, neuroimaging, and dementia

Background: The gut-derived metabolite Trimethylamine N-oxide (TMAO) and its precursors - betaine, carnitine, choline, and deoxycarnitine – have been associated with an increased risk of cardiovascular disease, but their relation to cognition, neuroimaging markers, and dementia remains uncertain. Methods: In the population-based Rotterdam Study, we used multivariable regression models to study the associations between plasma TMAO, its precursors, and cognition in 3,143 participants. Subsequently, we examined their link to structural brain MRI markers in 2,047 participants, with a partial validation in the Leiden Longevity Study (n = 318). Among 2,517 participants, we assessed the risk of incident dementia using multivariable Cox proportional hazard models. Following this, we stratified the longitudinal associations by medication use and sex, after which we conducted a sensitivity analysis for individuals with impaired renal function. Results: Overall, plasma TMAO was not associated with cognition, neuroimaging markers or incident dementia. Instead, higher plasma choline was significantly associated with poor cognition (adjusted mean difference: -0.170 [95% confidence interval (CI) -0.297;-0.043]), brain atrophy and more markers of cerebral small vessel disease, such as white matter hyperintensity volume (0.237 [95% CI: 0.076;0.397]). By contrast, higher carnitine concurred with lower white matter hyperintensity volume (-0.177 [95% CI: -0.343;-0.010]). Only among individuals with impaired renal function, TMAO appeared to increase risk of dementia (hazard ratio (HR): 1.73 [95% CI: 1.16;2.60]). No notable differences were observed in stratified analyses. Conclusions: Plasma choline, as opposed to TMAO, was found to be associated with cognitive decline, brain atrophy, and markers of cerebral small vessel disease. These findings illustrate the complexity of relationships between TMAO and its precursors, and emphasize the need for concurrent study to elucidate gut-brain mechanisms.</p

Decreased Levels of Bisecting GlcNAc Glycoforms of IgG Are Associated with Human Longevity

BACKGROUND: Markers for longevity that reflect the health condition and predict healthy aging are extremely scarce. Such markers are, however, valuable in aging research. It has been shown previously that the N-glycosylation pattern of human immunoglobulin G (IgG) is age-dependent. Here we investigate whether N-linked glycans reflect early features of human longevity. METHODOLOGY/PRINCIPAL FINDINGS: The Leiden Longevity Study (LLS) consists of nonagenarian sibling pairs, their offspring, and partners of the offspring serving as control. IgG subclass specific glycosylation patterns were obtained from 1967 participants in the LLS by MALDI-TOF-MS analysis of tryptic IgG Fc glycopeptides. Several regression strategies were applied to evaluate the association of IgG glycosylation with age, sex, and longevity. The degree of galactosylation of IgG decreased with increasing age. For the galactosylated glycoforms the incidence of bisecting GlcNAc increased as a function of age. Sex-related differences were observed at ages below 60 years. Compared to males, younger females had higher galactosylation, which decreased stronger with increasing age, resulting in similar galactosylation for both sexes from 60 onwards. In younger participants (<60 years of age), but not in the older age group (>60 years), decreased levels of non-galactosylated glycoforms containing a bisecting GlcNAc reflected early features of longevity. CONCLUSIONS/SIGNIFICANCE: We here describe IgG glycoforms associated with calendar age at all ages and the propensity for longevity before middle age. As modulation of IgG effector functions has been described for various IgG glycosylation features, a modulatory effect may be expected for the longevity marker described in this study

Late reproduction is associated with extended female survival but not with familial longevity

Research question: Are age at last childbirth and number of children, as facets of female reproductive health, related to individual lifespan or familial longevity? Design: This observational study included 10,255 female participants from a multigenerational historical cohort, the LINKing System for historical family reconstruction (LINKS), and 1258 female participants from 651 long-lived families in the Leiden Longevity Study (LLS). Age at last childbirth and number of children, as outcomes of reproductive success, were compared with individual and familial longevity using the LINKS dataset. In addition, the genetic predisposition in the form of a polygenic risk score (PRS) for age at menopause was studied in relation to familial longevity using the LLS dataset. Results: For each year increase in the age of the birth of the last child, a woman's lifespan increased by 0.06 years (22 days; P = 0.002). The yearly risk for having a last child was 9% lower in women who survived to the oldest 10% of their birth cohort (hazard ratio 0.91, 95% CI 0.86–0.95). Women who came from long-living families did not have a higher mean age of last childbirth. There was no significant association between familial longevity and genetic predisposition to age at menopause. Conclusions: Female reproductive health associates with a longer lifespan. Familial longevity does not associate to extended reproductive health. Other factors in somatic maintenance that support a longer lifespan are likely to have an impact on reproductive health

Link between foot pain severity and prevalence of depressive symptoms

OBJECTIVE: Associations between pain and depression are well known, yet foot pain, common in populations, has been understudied. This cross-sectional study examined foot pain and severity of foot pain with depressive symptoms in adults. METHODS: Framingham Foot Study (2002-2008) participants completed questionnaires that included questions about foot pain (yes/no; none, mild, moderate, or severe pain) and the Center for Epidemiologic Studies Depression Scale (scores ≥16 indicated depressive symptoms). Age and body mass index (BMI) were also assessed. Sex-specific logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations of foot pain with depressive symptoms, adjusting for age and BMI. In a subset, further models adjusted for leg pain, back pain, or other joint pain. RESULTS: Of 1,464 men and 1,857 women, the mean ± SD age was 66 ± 10 years. Depressive symptoms were reported in 21% of men and 27% of women. Compared to those with no foot pain and independent of age and BMI, both men and women with moderate foot pain had approximately a 2-fold increased odds of depressive symptoms (men with severe foot pain OR of 4 [95% CI 2.26-8.48], women with severe foot pain OR of 3 [95% CI 2.02-4.68]). Considering other pain regions attenuated ORs, but the pattern of results remained unchanged. CONCLUSION: Even after we adjusted for age, BMI, and other regions of pain, those reporting worse foot pain were more likely to report depressive symptoms. These findings suggest that foot pain may be a part of a broader pain spectrum, with an impact beyond localized pain and discomfort