The association between continuous ambulatory heart rate, heart rate variability, and 24-h rhythms of heart rate with familial longevity and aging.

Aging is associated with changes in heart rate (HR), heart rate variability (HRV), and 24-h rhythms in HR. Longevity has been linked to lower resting HR, while a higher resting HR and a decreased HRV were linked to cardiovascular events and increased mortality risk. HR and HRV are often investigated during a short electrocardiogram (ECG) measurement at a hospital.

Interrelationships Between Pituitary Hormones as Assessed From 24-hour Serum Concentrations in Healthy Older Subjects.

Context: Hormones of the hypothalamic-pituitary-target gland axes are mostly investigated separately, whereas the interplay between hormones might be as important as each separate hormonal axis.

Objective: Our aim is to determine the interrelationships between GH, TSH, ACTH, and cortisol in healthy older individuals.

Design: We made use of 24-hour hormone serum concentrations assessed with intervals of 10 minutes from 38 healthy older individuals with a mean age (SD) of 65.

Stress evokes stronger medial posterior cingulate deactivations during emotional distraction in slower paced aging.

Introduction: Middle-aged offspring from long-lived families are thought to have a slower pace of aging, possibly related to HPA-axis function. Here, we investigated the neural and behavioral effects of social stress in offspring compared to their regular aging partners on emotional distraction during working memory (WM).

Methods: 104 middle-aged participants (53 males) consisting of offspring and their partners underwent the Trier Social Stress Test or a control procedure.

Familial Longevity Is Not Associated with Major Differences in the Hypothalamic-Pituitary-Gonadal Axis in Healthy Middle-Aged Men.

Context: A trade-off between fertility and longevity possibly exists. The association of the male hypothalamic-pituitary-gonadal (HPG) axis with familial longevity has not yet been investigated.

Objective: To study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls.

Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity.

Reduced growth hormone (GH) signaling has been consistently associated with increased health and lifespan in various mouse models. Here, we assessed GH secretion and its control in relation with human familial longevity. We frequently sampled blood over 24 h in 19 middle-aged offspring of long-living families from the Leiden Longevity Study together with 18 of their partners as controls.

Association between the rs7903146 Polymorphism in the TCF7L2 Gene and Parameters Derived with Continuous Glucose Monitoring in Individuals without Diabetes.

Background: The rs7903146-T allele in the transcription factor 7-like 2 (TCF7L2) gene has been associated with impaired pancreatic insulin secretion, enhanced liver glucose production, and an increased risk of type 2 diabetes. Nevertheless, the impact of rs7903146 on daily glucose trajectories remains unclear. Continuous glucose monitoring (CGM) can estimate glycemia and glycemic variability based on consecutive glucose measurements collected over several days.

Physiological responding to stress in middle-aged males enriched for longevity: a social stress study.

Individuals enriched for familial longevity display a lower prevalence of age-related diseases, such as cardiovascular- and metabolic diseases. Since these diseases are associated with stress and increased cortisol levels, one of the underlying mechanisms that may contribute to healthy longevity might be a more adaptive response to stress. To investigate this, male middle-aged offspring from long-lived families (n = 31) and male non-offspring (with no familial history of longevity) (n = 26) were randomly allocated to the Trier Social Stress Test or a control condition in an experimental design.

Accuracy of Continuous Glucose Monitoring Measurements in Normo-Glycemic Individuals.

Background: The validity of continuous glucose monitoring (CGM) is well established in diabetic patients. CGM is also increasingly used for research purposes in normo-glycemic individuals, but the CGM validity in such individuals is unknown. We studied the accuracy of CGM measurements in normo-glycemic individuals by comparing CGM-derived versus venous blood-derived glucose levels and measures of glycemia and glycemic variability.

Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis.

Subclinical hypothyroidism (SCH), defined as elevated thyroid stimulating hormone (TSH) and normal thyroid hormone levels, and cognitive impairment are both common in older people. While the relation between overt hypothyroidism and cognitive impairment is well established, data on the association between SCH and cognitive impairment are conflicting. This systematic review and meta-analysis was performed to assess available evidence on the association of SCH with cognition in community dwelling, relatively healthy older adults.

Familial Longevity Is Associated With Higher TSH Secretion and Strong TSH-fT3 Relationship.

Context: Longevity is associated with changes in circulating levels of thyroid hormone (TH) and/or TSH in animals and humans, but underlying mechanisms remain elusive.

Objective: We explored in 38 offspring of nonagenarian participants from the Leiden Longevity Study, who are enriched for longevity and in their partners, ultradian and circadian rhythmicity of TSH, temporal relationship, and feedback and forward interplay between TSH and TH.

Methods: We collected blood samples every 10 minutes for 24 hours for TSH and TH profiles.

Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions.

Objective: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity.

Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes.

Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI.

Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age.

Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families ("offspring") and controls; and age categories thereof.

Familial longevity is marked by lower diurnal salivary cortisol levels: the Leiden Longevity Study.

Background: Reported findings are inconsistent whether hypothalamic-pituitary-adrenal (HPA) signaling becomes hyperactive with increasing age, resulting in increasing levels of cortisol. Our previous research strongly suggests that offspring from long-lived families are biologically younger. In this study we assessed whether these offspring have a lower HPA axis activity, as measured by lower levels of cortisol and higher cortisol feedback sensitivity.