GeroScience

The endogenous incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) possess neurotrophic, neuroprotective, and anti-neuroinflammatory actions. The dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin reduces degradation of endogenous GLP-1 and GIP, and, thereby, extends the circulation of these protective peptides. The current nonhuman primate (NHP) study evaluates whether human translational sitagliptin doses can elevate systemic and central nervous system (CNS) levels of GLP-1/GIP in naive, non-lesioned NHPs, in line with our prior rodent studies that demonstrated sitagliptin efficacy in preclinical models of Parkinson's disease (PD)...

An increase in systemic inflammation (inflammaging) is one of the hallmarks of aging. Epigenetic (DNA methylation) clocks can quantify the degree of biological aging and this can be reversed by lifestyle and pharmacological intervention. We aimed to investigate whether a multi-component nutritional supplement could reduce systemic inflammation and epigenetic age in healthy older adults.We recruited 80 healthy older participants (mean age ± SD: 71.85 ± 6.23; males = 31, females = 49)...

Age-related deterioration of condylar cartilage is an etiological factor in temporomandibular joint-osteoarthritis (TMJ-OA). However, its underlying mechanism remains unknown. Therefore, we examined age-related changes and the relationship between mTOR signaling and primary cilia in condylar cartilage to determine the intrinsic mechanisms of age-related TMJ-OA. Age-related morphological changes were analyzed using micro-computed tomography and safranin O-stained histological samples of the mandibular condyle of C57BL/6J mice (up to 78 weeks old)...

To examine cross-sectional and longitudinal relationships of psychotropic medications with physical function after menopause. Analyses involved 4557 Women's Health Initiative Long Life Study (WHI-LLS) participants (mean age at WHI enrollment (1993-1998): 62.8 years). Antidepressant, anxiolytic, and sedative/hypnotic medications were evaluated at WHI enrollment and 3-year follow-up visits. Performance-based physical function [Short Physical Performance Battery (SPPB)] was assessed at the 2012-2013 WHI-LLS visit...

Emerging research underscores the pivotal role of adipose tissue in regulating systemic aging processes, particularly when viewed through the lens of the endocrine hypotheses of aging. This study delves into the unique adipose characteristics in an important animal model of aging - the long-lived Ames dwarf (df/df) mice. Characterized by a Prop1df gene mutation, these mice exhibit a deficiency in growth hormone (GH), prolactin, and TSH, alongside extremely low circulating IGF-1 levels. Intriguingly, while surgical removal of visceral fat (VFR) enhances insulin sensitivity in normal mice, it paradoxically increases insulin resistance in Ames dwarfs...

Behavioral evidence showed decreased cognitive flexibility in older adults. However, task-based network mechanisms of cognitive flexibility in aging (CFA) remain unclear. Here, we provided the first task-state network evidence that CFA was associated with inadequate preparation for switching trials by revealing age-related changes in functional integration. We examined functional integration in a letter-number switch task that distinguished between the cue and target stages. Both young and older adults showed decreased functional integration from the cue stage to the target stage, indicating that control-related processes were executed as the task progressed...

Aging-induced aortic stiffness has been associated with altered fatty acid metabolism. We studied aortic stiffness using cardiac magnetic resonance (CMR)-assessed ventriculo-arterial coupling (VAC) and novel aortic (AO) global longitudinal strain (GLS) combined with targeted metabolomic profiling. Among community older adults without cardiovascular disease, VAC was calculated as aortic pulse wave velocity (PWV), a marker of arterial stiffness, divided by left ventricular (LV) GLS. AOGLS was the maximum absolute strain measured by tracking the phasic distance between brachiocephalic artery origin and aortic annulus...

Healthy longevity medicine integrates geroscience and other disciplines into clinical settings, aiming to optimize health throughout one's lifespan. Multiple factors have led to increased consumer engagement, with private clinics currently meeting the demand for guidance to improve healthy longevity. The establishment of healthy longevity clinics in publicly funded hospitals is a significant development, making longevity-focused healthcare more accessible. These clinics rely on multidisciplinary teams of physicians and allied health professionals...

Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups...

The current study investigates whether there are statistically independent age-related influences on the canine cognitive structure and how individual factors moderate cognitive aging on both cross-sectional and longitudinal samples. A battery of seven tasks was administered to 129 pet dogs, on which exploratory and confirmatory factor analyses were employed to unveil the correlational structure underlying individual differences in cognitive performance. The best-fitting model featured a hierarchical structure with two first-order cognitive domains (individual problem solving, learning) and a second-order common factor...

Despite the universal impact of sarcopenia on compromised health and quality of life in the elderly, promising pharmaceutical approaches that can effectively mitigate loss of muscle and function during aging have been limited. Our group and others have reported impairments in peripheral motor neurons and loss of muscle innervation as initiating factors in sarcopenia, contributing to mitochondrial dysfunction and elevated oxidative stress in muscle. We recently reported a reduction in α motor neuron loss in aging mice in response to the compound OKN-007, a proposed antioxidant and anti-inflammatory agent...

The postmenopausal decrease in circulating estradiol (E2) levels has been shown to contribute to several adverse physiological and psychiatric effects. To elucidate the molecular effects of E2 on the brain, we examined differential gene expression and DNA methylation (DNAm) patterns in the nonhuman primate brain following ovariectomy (Ov) and subsequent subcutaneous bioidentical E2 chronic treatment. We identified several dysregulated molecular networks, including MAPK signaling and dopaminergic synapse response, that are associated with ovariectomy and shared across two different brain areas, the occipital cortex (OC) and prefrontal cortex (PFC)...

The incidence of aortic valve stenosis (AoS) increases with age, and once diagnosed, symptomatic severe AoS has a yearly mortality rate of 25%. AoS is diagnosed with transthoracic echocardiography (TTE), however, this gold standard is time consuming and operator and acoustic window dependent. As AoS affects the arterial blood pressure waveform, AoS-specific waveform features might serve as a diagnostic tool. Aim of the present study was to develop a novel, non-invasive, AoS detection model based on blood pressures waveforms...

Chronic periodontitis and its keystone pathogen, Porphyromonas gingivalis, have increasingly been linked with Alzheimer's disease (AD). However, P.gingivalis-lipopolysaccharide (LPS) mediated release of neuroinflammatory proteins contributes to AD remains underexplored. In this study, we utilized data-independent acquisition mass spectrometry to characterize P.gingivalis-LPS induced profile of differentially expressed proteins associated with the neuroinflammatory response in human neuroblastoma (SH-SY5Y) and human microglial (HMC3) cells...

Mice with cardiac-specific overexpression of adenylyl cyclase (AC) type 8 (TGAC8 ) are under a constant state of severe myocardial stress. They have a remarkable ability to adapt to this stress, but they eventually develop accelerated cardiac aging and experience reduced longevity. We have previously demonstrated through bioinformatics that constitutive adenylyl cyclase activation in TGAC8 mice is associated with the activation of inflammation-related signaling pathways. However, the immune response associated with chronic myocardial stress in the TGAC8 mouse remains unexplored...

Di-(2-ethylhexyl) phthalate (DEHP), a prevalent plasticizer, is known to have endocrine-disrupting effects on males and cause reproductive toxicity. There were causal effects of DEHP on testosterone levels in the real world by Mendelian randomization analysis. Exposure to DEHP during the preadult stage might lead to premature testicular senescence, but the mechanisms responsible for this have yet to be determined. In this study, we administered DEHP (300 mg/kg/day) to male C57BL/6 mice from postnatal days 21 to 49...

The decline in the ovarian reserve leads to menopause and reduced serum estrogens. MicroRNAs are small non-coding RNAs, which can regulate gene expression and be secreted by cells and trafficked in serum via exosomes. Serum miRNAs regulate tissue function and disease development. Therefore, the aim of this study was to identify miRNA profiles in serum exosomes of mice induced to estropause and treated with 17β-estradiol (E2). Female mice were divided into three groups including control (CTL), injected with 4-Vinylcyclohexene diepoxide (VCD), and injected with VCD plus E2 (VCD + E2 )...

Aging is the basis of neurodegeneration and dementia that affects each endemic in the body. Normal aging in the brain is associated with progressive slowdown and disruptions in various abilities such as motor ability, cognitive impairment, decreasing information processing speed, attention, and memory. With the aggravation of global aging, more research focuses on brain changes in the elderly adult. The graph theory, in combination with functional magnetic resonance imaging (fMRI), makes it possible to evaluate the brain network functional connectivity patterns in different conditions with brain modeling...

Physical fitness has been extensively shown to strongly associate with general health status and major health risks. Here we tested the ability of a novel estimate of fitness age (FitAge) to differentiate aging trajectories.This study aimed at (1) testing the ability of FitAge to differentiate aging patterns among decelerated, normal, and accelerated agers in selected health domains, (2) estimating the risk for developing major health issues depending on the aging trajectory, and (3) comparing FitAge to body mass index (BMI) categorization in differentiating healthy from unhealthy aging patterns...

Physical activity is a promising preventative strategy for Alzheimer's disease: it is associated with lower dementia risk, better cognition, greater brain volume and lower brain beta-amyloid. Blood-based biomarkers have emerged as a low-cost, non-invasive strategy for detecting preclinical Alzheimer's disease, however, there is limited literature examining the effect of exercise (a structured form of physical activity) on blood-based biomarkers. The current study investigated the influence of a 6-month exercise intervention on levels of plasma beta-amyloid (Aβ42, Aβ40, Aβ42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) chain in cognitively unimpaired older adults, and as a secondary aim, whether blood-based biomarkers related to cognition...