Biomarkers Of Aging Research Articles

Hormone therapy is associated with lower Alzheimer’s disease tau biomarkers in post-menopausal females -evidence from two independent cohorts

BackgroundFemales represent approximately 70% of the Alzheimer’s disease (AD) cases and the literature has proposed a connection between the decreased estrogen levels during menopause and an increased AD risk. Previous investigations have predominantly focused on assessing how hormone therapy (HT) affects the likelihood of AD development and cognitive deterioration. However, as the research framework has shifted toward a biomarker-defined AD and alterations in specific biomarkers could take place years before cognitive decline becomes discernible, it is crucial to examine how HT influences AD biomarkers. The main goal of this study was to evaluate the impact of HT on AD biomarker-informed pathophysiology in both cognitively unimpaired (CU) and cognitively impaired (CI) post-menopausal females across the aging and AD spectrum.MethodsThis cross-sectional study included post-menopausal females without HT history (HT-) and with HT (HT+) at the time of PET imaging assessment from two cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants underwent magnetic resonance imaging (MRI), positron emission tomography (PET) and biofluid collection. Voxel-based t-tests were performed to assess the differences in amyloid-β (Aβ) and tau neurofibrillary tangles (NFTs) loads between HT- and HT + females. Linear regression models with interaction terms were also conducted to examine the interactive effects of HT and Aβ-PET on regional tau-PET.ResultsHT + females demonstrated significantly lower tau-PET standardized uptake value ratio (SUVR) in Braak I-II ROIs (P < 0.05, Hedges’ g = 0.73), Braak III-IV ROIs (P < 0.0001, Hedges’ g = 0.74) and Braak V-VI ROIs (P < 0.0001, Hedges’ g = 0.69) compared to HT- females. HT + females also showed significantly lower CSF p-tau181 (P < 0.001) and plasma p-tau181 (P < 0.0001) concentrations. Additionally, results from multivariate linear regression models indicated that HT interacts with cortical Aβ and is associated with lower regional NFT load.ConclusionsOverall, findings from this observational study suggest that HT is associated with lower tau neuroimaging and fluid biomarkers in postmenopausal females. Due to the close link between tau and cognition, this study highlights the need for large randomized controlled trials designed to systemically study the influences of HT on AD biomarkers and disease progression.

Estimated Pulse Wave Velocity Is Associated With a Higher Risk of Dementia in the Health and Retirement Study.

In this paper, we use the Health and Retirement Study (HRS) to examine the relationship between an estimated measure of pulse wave velocity (ePWV) and cognitive impairment with no dementia and dementia, respectively. We modeled the relationship between ePWV and cognitive status in 2006/2008 using data from 8,492 men and women (mean age 68.6 years) controlling for age, blood pressure, sociodemographic, and socioeconomic characteristics (sex, race and ethnicity, education, income, wealth), health behaviors (smoking and physical activity), body mass index (BMI), health status and related medication use (history of cardiovascular disease, diabetes, and stroke), and cerebrovascular disease (CVD)-related biomarkers (C-reactive protein, cystatin-C, hemoglobin A1c, total cholesterol, high-density lipoprotein [HDL] cholesterol). We assess cognitive function with the 27-item Langa-Weir Telephone Interview for Cognitive Status (TICS) scale. ePWV is derived from an equation based on participant age and resting blood pressure. In a model that controlled for the constituent components of ePWV (age, age squared, systolic and diastolic blood pressure), ePWV is associated with increased odds of having cognitive impairment with no dementia (OR = 2.761) and dementia (OR = 6.344) relative to a group with no cognitive impairment or dementia. After controlling for the constituent components of ePWV, sociodemographic and socioeconomic characteristics, health behaviors, BMI, health status and medication use, and CVD-related biomarkers, ePWV remains significantly associated with dementia (OR = 3.969) but not cognitive impairment with no dementia (OR = 1.782). These findings suggest that ePWV may be a novel research tool and biomarker of vascular aging that can be used in large, population-representative studies to examine cognitive aging and dementia risk.

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1–7. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK–AMPK–mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people.

PRC2-AgeIndex as a universal biomarker of aging and rejuvenation

DNA methylation (DNAm) is one of the most reliable biomarkers of aging across mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, DNAm gain is less characterized. Studies have demonstrated that CpGs which gain methylation with age are enriched in Polycomb Repressive Complex 2 (PRC2) targets. However, whole-genome examination of all PRC2 targets as well as determination of the pan-tissue or tissue-specific nature of these associations is lacking. Here, we show that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells (PRC2 LMRs) gain methylation with age in all examined somatic mitotic cells. We estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the “PRC2-AgeIndex,” defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells which can distinguish the effect of different anti-aging interventions.

Does Adulthood Socioeconomic Status Predict Subsequent Telomere Length in Racially and Ethnically Diverse Women?

Telomere length is a critical biomarker of cellular aging and overall health. While childhood socioeconomic status (SES) indicators such as education and poverty can have long-lasting effects on biological aging, research has shown contradictory results regarding the impact of adulthood SES on future telomere length, particularly in racially and ethnically diverse individuals. This study investigates the effects of baseline adulthood SES indicators such as education and poverty on telomere length nine years later in women, using data from the Future of Families and Child Wellbeing Study (FFCWS). We analyzed data from the FFCWS, a longitudinal cohort study. The sample included baseline adulthood SES and follow-up telomere length measure of women (n = 2,421) with varying socioeconomic conditions. Telomere length was measured from saliva samples nine years after the baseline measure of adulthood SES. Education, poverty, and marital status at baseline were assessed. Multivariate linear regression models were used to examine the association between adulthood SES indicators at baseline and future telomere length, controlling for potential confounders. From the total 2,421 women, 675 were Latino White, 1,158 were non-Latino Black, and 588 were non-Latino White. Our findings indicate that for non-Latino White women poverty at certain level, and childbirth weight, and for non-Latino Black maternal age were predictors of telomere lengths nine years later. Poverty at a specific level, maternal age and childbirth weight serve as predictors of telomere lengths nine years later in some women. These findings underscore the importance of socioeconomic factors and early-life influences in understanding telomere dynamics and aging processes among women from varied racial and ethnic backgrounds.

New insights into healthy ageing, inflammageing and frailty using metabolomics.

Human ageing is a normal process and does not necessarily result in the development of frailty. A mix of genetic, environmental, dietary, and lifestyle factors can have an impact on ageing, and whether an individual develops frailty. Frailty is defined as the loss of physiological reserve both at the physical and cellular levels, where systemic processes such as oxidative stress and inflammation contribute to physical decline. The newest "omics" technology and systems biology discipline, metabolomics, enables thorough characterisation of small-molecule metabolites in biological systems at a particular time and condition. In a biological system, metabolites-cellular intermediate products of metabolic reactions-reflect the system's final response to genomic, transcriptomic, proteomic, epigenetic, or environmental alterations. As a relatively newer technique to characterise metabolites and biomarkers in ageing and illness, metabolomics has gained popularity and has a wide range of applications. We will give a comprehensive summary of what is currently known about metabolomics in studies of ageing, with a focus on biomarkers for frailty. Metabolites related to amino acids, lipids, carbohydrates, and redox metabolism may function as biomarkers of ageing and/or frailty development, based on data obtained from human studies. However, there is a complexity that underpins biological ageing, due to both genetic and environmental factors that play a role in orchestrating the ageing process. Therefore, there is a critical need to identify pathways that contribute to functional decline in people with frailty.

Functional and structural neuroretinal disorders in HIV Controllers. Prospective cohort study.

To estimate the prevalence and cumulative incidence of neuro-retinal-disorders (NRD) in HIV-controllers. Prospective, single-centre, cohort study of people living with HIV (PLWH): elite-controllers, long-term-non-progressors and early diagnosed. The study compared "HIV-controllers" (including elite-controllers and long-term-non-progressors), who were not on antiretroviral therapy (ART), and "HIV-treatment" (HIV-infected subjects with a recent diagnosis and on ART). A matched cohort of "non-HIV subjects" was created. NRD was defined as at least one altered (not normal) ophthalmological parameter (functional or structural). Functional (visual acuity, contrast sensitivity, chromatic vision, visual field) and structural parameters (ganglion cells, macular nerve fibre layer, peripapillary nerve fibre layers, vascular calibre) as well as quality of life (Medical Outcomes Study-HIV Short Form-30) were assessed. Between March 2012 and November 2015, the study included all HIV-controllers (16 elite-controllers, 1 long-term-non-progressor), 11 HIV-treatment and 16 non-HIV. Prevalence of NRD at baseline was 88.2% (15/17, 95% CI: 65.7%-96.7%), 90.9% (10/11, 95% CI: 62.3%-98.4%) and 56.3% (9/16, 95% CI: 33.2%-76.9%), respectively. Cumulative incidence at 3 years was 50% (1/2), 100% (1/1) and 33.3% (2/6), respectively. None of the participants manifested ocular clinical symptoms. Three years later, prevalence of NRD was 92.3% (12/13, 95% CI: 66.7%-98.6%), 75% (6/8, 95% CI: 40.9%-92.9%) and 50.0% (7/14, 95% CI: 26.8%-73.2%), respectively. Contrast sensitivity and structural parameters were globally the most affected among PLWH. Quality of life (total score) [median (interquartile range)] at baseline and 3 years was 82 (71-89) and 74 (63.5-79.25) in HIV-controllers and 80 (73-88) and 88 (83-92) in HIV-treatment. HIV-controllers and those individuals on ART presented a higher percentage of NRD than non-HIV. Our results suggest that NRD could be a biomarker of ocular aging among PLWH.

Harnessing myelin water fraction as an imaging biomarker of human cerebral aging, neurodegenerative diseases, and risk factors influencing myelination: A review.

Myelin water fraction (MWF) imaging has emerged as a promising magnetic resonance imaging (MRI) biomarker for investigating brain function and composition. This comprehensive review synthesizes the current state of knowledge on MWF as a biomarker of human cerebral aging, neurodegenerative diseases, and risk factors influencing myelination. The databases used include Web of Science, Scopus, Science Direct, and PubMed. We begin with a brief discussion of the theoretical foundations of MWF imaging, including its basis in MR physics and the mathematical modeling underlying its calculation, with an overview of the most adopted MRI methods of MWF imaging. Next, we delve into the clinical and research applications that have been explored to date, highlighting its advantages and limitations. Finally, we explore the potential of MWF to serve as a predictive biomarker for neurological disorders and identify future research directions for optimizing MWF imaging protocols and interpreting MWF in various contexts. By harnessing the power of MWF imaging, we may gain new insights into brain health and disease across the human lifespan, ultimately informing novel diagnostic and therapeutic strategies.

The Impact of HIV and Parasite Single Infection and Coinfection on Telomere Length: A Systematic Review.

HIV and parasite infections accelerate biological aging, resulting in immune senescence, apoptosis and cellular damage. Telomere length is considered to be one of the most effective biomarkers of biological aging. HIV and parasite infection have been reported to shorten telomere length in the host. This systematic review aimed to highlight work that explored the influence of HIV and parasite single infections and coinfection on telomere length. Using specific keywords related to the topic of interest, an electronic search of several online databases (Google Scholar, Web of Science, Scopus, Science Direct and PubMed) was conducted to extract eligible articles. The association between HIV infection or parasite infection and telomere length and the association between HIV and parasite coinfection and telomere length were assessed independently. The studies reported were mostly conducted in the European countries. Of the 42 eligible research articles reviewed, HIV and parasite single infections were independently associated with telomere length shortening. Some studies found no association between antiretroviral therapy (ART) and telomere length shortening, while others found an association between ART and telomere length shortening. No studies reported on the association between HIV and parasite coinfection and telomere length. HIV and parasite infections independently accelerate telomere length shortening and biological aging. It is possible that coinfection with HIV and parasites may further accelerate telomere length shortening; however, this is a neglected field of research with no reported studies to date.

QMAP enabled microanatomical mapping of human skin aging.

Aging is a major driver of diseases in humans. Identifying features associated with aging is essential for designing robust intervention strategies and discovering novel biomarkers of aging. Extensive studies at both the molecular and organ/whole-body physiological scales have helped determined features associated with aging. However, the lack of meso-scale studies, particularly at the tissue level, limits the ability to translate findings made at molecular scale to impaired tissue functions associated with aging. In this work, we established a tissue image analysis workflow - quantitative micro-anatomical phenotyping (qMAP) - that leverages deep learning and machine vision to fully label tissue and cellular compartments in tissue sections. The fully mapped tissue images address the challenges of finding an interpretable feature set to quantitatively profile age-related microanatomic changes. We optimized qMAP for skin tissues and applied it to a cohort of 99 donors aged 14 to 92. We extracted 914 microanatomic features and found that a broad spectrum of these features, represented by 10 cores processes, are strongly associated with aging. Our analysis shows that microanatomical features of the skin can predict aging with a mean absolute error (MAE) of 7.7 years, comparable to state-of-the-art epigenetic clocks. Our study demonstrates that tissue-level architectural changes are strongly associated with aging and represent a novel category of aging biomarkers that complement molecular markers. Our results highlight the complex and underexplored multi-scale relationship between molecular and tissue microanatomic scales.

O-078 Deletion of interlukin-17A protects against ovarian aging via activating wnt10b/β-catenin signaling

Abstract Study question Is there any compelling evidence to suggest that the deletion of IL17A could potentially ameliorate ovarian aging? Summary answer IL17A is elevated in the follicular fluid of aged women. Knocking out Il17a in mice improves ovarian aging phenotypes by activating Wnt10b/β-catenin signaling. What is known already Inflammation, a hallmark of aging, negatively impacts female fertility. Interleukin 17 (IL-17) cytokines, including IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F, are signature cytokines of T helper 17 cells. IL-17A, the first-discovered and well-explored among them, has been predominantly characterized as a kind of proinflammatory cytokine and a promoter in the pathogenesis of chronic autoimmune diseases such as psoriasis and ankylosing spondylitis. Significant accumulation of CD4-CD8-double-negative T cells in aged mouse ovaries, identified as a crucial source of IL-17, was reported via single-cell RNA sequencing. However, much remains unknown about the IL17 and ovarian aging relationship. Study design, size, duration Follicular fluid was collected from 51 women (age≥35 years) and 37 controls (age &amp;lt;35 years) at the Southern Medical University Southern Hospital's Reproductive Center to measure IL17A levels from March 2022 to August 2023. Additionally, we generated Il-17a knockout (Il17-a KO) mice (42 KO mice and 49 controls) to elucidate the role of Il-17a in ovarian aging in vivo. Further, RNA-seq was employed to explore the mechanism involved in the Il17a-associated ovarian aging. Participants/materials, setting, methods Clinical data were compared from two infertile patient cohorts. IL17A levels in follicular fluid were quantified using ELISA. Pearson correlation analysis explored the relationship between IL17A levels and age, ovarian reserve, and clinical outcomes. We also assessed aging-related phenotypes in Il17a-KO and WT mice at 3, 8, 12, and 15 months of age. Fertility assessment, ovarian reserve, histological analysis, mason staining, western blot analysis, qRT-PCR, IVF, spindle formation, and RNA-seq were used in this study. Main results and the role of chance Elevated IL17A levels in follicular fluid from aged patients were observed and may be used as a sensitive biomarker for advanced age (P &amp;lt; 0.001). Deletion of Il17a not only enhanced fertility and ovarian reserve in mice but also ameliorated inflammation, the senescent associated secretory phenotype (SASP), senescence and fibrosis. RNA-seq analysis identified 705 differentially expressed genes, primarily enriched in the Wnt10b signaling pathway. Validation experiments suggested that IL-17A deficiency may improve ovarian aging by upregulating wnt10b expression, promoting β-catenin nuclear translocation, and activating downstream molecules (c-Myc, Cyclin D1, c-jun). Limitations, reasons for caution This study found a correlation between IL17A and aging. However, how knocking out IL17A promotes the increase of Wnt10b and other potential functions of Il17a in ovarian aging remain to be further explored. Wider implications of the findings This study shows new insights into the mechanisms of IL17A in ovarian aging and provides potential biomarkers and therapeutic targets for the treatment of ovarian aging. In the future, a larger sample of studies are needed to investigate the relationship between IL17A and aged women. Trial registration number not applicable

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo

BackgroundRestraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan.MethodsUsing Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture.ResultsWe developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo.ConclusionsOur method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

Telomere Length in a South African Population Co-Infected with HIV and Helminths.

Biological ageing refers to the gradual decrease in physiological functions, resulting in immune senescence, cellular damage and apoptosis. Telomere length is a biomarker of biological ageing. Limited studies have associated shorter telomere length with HIV and parasite single infections, with no studies reporting the association of HIV and parasite co-infection with telomere length. The study aimed to investigate whether telomere length shortening is accelerated in a South African population co-infected with HIV and helminths compared to participants singly infected with either HIV or helminths. Additionally, telomere length data were compared with participants' biochemical and full blood count parameters. A total of 200 participants were in groups of uninfected control, HIV single infection, helminth single infection and HIV and helminth co-infection groups. Relative telomere length (RTL) was determined using Real-Time PCR and associated with biochemical and full blood count parameters using multivariate regression analysis models that were adjusted for confounders. The uninfected control group was used as a reference group. The uninfected control group had the highest mean RTL (1.21 ± 0.53) while the HIV-infected (0.96 ± 0.42) and co-infected (0.93 ± 0.41) groups had similar RTLs, and lastly, the helminth-infected group (0.83 ± 0.33) had the lowest RTL (p = 0.0002). When compared to the uninfected control group, a significant association between RTL and biochemical parameters, including blood iron (β = -0.48), ferritin (β = -0.48), transferrin saturation (β = -0.57), transferrin (β = -0.57), phosphate (β = -0.47), vitamin A (β = -0.49) and C-reactive protein (β = -0.52) were noted in the co-infected group (p < 0.05). In addition, a significant association between RTL and full blood count, including (β = -0.47), haematocrit (β = -0.46), mean corpuscular volume (β = -0.47), lymphocytes (β = -0.45), mean corpuscular haemoglobin concentration (β = -0.45), red cell distribution width (β = -0.47), monocytes (β = -0.45), eosinophils (β = -0.45), basophils (β = -0.44) and transferrin saturation (β = -0.57) were also noted in the co-infected group (p < 0.05). Accelerated biological ageing, as indicated by telomere length shortening, is associated with HIV and helminth co-infections.

Association of retinal age gap with chronic kidney disease and subsequent cardiovascular disease sequelae: a cross-sectional and longitudinal study from the UK Biobank.

Chronic kidney disease (CKD) increases the risk of cardiovascular disease (CVD) and is more prevalent in older adults. Retinal age gap, a biomarker of aging based on fundus images, has been previously developed and validated. This study aimed to investigate the association of retinal age gap with CKD and subsequent CVD complications. A deep learning model was trained to predict the retinal age using 19200 fundus images of 11052 participants without any medical history at baseline. Retinal age gap, calculated as retinal age predicted minus chronological age, was calculated for the remaining 35906 participants. Logistic regression models and Cox proportional hazards regression models were used for the association analysis. A total of 35906 participants (56.75±8.04 years, 55.68% female) were included in this study. In the cross-sectional analysis, each 1-year increase in retinal age gap was associated with a 2% increase in the risk of CKD prevalence [odds ratio 1.02, 95% confidence interval (CI) 1.01-1.04, P=.012]. A longitudinal analysis of 35039 participants demonstrated that 2.87% of them developed CKD in follow-up, and each 1-year increase in retinal age gap was associated with a 3% increase in the risk of CKD incidence (hazard ratio 1.03, 95% CI 1.01-1.05, P=.004). In addition, a total of 111 CKD patients (15.81%) developed CVD in follow-up, and each 1-year increase in retinal age gap was associated with a 10% increase in the risk of incident CVD (hazard ratio 1.10, 95% CI 1.03-1.17, P=.005). We found that retinal age gap was independently associated with the prevalence and incidence of CKD, and also associated with CVD complications in CKD patients. This supports the use of this novel biomarker in identifying individuals at high risk of CKD and CKD patients with increased risk of CVD.

Plasma and CSF biomarkers of aging and cognitive decline in Caribbean vervets.

Vervets are non-human primates that share high genetic homology with humans and develop amyloid beta (Aβ) pathology with aging. We expand current knowledge by examining Aβ pathology, aging, cognition, and biomarker proteomics. Amyloid immunoreactivity in the frontal cortex and temporal cortex/hippocampal regions from archived vervet brain samples ranging from young adulthood to old age was quantified. We also obtained cognitive scores, plasma samples, and cerebrospinal fluid (CSF) samples in additional animals. Plasma and CSF proteins were quantified with platforms utilizing human antibodies. We found age-related increases in Aβ deposition in both brain regions. Bioinformatic analyses assessed associations between biomarkers and age, sex, cognition, and CSF Aβ levels, revealing changes in proteins related to immune-related inflammation, metabolism, and cellular processes. Vervets are an effective model of aging and early-stage Alzheimer's disease, and we provide translational biomarker data that both align with previous results in humans and provide a basis for future investigations. We found changes in immune and metabolic plasma biomarkers associated with age and cognition. Cerebrospinal fluid (CSF) biomarkers revealed changes in cell signaling indicative of adaptative processes. TNFRSF19 (TROY) and Artemin co-localize with Alzheimer's disease pathology. Vervets are a relevant model for translational studies of early-stage Alzheimer's disease.

Lifestyle factors and metabolomic aging biomarkers: Meta-analysis of cross-sectional and longitudinal associations in three prospective cohorts

Biological age uses biophysiological information to capture a person’s age-related risk of adverse outcomes. MetaboAge and MetaboHealth are metabolomics-based biomarkers of biological age trained on chronological age and mortality risk, respectively. Lifestyle factors contribute to the extent chronological and biological age differ. The association of lifestyle factors with MetaboAge and MetaboHealth, potential sex differences in these associations, and MetaboAge’s and MetaboHealth’s sensitivity to lifestyle changes have not been studied yet.Linear regression analyses and mixed-effect models were used to examine the cross-sectional and longitudinal associations of scaled lifestyle factors with scaled MetaboAge and MetaboHealth in 24,332 middle-aged participants from the Doetinchem Cohort Study, Rotterdam Study, and UK Biobank. Random-effect meta-analyses were performed across cohorts. Repeated metabolomics measurements had a ten-year interval in the Doetinchem Cohort Study and a five-year interval in the UK Biobank.In the first study incorporating longitudinal information on MetaboAge and MetaboHealth, we demonstrate associations between current smoking, sleeping ≥8 hours/day, higher BMI, and larger waist circumference were associated with higher MetaboHealth, the latter two also with higher MetaboAge. Furthermore, adhering to the dietary and physical activity guidelines were inversely associated with MetaboHealth. Lastly, we observed sex differences in the associations between alcohol use and MetaboHealth.

Associations between epigenetic aging and diabetes mellitus in a Swedish longitudinal study

Diabetes mellitus type 2 (T2D) is associated with accelerated biological aging and the increased risk of onset of other age-related diseases. Epigenetic changes in DNA methylation levels have been found to serve as reliable biomarkers for biological aging. This study explores the relationship between various epigenetic biomarkers of aging and diabetes risk using longitudinal data. Data from the Swedish Adoption/Twin Study of Aging (SATSA) was collected from 1984 to 2014 and included 536 individuals with at least one epigenetic measurement. The following epigenetic biomarkers of aging were employed: DNAm PAI-1, DNAmTL, DunedinPACE, PCHorvath1, PCHorvath2, PCHannum, PCPhenoAge, and PCGrimAge. Firstly, longitudinal analysis of biomarker trajectories was done. Secondly, linear correlations between the biomarkers and time to diabetes were studied within individuals developing diabetes. Thirdly, Cox proportional hazards (PH) models were used to assess the associations between these biomarkers and time of diabetes diagnosis, with adjustments for chronological age, sex, education, smoking, blood glucose, and BMI. The longitudinal trajectories of the biomarkers revealed differences between individuals with and without diabetes. Smoothened average curves for DunedinPACE and DNAm PAI-1 were higher for individuals with diabetes around the age 60–70, compared to controls. Likewise, DunedinPACE and DNAm PAI-1 were higher closer to diabetes onset. However, no significant associations were found between the epigenetic biomarkers of aging and risk of diabetes in Cox PH models. Our findings suggest the potential value of developing epigenetic biomarkers specifically tailored to T2D, should we wish to model and explore the potential for predicting the disease.

Biomarkers of Cellular Senescence and Aging: Current State-of-the-Art, Challenges and Future Perspectives.

Population aging has increased the global prevalence of aging-related diseases, including cancer, sarcopenia, neurological disease, arthritis, and heart disease. Understanding aging, a fundamental biological process, has led to breakthroughs in several fields. Cellular senescence, evinced by flattened cell bodies, vacuole formation, and cytoplasmic granules, ubiquitously plays crucial roles in tissue remodeling, embryogenesis, and wound repair as well as in cancer therapy and aging. The lack of universal biomarkers for detecting and quantifying senescent cells, in vitro and in vivo, constitutes a major limitation. The applications and limitations of major senescence biomarkers, including senescence-associated β-galactosidase staining, telomere shortening, cell-cycle arrest, DNA methylation, and senescence-associated secreted phenotypes are discussed. Furthermore, explore senotherapeutic approaches for aging-associated diseases and cancer. In addition to the conventional biomarkers, this review highlighted the in vitro, in vivo, and disease models used for aging studies. Further, technologies from the current decade including multi-omics and computational methods used in the fields of senescence and aging are also discussed in this review. Understanding aging-associated biological processes by using cellular senescence biomarkers can enable therapeutic innovation and interventions to improve the quality of life of older adults.

Functional locus coeruleus imaging to investigate an ageing noradrenergic system

The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution functional MRI (fMRI), a reversal reinforcement learning task, and dedicated post-processing approaches were used to visualise age differences in LC function (N = 50). Increased LC responses were observed during emotionally and task-related salient events, with subsequent accelerations and decelerations in reaction times, respectively, indicating context-specific adaptive engagement of the LC. Moreover, older adults exhibited increased LC activation compared to younger adults, indicating possible compensatory overactivation of a structurally declining LC in ageing. Our study shows that assessment of LC function is a promising biomarker of cognitive aging.

A proteomic signature of healthspan.

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan (healthspan proteomic score (HPS)) using data from the UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins). A lower HPS was associated with higher mortality risk and several age-related conditions, such as COPD, diabetes, heart failure, cancer, myocardial infarction, dementia, and stroke. HPS showed superior predictive accuracy for these outcomes compared to chronological age and biological age measures. Proteins associated with HPS were enriched in hallmark pathways such as immune response, inflammation, cellular signaling, and metabolic regulation. Our findings demonstrate the validity of HPS, making it a valuable tool for assessing healthspan and as a potential surrogate marker in geroscience-guided studies.