bims-caglex 2023-11-26 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2023–11–26
27 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Quantification of healthspan in aging mice: Introducing FAMY and GRAIL.
NMR metabolomic modelling of age and lifespan: a multi-cohort analysis.
Entorhinal Cortex Thinning is Related to White Matter Hyperintensity Growth, Memory Decline, and Leisure Activity in Cognitively Healthy Older Adults.
Epigenetic aging of mammalian gametes.
Heterogeneity of increased biological age in type 2 diabetes correlates with differential tissue DNA methylation, biological variables, and pharmacological treatments.
Food Insecurity, Memory, and Dementia Among US Adults Aged 50 Years and Older.
Associations of Objective and Self-Reported Physical Activity and Sedentary Behavior with Skeletal Muscle Energetics: The Study of Muscle, Mobility and Aging (SOMMA).
More play and fewer screens: a way to improve preschoolers' mental health? Cross-sectional findings from the British Preschool-children's Play Survey.
Lower Physical Activity Modifies the Association between Perceived Fatigability and Executive Function but not Memory: The Study of Muscle, Mobility and Aging (SOMMA).
Educational patterning in biological health seven years apart: Findings from the Tromsø Study.
Telomere shortening induces aging-associated phenotypes in hiPSC-derived neurons and astrocytes.
Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood.
Dose-response of accelerometer-measured physical activity, step count, and cancer risk in the UK Biobank: a prospective cohort analysis.
Influence of blood pressure polygenic risk scores and environmental factors on coronary artery disease in the Korean Genome and Epidemiology Study.
Deficit Accumulation Index and Biological Markers of Aging in Survivors of Childhood Cancer.
Moderating effect of country-level health determinants on the association between hobby engagement and mental health: cross-cohort multi-level models, meta-analyses, and meta-regressions.
Social connectedness, functional capacity, and longevity: A focus on positive relations with others.
Association Between Mid-arm Muscle Circumference and Cognitive Function: A Longitudinal Study of Chinese Adults.
Music Engagement as a Source of Cognitive Reserve.
The Skin and Inflamm-Aging.
Evaluation of lifestyle and dietary inflammatory score and their relationship with the odds of depression, stress, and anxiety in adults living in Yazd, Iran; based on YaHS and TAMYZ cohort study.
The 'faulty male' hypothesis for sex-biased mutation and disease.
Association of dietary inflammatory potential, dietary oxidative balance score and biological aging.
The Molecular Role of Polyamines in Age-Related Diseases: An Update.
Causal relationship between depression and aging: a bidirectional two-sample Mendelian randomization study.
Association of Diet Quality with Hand Grip Strength Weakness and Asymmetry in A Multi-ethnic Asian Cohort.
Social determinants of mental health trajectories during midlife: a prospective British birth cohort study.

bioRxiv. 2023 Nov 10. pii: 2023.11.07.566044. [Epub ahead of print]

Quantification of healthspan in aging mice: Introducing FAMY and GRAIL.

Dudley W Lamming.

The population around the world is graying, and as many of these individuals will spend years suffering from the burdens of age associated diseases, understanding how to increase healthspan, defined as the period of life free from disease and disability, is an urgent priority of geroscience research. The lack of agreed-upon quantitative metrics for measuring healthspan in aging mice has slowed progress in identifying interventions that do not simply increase lifespan, but also healthspan. Here, we define FAMY (Frailty-Adjusted Mouse Years) and GRAIL (Gauging Robust Aging when Increasing Lifespan) as new summary statistics for quantifying healthspan in mice. FAMY is based entirely on a widely utilized clinical frailty index, while GRAIL incorporates frailty, widely utilized healthspan assays, and information about the hallmarks of aging. Both metrics are conceptually similar to quality-adjusted life years (QALY), a widely-utilized measure of disease burden in humans, and can be readily calculated from data acquired during longitudinal and cross-sectional studies of mouse aging. We find that interventions generally thought to promote health, including calorie restriction, robustly improve healthspan as measured by FAMY and GRAIL. Finally, we show that use of GRAIL provides new insights, and identify dietary restriction of protein or isoleucine as an intervention that promotes healthspan but not longevity in female HET3 mice. We suggest that the routine integration of these measures into studies of aging in mice will allow the identification and development of interventions that promote healthy aging even in the absence of increased lifespan.

DOI: https://doi.org/10.1101/2023.11.07.566044
medRxiv. 2023 Nov 08. pii: 2023.11.07.23298200. [Epub ahead of print]

NMR metabolomic modelling of age and lifespan: a multi-cohort analysis.

Chung-Ho E Lau, Maria Manou, Georgios Markozannes, Mika Ala-Korpela, Yoav Ben- Shlomo, Nish Chaturvedi, Jorgen Engmann, Aleksandra Gentry-Maharaj, Karl-Heinz Herzig, Aroon Hingorani, Marjo-Riitta Järvelin, Mika Kähönen, Mika Kivimäki, Terho Lehtimäki, Saara Marttila, Usha Menon, Patricia B Munroe, Saranya Palaniswamy, Rui Providencia, Olli Raitakari, Floriaan Schmidt, Sylvain Sebert, Andrew Wong, Paolo Vineis, Ioanna Tzoulaki, Oliver Robinson.

Metabolomic age models have been proposed for the study of biological aging, however they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. 98 metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈ 31,000 individuals, age range 24-86 years). We used non-linear and penalised regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with ageing risk factors and phenotypes. Within the UK Biobank (N≈ 102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, chronic obstructive pulmonary disease) and all-cause mortality. Cross-validated Pearson's r between metabolomic age models and CA ranged between 0.47-0.65 in the training set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with chronological age were modest ( r = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06 / metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability.

DOI: https://doi.org/10.1101/2023.11.07.23298200
Neuroimage. 2023 Nov 17. pii: S1053-8119(23)00612-2. [Epub ahead of print] 120461

Entorhinal Cortex Thinning is Related to White Matter Hyperintensity Growth, Memory Decline, and Leisure Activity in Cognitively Healthy Older Adults.

Isabel Hotz, Pascal Frédéric Deschwanden, Susan Mérillat, Lutz Jäncke.

   INTRODUCTION: Cerebral small vessel disease (cSVD) is a growing epidemic that affects brain health and cognition. Therefore, a more profound understanding of the interplay between cSVD, brain atrophy, and cognition in healthy aging is of great importance. In this study, we examined the association between white matter hyperintensities (WMH) volume, number of lacunes, entorhinal cortex (EC) thickness, and declarative memory in cognitively healthy older participants over a seven-year period, controlling for possible confounding factors. Because there is no cure for cSVD to date, the neuroprotective potential of an active lifestyle has been suggested. Supporting evidence, however, is scarce. Therefore, a second objective of this study is to examine the relationship between leisure activities, cSVD, EC thickness, and declarative memory.
METHODS: We used a longitudinal dataset, which consisted of five measurement time points of structural MRI and psychometric cognitive ability and survey data, collected from a sample of healthy older adults (baseline N = 231, age range: 64 - 87 years, age M = 70.8 years), to investigate associations between cSVD MRI markers, EC thickness and verbal and figural memory performance. Further, we computed physical, social, and cognitive leisure activity scores from survey-based assessments and examined their associations with brain structure and declarative memory. To provide more accurate estimates of the trajectories and cross-domain correlations, we applied latent growth curve models controlling for potential confounders.
RESULTS: Less age-related thinning of the right (β = .92, p<.05) and left EC (β = .82, p<.05) was related to less declarative memory decline; and a thicker EC at baseline predicted less declarative memory loss (β = .54, p<.05). Higher baseline levels of physical (β = .24, p<.05), and social leisure activity (β = .27, p<.01) predicted less thinning of right EC. No relation was found between WMH or lacunes and declarative memory or between leisure activity and declarative memory. Higher education was initially related to more physical activity (β = .16, p<.05) and better declarative memory (β = .23, p<.001), which, however, declined steeper in participants with higher education (β = -.35, p<.05). Obese participants were less physically (β = -.18, p<.01) and socially active (β = -.13, p<.05) and had thinner left EC (β = -.14, p<.05) at baseline. Antihypertensive medication use (β = -.26, p<.05), and light-to-moderate alcohol consumption (β = -.40, p<.001) were associated with a smaller increase in the number of lacunes whereas a larger increase in the number of lacunes was observed in current smokers (β = .30, p<.05).
CONCLUSIONS: Our results suggest complex relationships between cSVD MRI markers (total WMH, number of lacunes, right and left EC thickness), declarative memory, and confounding factors such as antihypertensive medication, obesity, and leisure activitiy. Thus, leisure activities and having good cognitive reserve counteracting this neurodegeneration. Several confounding factors seem to contribute to the extent or progression/decline of cSVD, which needs further investigation in the future. Since there is still no cure for cSVD, modifiable confounding factors should be studied more intensively in the future to maintain or promote brain health and thus cognitive abilities in older adults.

Keywords:  Brain Health; Cerebral Small Vessel Disease; Entorhinal Cortical Thickness; Leisure Activity; Longitudinal Analysis; Memory Performance

DOI:  https://doi.org/10.1016/j.neuroimage.2023.120461
Mol Reprod Dev. 2023 Nov 24.

Epigenetic aging of mammalian gametes.

Michael Klutstein, Nitzan Gonen.

  The process of aging refers to physiological changes that occur to an organism as time progresses and involves changes to DNA, proteins, metabolism, cells, and organs. Like the rest of the cells in the body, gametes age, and it is well established that there is a decline in reproductive capabilities in females and males with aging. One of the major pathways known to be involved in aging is epigenetic changes. The epigenome is the multitude of chemical modifications performed on DNA and chromatin that affect the ability of chromatin to be transcribed. In this review, we explore the effects of aging on female and male gametes with a focus on the epigenetic changes that occur in gametes throughout aging. Quality decline in oocytes occurs at a relatively early age. Epigenetic changes constitute an important part of oocyte aging. DNA methylation is reduced with age, along with reduced expression of DNA methyltransferases (DNMTs). Histone deacetylases (HDAC) expression is also reduced, and a loss of heterochromatin marks occurs with age. As a consequence of heterochromatin loss, retrotransposon expression is elevated, and aged oocytes suffer from DNA damage. In sperm, aging affects sperm number, motility and fecundity, and epigenetic changes may constitute a part of this process. 5 methyl-cytosine (5mC) methylation is elevated in sperm from aged men, but methylation on Long interspersed nuclear elements (LINE) elements is reduced. Di and trimethylation of histone 3 lysine 9 (H3K9me2/3) is reduced in sperm from aged men and trimethylation of histone 3 lysine 27 (H3K27me3) is elevated. The protamine makeup of sperm from aged men is also changed, with reduced protamine expression and a misbalanced ratio between protamine proteins protamine P1 and protamine P2. The study of epigenetic reproductive aging is recently gaining interest. The current status of the field suggests that many aspects of gamete epigenetic aging are still open for investigation. The clinical applications of these investigations have far-reaching consequences for fertility and sociological human behavior.

Keywords:  DNA methylation; aging; epigenetic modifications; gametes; oocytes; sperm

DOI:  https://doi.org/10.1002/mrd.23717
Geroscience. 2023 Nov 21.

Heterogeneity of increased biological age in type 2 diabetes correlates with differential tissue DNA methylation, biological variables, and pharmacological treatments.

Briana N Cortez, Hui Pan, Samuel Hinthorn, Han Sun, Nicola Neretti, Anna L Gloyn, Cristina Aguayo-Mazzucato.

  Biological age (BA) closely depicts age-related changes at a cellular level. Type 2 diabetes mellitus (T2D) accelerates BA when calculated using clinical biomarkers, but there is a large spread in the magnitude of individuals' age acceleration in T2D suggesting additional factors contributing to BA. Additionally, it is unknown whether BA can be changed with treatment. We hypothesized that potential determinants of the heterogeneous BA distribution in T2D could be due to differential tissue aging as reflected at the DNA methylation (DNAm) level, or biological variables and their respective therapeutic treatments. Publicly available DNAm samples were obtained to calculate BA using the DNAm phenotypic age (DNAmPhenoAge) algorithm. DNAmPhenoAge showed age acceleration in T2D samples of whole blood, pancreatic islets, and liver, but not in adipose tissue or skeletal muscle. Analysis of genes associated with differentially methylated CpG sites found a significant correlation between eight individual CpG methylation sites and gene expression. Clinical biomarkers from participants in the NHANES 2017-2018 and ACCORD cohorts were used to calculate BA using the Klemera and Doubal (KDM) method. Cardiovascular and glycemic biomarkers associated with increased BA while intensive blood pressure and glycemic management reduced BA to CA levels, demonstrating that accelerated BA can be restored in the setting of T2D.

Keywords:  Biological aging; Type 2 diabetes

DOI:  https://doi.org/10.1007/s11357-023-01009-8
JAMA Netw Open. 2023 Nov 01. 6(11): e2344186

Food Insecurity, Memory, and Dementia Among US Adults Aged 50 Years and Older.

Haobing Qian, Aayush Khadka, Suzanna M Martinez, Sonali Singh, Willa D Brenowitz, Adina Zeki Al Hazzouri, Tanisha G Hill-Jarrett, M Maria Glymour, Anusha M Vable.

Importance: Despite existing federal programs to increase access to food, food insecurity is common among US older adults. Food insecurity may affect Alzheimer disease and Alzheimer disease-related dementias via multiple mechanisms, yet there is almost no quantitative research evaluating this association.
Objective: To examine whether food insecurity in older adults is associated with later-life cognitive outcomes.
Design, Setting, and Participants: This cohort study of US residents aged 50 years and older from the US Health and Retirement Study was restricted to respondents with food insecurity data in 2013 and cognitive outcome data between calendar years 2014 and 2018. Analyses were conducted from June 1 to September 22, 2023.
Exposure: Food insecurity status in 2013 was assessed using the validated US Department of Agriculture 6-item Household Food Security Module. Respondents were classified as being food secure, low food secure, and very low food secure.
Main Outcomes and Measures: Outcomes were dementia probability and memory score (standardized to 1998 units), estimated biennially between 2014 and 2018 using a previously validated algorithm. Generalized estimation equations were fit for dementia risk and linear mixed-effects models for memory score, taking selective attrition into account through inverse probability of censoring weights.
Results: The sample consisted of 7012 participants (18 356 person-waves); mean (SD) age was 67.7 (10.0) years, 4131 (58.9%) were women, 1136 (16.2%) were non-Hispanic Black, 4849 (69.2%) were non-Hispanic White, and mean (SD) duration of schooling was 13.0 (3.0) years. Compared with food-secure older adults, experiencing low food security was associated with higher odds of dementia (odds ratio, 1.38; 95% CI, 1.15-1.67) as was experiencing very low food security (odds ratio, 1.37; 95% CI, 1.11-1.59). Low and very low food security was also associated with lower memory levels and faster age-related memory decline.
Conclusions and Relevance: In this cohort study of older US residents, food insecurity was associated with increased dementia risk, poorer memory function, and faster memory decline. Future studies are needed to examine whether addressing food insecurity may benefit brain health.

DOI: https://doi.org/10.1001/jamanetworkopen.2023.44186
medRxiv. 2023 Nov 06. pii: 2023.11.05.23298134. [Epub ahead of print]

Associations of Objective and Self-Reported Physical Activity and Sedentary Behavior with Skeletal Muscle Energetics: The Study of Muscle, Mobility and Aging (SOMMA).

Yujia Susanna Qiao, Terri L Blackwell, Peggy M Cawthon, Paul M Coen, Steven R Cummings, Giovanna Distefano, Samaneh Farsijani, Daniel E Forman, Bret H Goodpaster, Stephen B Kritchevsky, Theresa Mau, Frederico G S Toledo, Anne B Newman, Nancy W Glynn.

Background: Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to counteract these declines in older adults. Yet, many studies were based on self-reported PA or structured exercise interventions. We examined the associations of objective daily PA and sedentary behavior (SB) with skeletal muscle energetics and also compared with self-reported PA and SB. We also explored the extent to which PA would attenuate the associations of age with muscle energetics.
Methods: Among the Study of Muscle, Mobility and Aging (SOMMA) enrolled older adults, 810 (mean age=76±5, 58% women) had maximal muscle oxidative capacity measured ex vivo via high-resolution respirometry of permeabilized myofibers (maxOXPHOS) and in vivo by 31 Phosphorus magnetic resonance spectroscopy (ATP max ). Objective PA was measured using the wrist-worn ActiGraph GT9X over 7-days to capture sedentary behavior (SB), light, and moderate-to-vigorous PA (MVPA). Self-reported SB, MVPA, and all exercise-related PA were assessed with The Community Healthy Activities Model Program for Seniors questionnaire. Linear regression models with progressive covariate adjustments evaluated the associations between SB, PA and muscle energetics, and the attenuation of the age / muscle energetic association by PA.
Results: Every 30 minutes more objective MVPA was associated with 0.65 pmol/s*mg higher maxOXPHOS and 0.012 mM/sec higher ATP max , after adjustment for age, site/technician and sex. More time spent in objective light+MVPA was significantly associated with higher ATP max , but not maxOXPHOS. In contrast, every 30 minutes spent in objective SB was associated with 0.43 pmol/s*mg lower maxOXPHOS and 0.004 mM/sec lower ATP max . Only associations with ATP max held after further adjusting for socioeconomic status, body mass index, lifestyle factors and multimorbidities. Self-reported MVPA and all exercise-related activities, but not SB, yielded similar associations with maxOXPHOS and ATP max . Lastly, age was only significantly associated with muscle energetics in men. Adjusting for objective time spent in MVPA attenuated the age association with ATP max by nearly 60% in men.
Conclusion: More time spent in daily PA, especially MVPA, were associated with higher muscle energetics. Interventions that increase higher intensity activity might offer potential therapeutic interventions to slow the age-related decline in muscle energetics. Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.

DOI: https://doi.org/10.1101/2023.11.05.23298134
Lancet. 2023 Nov;pii: S0140-6736(23)02137-2. [Epub ahead of print]402 Suppl 1 S49

More play and fewer screens: a way to improve preschoolers' mental health? Cross-sectional findings from the British Preschool-children's Play Survey.

Kathryn R Hesketh, Helen F Dodd.

BACKGROUND: Children increasingly engage in more screentime and less play. Concurrently, 10% of UK children now have a diagnosable mental health condition. Adventurous play (ie, thrilling and exciting play, likely inducing fear or uncertainty) might prevent mental health problems but is unexplored in preschoolers. We assessed the association between mental health and both adventurous play and screentime, hypothesising that more adventurous play and less screentime would be associated with better mental health.
METHODS: This cross-sectional study used data from a nationally representative sample of caregivers of children aged 2-4 years. Participants were recruited through YouGov in February 2023 and gave informed consent (Cambridge University Ethics HSSREC.22·312). We derived three behavioural exposures and four mental health outcomes from parent-report. Exposures were time (in h/week) a child spent playing adventurously, looking at a screen for educational purposed, and looking at a screen for recreational purposes. Outcomes were: internalising and externalising score from the Strengths and Difficulties Questionnaire (SDQ) and positive and negative affect scores from the Positive and Negative Affect Schedule for Children-P (PANAS). We conducted linear regression to explore associations between the three behavioural exposures and four mental health outcomes. We also tested for interactions between adventurous play and each screentime. We adjusted for child and parental demographic variables, using a Bonferroni-corrected α (0·0125).
FINDINGS: Care-givers of 1079 children provided valid data for all variables (age 2: n=319 [30%], age 3: 384 [36%], age 4: 376 [35%]; female n=517 [48%], male n=562 [52%]; white: n=878 [81%], mixed ethnicity: n=80 [7%], other: n=221 [11%]). For each additional hour per week a children engaged in adventurous play, they had lower internalising (β -0·02, 95% CI -0·03 to -0·00) and externalising (-0·02, -0·03 to -0·00) scores, and higher positive affect (0·06, 0·05 to 0·08). Compared with 0-2 h/week of educational screentime, longer educational screentime was associated with higher internalising scores (4-6 h: 1·42, 0·62 to 2·21; ≥6 h: 2·56, 1·40 to 3·72) and negative affect (4-6 h: 1·54, 0·84 to 2·23; ≥6 h: 2·17, 0·88 to 3·46). Recreational screentime was not associated with outcomes. No significant interactions were identified.
INTERPRETATION: Adventurous play was associated with better mental health, whereas high educational screentime was associated with poorer mental health; although effect sizes were small. Consistent with research in older children, associations with positive affect were stronger than mental health symptoms. No significant effect of recreational screentime was found, possibly due to underreporting, as it might be deemed less socially desirable than educational screentime, where effects were seen. Reliance on parental-report remains a limitation of this study. Nevertheless, this is the first work to demonstrate that diverse play opportunities for preschools, including taking risks, might be important for their mental health.
FUNDING: Wellcome Trust and the Medical Research Council.

DOI: https://doi.org/10.1016/S0140-6736(23)02137-2
medRxiv. 2023 Nov 07. pii: 2023.11.06.23298173. [Epub ahead of print]

Lower Physical Activity Modifies the Association between Perceived Fatigability and Executive Function but not Memory: The Study of Muscle, Mobility and Aging (SOMMA).

Benjamin T Schumacher, Caterina Rosano, Yujia Susanna Qiao, Andrea L Rosso, Peggy M Cawthon, Kyle D Moored, Steven R Cummings, Stephen B Kritchevsky, Nancy W Glynn.

OBJECTIVE: Emerging evidence shows that perceived fatigability-the quantification of vulnerability to fatigue in relation to specific intensity and duration of activities-may be associated with cognitive function. We sought to quantify associations with multiple domains of cognitive function and the role of physical activity (PA).
METHODS: SOMMA participants completed the Pittsburgh Fatigability Scale (PFS) Physical and Mental subscales (each range 0-50; higher scores=greater fatigability) and three cognitive function assessments [Digit Symbol Substitution Test (DSST), executive function; Montreal Cognitive Assessment (MoCA), general function; and California Verbal Learning Test (CVLT), memory]. Linear regression quantified associations cross-sectionally between each PFS subscale and cognitive assessment scores adjusting for covariates. Effect modification by volume and intensity of accelerometer-measured PA was assessed.
RESULTS: In 873 participants (59.2% women; age 76.3±5.0; 85% White), mean PFS Physical, Mental, and DSST scores were 15.8±8.7, 7.7±7.8, and 55.4±13.7. After adjustments, for each 4-point higher PFS Physical and 3-point higher PFS Mental, participants had nearly one fewer correct DSST items [β coefficient and 95% confidence interval for PFS Physical: -0.69 (-1.09, - 0.29); PFS Mental: -0.64 (-0.97, -0.30)]. Volume and intensity of PA modified the association of PFS Mental and DSST ( P interactions <0.01). All associations were strongest in those with the lowest volume and intensity of PA. PFS was not associated with MoCA or CVLT.
DISCUSSION: Greater perceived fatigability may be associated with poorer executive function, but not memory. Individuals with greater perceived fatigability, particularly those less active, might benefit from interventions that reduce fatigability and may beneficially influence cognitive function.

DOI: https://doi.org/10.1101/2023.11.06.23298173
Psychoneuroendocrinology. 2023 Nov 20. pii: S0306-4530(23)00648-0. [Epub ahead of print]160 106670

Educational patterning in biological health seven years apart: Findings from the Tromsø Study.

Lola Neufcourt, Raphaële Castagné, Tom Wilsgaard, Sameline Grimsgaard, Marc Chadeau-Hyam, Dragana Vuckovic, Ainhoa Ugarteche-Perez, Erlend Hoftun Farbu, Torkjel M Sandanger, Cyrille Delpierre, Michelle Kelly-Irving.

   BACKGROUND: Social-to-biological processes is one set of mechanisms underlying the relationship between social position and health. However, very few studies have focused on the relationship between social factors and biology at multiple time points. This work investigates the relationship between education and the dynamic changes in a composite Biological Health Score (BHS) using two time points seven years apart in a Norwegian adult population.
METHODS: We used data from individuals aged 30 years and above who participated in Tromsø6 (2007-2008) and Tromsø7 (2015-2016) (n = 8117). BHS was defined using ten biomarkers measured from blood samples and representing three physiological systems (cardiovascular, metabolic, inflammatory). The higher the BHS, the poorer the health status.
FINDINGS: Linear regression models carried out on BHS revealed a strong educational gradient at two distinct time points but also over time. People with lower educational attainment were at higher risk of poor biological health at a given time point (βlow education Tromsø6=0.30 [95 %-CI=0.18-0.43] and βlow education Tromsø7=0.30 [95 %-CI=0.17-0.42]). They also presented higher longitudinal BHS compared to people with higher education (βlow education = 0.89 [95 %-CI=0.56-1.23]). Certain biomarkers related to the cardiovascular system and the metabolic system were strongly socially distributed, even after adjustment for sex, age, health behaviours and body mass index.
CONCLUSION: This longitudinal analysis highlights that participants with lower education had their biological health deteriorated to a greater extent over time compared to people with higher education. Our findings provide added evidence of the biological embodiment of social position, particularly with respect to dynamic aspects for which little evidence exists.

Keywords:  Allostatic load; Biomarkers; Health inequalities; Social embedding; Tromsø Study

DOI:  https://doi.org/10.1016/j.psyneuen.2023.106670
Biogerontology. 2023 Nov 21.

Telomere shortening induces aging-associated phenotypes in hiPSC-derived neurons and astrocytes.

Jasmine Harley, Munirah Mohamad Santosa, Chong Yi Ng, Oleg V Grinchuk, Jin-Hui Hor, Yajing Liang, Valerie Jingwen Lim, Wee Wei Tee, Derrick Sek Tong Ong, Shi-Yan Ng.

  Telomere shortening is a well-established hallmark of cellular aging. Telomerase reverse transcriptase (TERT) plays a crucial role in maintaining the length of telomeres, which are specialised protective caps at the end of chromosomes. The lack of in vitro aging models, particularly for the central nervous system (CNS), has impeded progress in understanding aging and age-associated neurodegenerative diseases. In this study, we aimed to explore the possibility of inducing aging-associated features in cell types of the CNS using hiPSC (human induced pluripotent stem cell) technology. To achieve this, we utilised CRISPR/Cas9 to generate hiPSCs with a loss of telomerase function and shortened telomeres. Through directed differentiation, we generated motor neurons and astrocytes to investigate whether telomere shortening could lead to age-associated phenotypes. Our findings revealed that shortened telomeres induced age-associated characteristics in both motor neurons and astrocytes including increased cellular senescence, heightened inflammation, and elevated DNA damage. We also observed cell-type specific age-related morphology changes. Additionally, our study highlighted the fundamental role of TERT and telomere shortening in neural progenitor cell (NPC) proliferation and neuronal differentiation. This study serves as a proof of concept that telomere shortening can effectively induce aging-associated phenotypes, thereby providing a valuable tool to investigate age-related decline and neurodegenerative diseases.

Keywords:  Aging; Astrocytes; Neurons; Telomerase reverse transcriptase; Telomeres; hiPSC

DOI:  https://doi.org/10.1007/s10522-023-10076-5
Int J Mol Sci. 2023 Nov 16. pii: 16406. [Epub ahead of print]24(22):

Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood.

Adriana Koller, Claudia Lamina, Caroline Brandl, Martina E Zimmermann, Klaus J Stark, Hansi Weissensteiner, Reinhard Würzner, Iris M Heid, Florian Kronenberg.

  Mitochondrial dysfunction is a common occurrence in the aging process and is observed in diseases such as age-related macular degeneration (AMD). Increased levels of reactive oxygen species lead to damaged mitochondrial DNA (mtDNA), resulting in dysfunctional mitochondria, and, consequently, mtDNA causes further harm in the retinal tissue. However, it is unclear whether the effects are locally restricted to the high-energy-demanding retinal pigment epithelium or are also systematically present. Therefore, we measured mtDNA copy number (mtDNA-CN) in peripheral blood using a qPCR approach with plasmid normalization in elderly participants with and without AMD from the AugUR study (n = 2262). We found significantly lower mtDNA-CN in the blood of participants with early (n = 453) and late (n = 170) AMD compared to AMD-free participants (n = 1630). In regression analyses, we found lower mtDNA-CN to be associated with late AMD when compared with AMD-free participants. Each reduction of mtDNA-CN by one standard deviation increased the risk for late AMD by 24%. This association was most pronounced in geographic atrophy (OR = 1.76, 95% CI 1.19-2.60, p = 0.004), which has limited treatment options. These findings provide new insights into the relationship between mtDNA-CN in blood and AMD, suggesting that it may serve as a more accessible biomarker than mtDNA-CN in the retina.

Keywords:  age-related macular degeneration; aging; geographic atrophy; mitochondrial DNA copy number; mtDNA abundance

DOI:  https://doi.org/10.3390/ijms242216406
Lancet. 2023 Nov;pii: S0140-6736(23)02147-5. [Epub ahead of print]402 Suppl 1 S83

Dose-response of accelerometer-measured physical activity, step count, and cancer risk in the UK Biobank: a prospective cohort analysis.

Alaina H Shreves, Scott R Small, Ruth C Travis, Charles E Matthews, Aiden Doherty.

BACKGROUND: Cancer is an age-related condition, but changes to modifiable lifestyle-related behaviours, including physical activity, could impact risk. While step count is an accessible metric of activity for older adults, its association with cancer risk remains poorly understood. We investigated the association between accelerometer-measured total activity, step count, and cancer risk.
METHODS: We analysed data from a prospective UK Biobank cohort of consenting participants who wore wrist-based Axivity AX3 accelerometer devices for 7 days between June 1, 2013 and Dec 23, 2015, had valid accelerometer data, and no previous cancer diagnosis at baseline. Machine learning models estimated total physical activity (vector magnitude) and step count. The primary outcome, a composite of 13 cancers previously associated with physical activity, was obtained from national registries. Hazard ratios (HR) and were calculated using Cox proportional hazard models, with attained age as the underlying timescale and adjustment for sex, ethnicity, smoking status, alcohol consumption, education, and Townsend Deprivation Index. The impact of reallocating time between behaviours was evaluated using compositional data analyses. Dose-response associations were assessed with restricted cubic splines.
FINDINGS: We analysed data from 86 556 participants, who were followed up during an average of 6·1 years (age range 43-78; 48 478 [56%] female and 38 078 [44%] male; 83 830 [97%] white). 5577 incident malignant cancers occurred among these 86 556 participants. Greater total physical activity was associated with a lower risk of physical-activity-related cancer (HR per 1 SD [+8·33 milligravity per day] 0·85, 95% CI 0·81-0·89). Reallocating 30 min/day from other activities to moderate-to-vigorous physical activity behaviour was associated with lower cancer risk (HR 0·96, 0·94-0·98), as was reallocating 1 h/day to light intensity activity (HR 0·94, 0·92-0·96), compared with the mean behaviour composition among included participants. Compared with taking 5000 steps per day, taking 10 000 daily steps was associated with a significantly lower risk of physical-activity-related cancer (HR 0·81, 0·73-0·90).
INTERPRETATION: In this sample from the UK Biobank, higher total physical activity and daily step count were associated with lower risk of physical-activity-related cancers. Findings suggest additional physical activity time, irrespective of intensity, may be beneficial. Increasing low intensity activity time and increasing daily step counts could be practical public health interventions to lower cancer risk, especially for aging adults.
FUNDING: National Institute of Health Oxford Cambridge Scholars Program, Wellcome Trust, Swiss Re, Health Data Research UK, and Cancer Research UK.

DOI: https://doi.org/10.1016/S0140-6736(23)02147-5
J Hum Hypertens. 2023 Nov 20.

Influence of blood pressure polygenic risk scores and environmental factors on coronary artery disease in the Korean Genome and Epidemiology Study.

Kyungsook Woo, Ji Eun Lim, Eun Young Lee.

The present study aimed to investigate the association of blood pressure polygenic risk scores (BP PRSs) with coronary artery disease (CAD) in a Korean population and the interaction effects between PRSs and environmental factors on CAD. Data were derived from the Cardiovascular Disease Association Study (CAVAS; N = 5100) and the Health Examinee Study (HEXA; N = 58,623) within the Korean Genome and Epidemiology Study. PRSs for systolic and diastolic BP were calculated with the weighted allele sum of >200 single-nucleotide polymorphisms. Multivariable logistic regression models were used. BP PRSs were strongly associated with systolic BP (SBP), diastolic BP (DBP), and hypertension in both CAVAS and HEXA (p < 0.0001). PRSSBP was significantly associated with CAD in CAVAS, while PRSSBP and PRSDBP were significantly associated with CAD in HEXA. There was an interaction effect between the BP PRSs and environmental factors on CAD. The odds ratios (ORs) for CAD were 1.036 (95% confidence interval [CI], 1.016-1.055) for obesity, 1.028 (95% CI, 1.011-1.045) for abdominal obesity, 1.030 (95% CI, 1.009-1.050) for triglyceride, 1.024 (95% CI, 1.008-1.041) for high-density lipoprotein cholesterol, and 1.039 for smoking (95% CI, 1.003-1.077) in CAVAS. There was no significant interaction in HEXA, except between PRSDBP and triglyceride (OR, 1.012; 95% CI, 1.001-1.024). BP PRS was associated with an increased risk of hypertension and CAD. The interactions among PRSs and environmental risk factors increased the risk of CAD. Multi-component interventions to lower BP in the population via healthy behaviors are needed to prevent CAD regardless of genetic predisposition.

DOI: https://doi.org/10.1038/s41371-023-00878-y
JAMA Netw Open. 2023 Nov 01. 6(11): e2344015

Deficit Accumulation Index and Biological Markers of Aging in Survivors of Childhood Cancer.

AnnaLynn M Williams, Jeanne S Mandelblatt, Mingjuan Wang, Qian Dong, Gregory T Armstrong, Nickhill Bhakta, Tara M Brinkman, Matthew J Ehrhardt, Daniel A Mulrooney, Nikesha Gilmore, Leslie L Robison, Yutaka Yasui, Brent J Small, Deokumar Srivastava, Melissa M Hudson, Kirsten K Ness, Kevin R Krull, Zhaoming Wang.

Importance: Survivors of childhood cancer experience premature aging compared with community controls. The deficit accumulation index (DAI) uses readily available clinical data to measure physiological age in survivors; however, little data exist on how well deficit accumulation represents underlying biological aging among survivors of cancer.
Objective: To examine the associations between the DAI and epigenetic age acceleration (EAA) and mean leukocyte telomere length (LTL).
Design, Setting, and Participants: This cross-sectional study analyzed data from the St Jude Lifetime Cohort, an assessment of survivors of childhood cancer who were treated at St Jude Children's Research Hospital in Memphis, Tennessee. Data were collected between 2007 and 2016, assayed between 2014 and 2019, and analyzed between 2022 and 2023. Participants were adult survivors who were diagnosed between 1962 and 2012 and who survived 5 years or more from time of diagnosis. The analyses were restricted to survivors with European ancestry, as there were too few survivors with non-European ancestry.
Exposures: The DAI included 44 aging-related items, such as chronic health conditions and functional, psychosocial, and mental well-being. Item responses were summed and divided by the total number of items, resulting in a ratio ranging from 0 to 1. These DAI results were categorized based on reported associations with hospitalization and mortality: low, defined as a DAI less than 0.2; medium, defined as a DAI of 0.2 to less than 0.35; and high, defined as a DAI of 0.35 or higher.
Main Outcomes and Measures: Genome-wide DNA methylation was generated from peripheral blood mononuclear cell-derived DNA. The EAA was calculated as the residuals from regressing the Levine epigenetic age on chronological age. The mean LTL was estimated using whole-genome sequencing data.
Results: This study included 2101 survivors of childhood cancer (1122 males [53.4%]; mean [SD] age, 33.9 [9.1] years; median [IQR] time since diagnosis, 25.1 [18.7-31.9] years) with European ancestry. Compared with survivors in the low DAI group, those in the high DAI group experienced 3.7 more years of EAA (β = 3.66; 95% CI, 2.47-4.85; P < .001), whereas those in the medium DAI group experienced 1.8 more years of EAA (β = 1.77; 95% CI, 0.84-2.69; P < .001), independent of treatment exposures. The EAA and DAI association was consistent across 3 common diagnoses (acute lymphoblastic leukemia, Hodgkin lymphoma, and central nervous system tumors) and across chronological age groups. For example, among acute lymphoblastic leukemia survivors, those in the medium DAI group (β = 2.27; 95% CI, 0.78-3.76; P = .001) experienced greater EAA vs those in the low DAI group. Similarly, among survivors younger than 30 years, the high DAI group experienced 4.9 more years of EAA vs the low DAI group (β = 4.95; 95% CI, 2.14-7.75; P < .001). There were no associations between mean LTL residual and the DAI.
Conclusions and Relevance: This cross-sectional study of survivors of childhood cancer showed that the DAI was associated with EAA, suggesting an underlying biological process to the accumulation of deficits. Both the DAI and EAA were effective at identifying aging phenotypes, and either may be used to measure aging and response to interventions targeting aging pathways.

DOI: https://doi.org/10.1001/jamanetworkopen.2023.44015
Lancet. 2023 Nov;pii: S0140-6736(23)02091-3. [Epub ahead of print]402 Suppl 1 S41

Moderating effect of country-level health determinants on the association between hobby engagement and mental health: cross-cohort multi-level models, meta-analyses, and meta-regressions.

Daisy Fancourt, Taiji Noguchi, Jessica K Bone, Jacques Wels, Qian Gao, Katsunori Kondo, Tami Saito, Hei Wan Mak.

BACKGROUND: Theories from anthropology, evolutionary psychology, and sociology have focused on the potential adaptive benefits of hobby engagement for mental health in older adults. However, previous studies have used data from single countries, potentially biased by specific measurement and methodological approaches, cohort effects, or cultural specificities. Whether there are genuine benefits for mental health in older adults cross-culturally remains unknown. This study explored the consistency of this association across 16 different nations.
METHODS: For this epidemiological study, we used data from adults aged 65 years or older across 16 countries in the USA, Europe, and Asia, represented in five longitudinal studies (ELSA, JAGES, HRS, SHARE and CHARLS; N=93 263, 45-62% female, mean age 72-76 years, data collected 2008-20). We harmonised measures of self-reported engagement in hobbies and past-times, depressive symptoms (validated scales), and Likert scale responses for self-reported health, happiness, and life satisfaction. We conducted fixed-effects models and longitudinal regression models of hobbies and mental health for each country and then pooled in multinational meta-analyses. We accounted for all time-constant factors including those unobserved (eg, genetics, past leisure behaviour, medical history, psychological traits) and identified time-varying factors (eg, sociodemographic background, clinical conditions, daily functioning). We tested the potential moderating effects of country-level determinants of health in meta-regressions and multilevel models.
FINDINGS: Meta-analytic fixed-effects findings showed that having a hobby was associated with fewer depressive symptoms (pooled coefficient -0·10, 95% CI -0·13 to -0·07, I2=69·5%, H2=3·28), and higher levels of self-reported health (0·06, 0·03 to 0·08, I2=48·1%, H2=1·93), happiness (0·09, 0·06 to 0·13, I2=67·0%, H2=3·03), and life satisfaction (0·10, 0·08 to 0·12, I2=33·6%, H2=1·51). Results were consistent in meta-analyses of longitudinal regression models testing directionality of findings. Macro-level factors such as life expectancy, world happiness index, country wealth, and income inequality predicted prevalence of hobby engagement, but they showed only marginal moderating effects on the association between hobbies and mental health.
INTERPRETATION: Despite some heterogeneity in measurement between the cohorts, the apparent universality of the health benefits of hobbies internationally suggests that facilitating greater opportunities for engagement across demographic groups and between countries could be an important part of multidisciplinary care. Findings have implications for social prescribing schemes (currently in trial in many countries) and multidisciplinary work on origins and human behavioural patterns of hobby engagement.
FUNDING: National Endowment for the Arts, Wellcome Trust, Belgian Nnational Scientific Fund (FNRS).

DOI: https://doi.org/10.1016/S0140-6736(23)02091-3
Soc Sci Med. 2023 Nov 15. pii: S0277-9536(23)00776-1. [Epub ahead of print]340 116419

Social connectedness, functional capacity, and longevity: A focus on positive relations with others.

Elliot Friedman, Melissa Franks, Elizabeth Teas, Patricia A Thomas.

   RATIONALE: A large literature links social connectedness to health, but there is growing recognition of considerable nuance in the ways social connectedness is defined, assessed, and associated with health.
OBJECTIVE: This study centers on positive relations with others - a measure derived from philosophical notions of the components of a "good life" - and the extent to which it predicts functional limitations and mortality using data from the national, longitudinal Mid-Life in the United States (MIDUS) study. We also assess whether these associations are independent of two common measures of social connectedness: social integration and social support.
METHODS: Data on social connectedness came from the first wave of MIDUS (1994-1996), self-reported functional limitations were from the first (MIDUS 1) and third (MIDUS 3; 2013-2014) waves, and mortality data through 2022 were obtained from the National Death Index.
RESULTS: Linear regression analyses showed that higher scores on positive relations with others predicted significantly less increase in functional limitations over time, and logistic regression models showed reduced probability of onset of functional limitations between MIDUS 1 and MIDUS 3 in those scoring higher on positive relations with others. Mortality was also significantly lower in those with higher scores on positive relations with others. All models adjusted for demographic and health characteristics, and all associations were robust to the inclusion of social integration and social support in the models.
CONCLUSIONS: These results show that positive relations with others, a component of a well-lived life that describes sustained investment in social relationships that are mutual and trusting, is associated with two key health outcomes in aging adults: functional limitations and longevity. That these associations are independent of social integration and social support suggests a unique role for this formulation of social connectedness in the health of aging adults.

Keywords:  Aging; Functional limitations; Mortality; Positive relations with others; Social connectedness; Social integration; Social support

DOI:  https://doi.org/10.1016/j.socscimed.2023.116419
J Geriatr Psychiatry Neurol. 2023 Nov 22. 8919887231218087

Association Between Mid-arm Muscle Circumference and Cognitive Function: A Longitudinal Study of Chinese Adults.

Hillary B Spangler, David H Lynch, Annie Green Howard, Hsiao-Chuan Tien, Shufa Du, Bing Zhang, Huijun Wang, Penny Gordon Larsen, John A Batsis.

   BACKGROUND: Dementia affects 55 million people worldwide and low muscle mass may be associated with cognitive decline. Mid-arm muscle circumference (MAMC) correlates with dual-energy Xray absorptiometry and bioelectrical impedance analyses, yet are not routinely available. Therefore, we examined the association between MAMC and cognitive performance in older adults.
METHODS: We included community-dwelling adults ≥55 years from the China Health and Nutrition Survey. Cognitive function was estimated based on a subset of the modified Telephone Interview for Cognitive Status (0-27, low-high) during years (1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, 2018). A multivariable linear mixed-effects model was used to test whether MAMC was associated with rate of cognitive decline across age groups and cognitive function overall.
RESULTS: Of 3702 adults (53% female, 63.2 ± 7.3 years), mean MAMC was 21.4 cm ± 3.0 and baseline cognitive score was 13.6 points ±6.6. We found no evidence that the age-related rate of cognitive decline differed by MAMC (P = .77). Declines between 5-year age groups ranged from -.80 [SE (standard error) .18] to -1.09 [.22] for those at a mean MAMC, as compared to -.86 [.25] to -1.24 [.31] for those at a 1 MAMC 1 standard deviation above the mean. Higher MAMC was associated with better cognitive function with .13 [.06] higher scores for each corresponding 1 standard deviation increase in MAMC across all ages.
CONCLUSION: Higher MAMC at any age was associated with better cognitive performance in older adults. Understanding the relationship between muscle mass and cognition may identify at-risk subgroups needing targeted interventions to preserve cognition.

Keywords:  cognitive decline; dementia; geriatrics

DOI:  https://doi.org/10.1177/08919887231218087
Am J Alzheimers Dis Other Demen. 2023 Jan-Dec;38:38 15333175231214833

Music Engagement as a Source of Cognitive Reserve.

Lee Wolff, Yixue Quan, Gemma Perry, William Forde Thompson.

  Music engagement is a ubiquitous activity that is thought to have cognitive benefits for the rapidly aging population. In the absence of robust treatment approaches for many age-related and neuropathological health issues, interest has emerged surrounding lifestyle-enriching activities, like exercise and music engagement, to build cognitive reserve across the lifespan and preserve neurocognitive function in older adults. The present review evaluates evidence of neurocognitive preservation arising from lifelong music engagement with respect to the cognitive reserve hypothesis. We collated a body of neuroimaging, behavioral and epidemiological evidence to adjudicate the benefits of music engagement for cognitive reserve. The findings suggest that music engagement should be considered in tandem with other well-established cognitive reserve proxies as a contributor to differential clinical outcomes in older populations at risk of age-related and neuropathological cognitive decline.

Keywords:  Alzheimer disease; cognitive aging; cognitive reserve; dementia; healthy aging; music; neurodegenerative diseases

DOI:  https://doi.org/10.1177/15333175231214833
Biology (Basel). 2023 Nov 02. pii: 1396. [Epub ahead of print]12(11):

The Skin and Inflamm-Aging.

Rashi Agrawal, Anne Hu, Wendy B Bollag.

  With its unique anatomical location facing both the external and internal environment, the skin has crucial functions, including shielding the body from damage caused by ultraviolet radiation and chemicals, preventing water loss, acting as a primary barrier against pathogens, participating in metabolic processes like vitamin D production and temperature control and relaying information to the body through sensory and proprioceptor nerves. Like all organ systems, skin is known to undergo multiple changes with aging. A better understanding of the mechanisms that mediate aging-related skin dysfunction may allow the creation of targeted therapeutics that have beneficial effects not only on aged skin but also on other organs and tissues that experience a loss of or decline in function with aging. The skin is the largest organ of the body and can contribute to serum inflammatory mediator levels. One alteration known to occur with age is an impairment of skin barrier function; since disruption of the barrier is known to induce inflammation, skin may be a major contributor to the sustained, sub-clinical systemic inflammation associated with aging. Such "inflamm-aging" may underlie many of the deleterious changes observed in aged individuals. This review explores the role of age-related skin changes, skin inflammation and inflamm-aging.

Keywords:  aging; atopic dermatitis; epidermal barrier; epidermis; inflammation; keratinocytes; psoriasis; skin; xerosis

DOI:  https://doi.org/10.3390/biology12111396
J Affect Disord. 2023 Nov 22. pii: S0165-0327(23)01436-2. [Epub ahead of print]

Evaluation of lifestyle and dietary inflammatory score and their relationship with the odds of depression, stress, and anxiety in adults living in Yazd, Iran; based on YaHS and TAMYZ cohort study.

Hadis Varaee, Masoud Mirzaei, Amin Salehi Abarghouei, Nastaran Ahmadi, Mahdieh Hosseinzadeh.

   BACKGROUND: Mental disorders such as depression, anxiety and stress are becoming more common worldwide. The aim of this study was to examine the relationship between dietary inflammations scores (DIS) and lifestyle inflammation scores (LIS) and the risk of depression, stress, and anxiety in a large sample of Iranian adults.
METHODS: This study was based on 5579 adults (20-70 years) who participated in the Yazd Health Study (YaHS). The DIS score was calculated from the intake of 19 food groups and the LIS score was derived from four components. Multivariable logistic regression models were used to estimate the odds ratio (ORs) and 95 % confidence interval (CI) of depression, stress, and anxiety across quartiles of DIS and LIS.
RESULTS: 2749 of the participants (46 % male) had anxiety, depression and stress. According to the adjusted model, there was a positive association between LIS and the risk of anxiety (OR: 1.23, 95 % CI: 1.01-1.49) and depression (OR: 1.39, 95 % CI: 1.14-1.69, P for trend: 0.03). However, there was no significant association between LIS and the risk of stress. There was also no significant association between DIS and the risk of anxiety, depression and stress.
CONCLUSIONS: This study demonstrated that higher LIS scores were associated with depression and anxiety. It is suggested that following a LIS that includes smoking status, physical activity, alcohol consumption, and body mass index as indicators of the inflammatory promoting lifestyle, may increase the risk of depression and anxiety.

Keywords:  Anxiety; Depression; Diet; Inflammation; Lifestyle; Stress

DOI:  https://doi.org/10.1016/j.jad.2023.11.069
Curr Biol. 2023 Nov 20. pii: S0960-9822(23)01274-5. [Epub ahead of print]33(22): R1166-R1172

The 'faulty male' hypothesis for sex-biased mutation and disease.

Matthew W Hahn, Yadira Peña-Garcia, Richard J Wang.

Biological differences between males and females lead to many differences in physiology, disease, and overall health. One of the most prominent disparities is in the number of germline mutations passed to offspring: human males transmit three times as many mutations as do females. While the classic explanation for this pattern invokes differences in post-puberty germline replication between the sexes, recent whole-genome evidence in humans and other mammals has cast doubt on this mechanism. Here, we review recent work that is inconsistent with a replication-driven model of male-biased mutation, and propose an alternative, 'faulty male' hypothesis. This model proposes that males are less able to repair and/or protect DNA from damage compared to females. Importantly, we suggest that this new model for male-biased mutation may also help to explain several pronounced differences between the sexes in cancer, aging, and DNA repair. Although the detailed contributions of genetic, epigenetic, and hormonal influences of biological sex on mutation remain to be fully understood, a reconsideration of the mechanisms underlying these differences will lead to a deeper understanding of evolution and disease.

DOI: https://doi.org/10.1016/j.cub.2023.09.028
Clin Nutr. 2023 Nov 15. pii: S0261-5614(23)00365-5. [Epub ahead of print]43(1): 1-10

Association of dietary inflammatory potential, dietary oxidative balance score and biological aging.

Xuanyang Wang, Shuvan Kumar Sarker, Licheng Cheng, Keke Dang, Jinxia Hu, Sijia Pan, Jia Zhang, Xiaoqing Xu, Ying Li.

   BACKGROUND & AIMS: The interaction between diet, inflammation, and oxidative stress significantly influences aging, but the available evidence has been limited. We evaluated potential associations of dietary inflammatory index (DII), dietary oxidative balance score (DOBS), and measures of biological aging.
METHODS: This cross-sectional study was performed among 8839 individuals from NHANES 2003-2014. DII and DOBS were determined by aggregating data from 26 to 17 a priori selected dietary components. Biological aging metrics included homeostatic dysregulation (HD), Klemera-Doubal method (KDM), phenotypic age (PA), and allostatic load (AL). Binomial logistic regression models and multivariate linear regression models were conducted.
RESULTS: The associations of dietary inflammation and oxidative stress potential and biological aging metrics were significant among American adults nationwide. Consuming foods with higher DII was significantly associated with accelerated HD 1.26 (1.10, 1.44), KDM 1.24 (1.06, 1.45), and PA 1.54 (1.33, 1.78). Compared with the lowest DOBS, the hazard ratios of accelerated HD, KDM, PA, and AL were 0.74 (0.64, 0.86), 0.80 (0.70, 0.92), 0.61 (0.52, 0.72) and 0.78 (0.63, 0.97), respectively. The adverse effects of pro-inflammatory and pro-oxidative diets on accelerated HD, KDM, and PA were 1.39 (1.18, 1.62), 1.28 (1.08, 1.51), and 1.76 (1.47, 2.10). Serum AST/ALT ratio and globulin were implicated in and mediate the aging effects.
CONCLUSIONS: Higher DII and/or lower DOBS are associated with higher markers of biological aging. Our research elucidates that diets may mitigate biological aging resulting from inflammation and/or oxidative stress.

Keywords:  Biological age; Diet; Inflammation; National health and nutrition examination survey (NHANES); Oxidative stress

DOI:  https://doi.org/10.1016/j.clnu.2023.11.007
Int J Mol Sci. 2023 Nov 17. pii: 16469. [Epub ahead of print]24(22):

The Molecular Role of Polyamines in Age-Related Diseases: An Update.

Guadalupe Elizabeth Jimenez Gutierrez, Fabiola V Borbolla Jiménez, Luis G Muñoz, Yessica Sarai Tapia Guerrero, Nadia Mireya Murillo Melo, José Melesio Cristóbal-Luna, Norberto Leyva Garcia, Joaquín Cordero-Martínez, Jonathan J Magaña.

  Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high concentrations in a wide variety of organisms and tissues, suggesting that they play an important role in cellular physiology. Polyamines include spermine, spermidine, and putrescine, which play important roles in age-related diseases that have not been completely elucidated. Aging is a natural process, defined as the time-related deterioration of the physiological functions; it is considered a risk factor for degenerative diseases such as cardiovascular, neurodegenerative, and musculoskeletal diseases; arthritis; and even cancer. In this review, we provide a new perspective on the participation of Pas in the cellular and molecular processes related to age-related diseases, focusing our attention on important degenerative diseases such as Alzheimerߣs disease, Parkinsonߣs disease, osteoarthritis, sarcopenia, and osteoporosis. This new perspective leads us to propose that Pas function as novel biomarkers for age-related diseases, with the main purpose of achieving new molecular alternatives for healthier aging.

Keywords:  age-related diseases; aging; aging biomarkers; polyamines; putrescine; spermidine; spermine

DOI:  https://doi.org/10.3390/ijms242216469
Aging Clin Exp Res. 2023 Nov 24.

Causal relationship between depression and aging: a bidirectional two-sample Mendelian randomization study.

Xinxin Luo, Zhichao Ruan, Ling Liu.

   BACKGROUND: The causal relationship and the direction of the effect between depression and aging remain controversial.
METHODS: We used a bidirectional two-sample Mendelian randomization analysis to examine the relationship between depression and age proxy indicators. We obtained pooled statistics from genome-wide association studies (GWAS) on depression and the age proxy indicators. We employed five MR analysis methods to address potential biases and ensure robustness of our results, with the inverse variance weighted (IVW) method being the primary outcome. We also conducted outlier exclusion using Radial MR, MRPRESSO, and MR Steiger filters. Additionally, sensitivity analyses were performed to assess heterogeneity and pleiotropy.
RESULTS: Our MR analysis revealed that depression causally leads to shortened telomere length (β = - 0.014; P = 0.038), increased frailty index (β = 0.076; P = 0.000), and accelerated GrimAge (β = 0.249; P = 0.024). Furthermore, our findings showed that the frailty index (OR = 1.679; P = 0.001) was causally associated with an increased risk of depression. Additionally, we found that appendicular lean mass (OR = 0.929; P = 0.000) and left-hand grip strength (OR = 0.836; P = 0.014) were causally associated with a reduced risk of depression. Sensitivity analyses demonstrated the robustness of our findings.
CONCLUSIONS: Our study provides evidence that depression contributes to the accelerated aging process, resulting in decreased telomere length, increased frailty index, and accelerated GrimAge. Additionally, we found that the frailty index increases the risk of depression, while appendicular lean mass and left-handed grip strength reduce the risk of depression.

Keywords:  Aging; Depression; Epigenetic age; Mendelian randomization; Telomere length

DOI:  https://doi.org/10.1007/s40520-023-02596-4
Br J Nutr. 2023 Nov 22. 1-21

Association of Diet Quality with Hand Grip Strength Weakness and Asymmetry in A Multi-ethnic Asian Cohort.

Jiannan Huang, Aarathi Shanmugam, Xiangyuan Huang, Rob M van Dam, Saima Hilal.

  Hand grip strength (HGS) is an important diagnostic tool for sarcopenia and a reliable predictor for age-related chronic diseases and mortality. Interventions in nutrition have been shown as a low-cost strategy to maintain muscular strength and mass. However, there are limited data on the effect of diet on HGS in Southeast Asian populations. This study aims to investigate the association of diet quality with HGS weakness and asymmetry in a multi-ethnic population in Singapore. This cross-sectional study used data from the Singapore Multi-Ethnic Cohort (n=1,547). Dietary data were collected using a validated semi-quantitative food frequency questionnaire and summarized as the Dietary Quality Index - International (DQI-I). HGS was calculated as the maximum value of six measurements from both hands. HGS weakness and asymmetry were defined using well-recognized criteria. Multivariable linear regression and logistic regression were utilized for continuous and binary outcomes respectively, adjusting for age, sex, ethnicity, physical activity, and smoking status. It was found that the highest quartile of DQI-I was significantly associated with higher HGS (β=1.11; 95%CI: 0.41, 1.82; p-trend<0.001), and lower odds of HGS asymmetry (OR=0.71; 95%CI: 0.53, 0.94; p-trend=0.035) and both HGS weakness and asymmetry (OR=0.50; 95%CI: 0.32, 0.76; p-trend=0.004). Among the different components of DQI-I, only dietary adequacy was significantly associated with higher HGS (p-trend<0.001) and lower odds for both HGS weakness and asymmetry (p-trend=0.006). Our findings support that DQI-I, an indicator of overall diet quality, can be used to provide dietary guidelines for prevention and management of muscle wasting, sarcopenia, and frailty.

Keywords:  Asia; diet quality; grip strength; multi-ethnic population; sarcopenia

DOI:  https://doi.org/10.1017/S0007114523002647
Lancet. 2023 Nov;pii: S0140-6736(23)02129-3. [Epub ahead of print]402 Suppl 1 S48

Social determinants of mental health trajectories during midlife: a prospective British birth cohort study.

Christoph Henking, Dawid Gondek.

BACKGROUND: There is an ongoing debate about whether mental wellbeing follows a U-shaped pattern across the lifespan, with a universal low point during midlife. However, existing research largely looks at average distributions of mental health problems and does not consider the underlying trajectories and social determinants. We investigate the social factors linked to changes in mental health during midlife.
METHODS: For this prospective observational study, we used representative data from the 1970 British Cohort Study for the ages 34, 42, and 46-48 years (N=8581, 51·5% female, 48·5% male; born in the same week in 1970) to identify participants with declining mental health in midlife, and then used logistic regressions to determine what social factors (eg, education and employment status) were associated with this decline. Mental health was measured using the short version of the Malaise Inventory (scored 0-9). Using the cutoff point of 4 (indicating high risk of depression), we categorised participants who changed from below the cutoff to above the cutoff from age 34 to 46 years as "declining mental health" (as opposed to "stable" and "improved" mental health who were grouped together into one category). All analyses controlled for sex and parental socioeconomic status.
FINDINGS: Of the participants who responded to all mental health questions, 5302 (82·2%) remained stable, 429 (6·7%) had improved, and 671 (10·5%) had declining mental health. Our logistic regressions show that university education was linked to a lower risk of declining mental health controlled for sex and parental socioeconomic status odds ratio [OR] 0·79, 95% CI 0·85-0·94; controlling for sex and parental socioeconomic status). Experiencing unemployment during this period was linked to a higher risk of declining mental health (OR 1·75, 1·24-2·42), whereas people with permanent or temporary sickness or disability were three times more likely to experience a deterioration of mental health compared with those in full-time employment (OR 3·12, 2·46-3·93).
INTERPRETATION: The midlife decline in mental health might not be a universal phenomenon, but it might rather be influenced by social factors and changes in people's lives. Individuals experiencing unemployment, particularly those excluded from the labour market, are at a considerably higher risk of experiencing a decline in mental health. This is study provides only descriptive evidence and should be followed up by causal analyses.
FUNDING: Economic and Social Research Council (ESRC).

DOI: https://doi.org/10.1016/S0140-6736(23)02129-3