Organ-specific biological clocks: Ageotyping for personalized anti-aging medicine

Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102253 - 102253

Опубликована: Март 4, 2024

Aging is a complex multidimensional, progressive remodeling process affecting multiple organ systems. While many studies have focused on studying aging across organs, assessment of the contribution individual organs to overall processes cutting-edge issue. An organ's biological age might influence other revealing multiorgan network. Recent data demonstrated similar yet asynchronous inter-organs and inter-individuals progression aging, thereby providing foundation track sources declining health in old age. The integration omics with common clinical parameters through artificial intelligence has allowed building organ-specific clocks, which can predict development specific age-related diseases at high resolution. peculiar aging-trajectory, referred as ageotype, provide novel tool for personalized anti-aging, preventive medicine. Here, we review relative clocks omics-based data, suggesting different rates. Additional research longitudinal including young subjects analyzing sex-related differences, should be encouraged apply ageotyping analysis purposes practice.

Язык: Английский

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Sex and education differences in trajectories of physiological ageing: longitudinal analysis of a prospective English cohort study

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Physiological age (PA) derived from clinical indicators including blood-based biomarkers and tests of physiological function can be compared with chronological to examine disparities in health between older adults the same age. Though education interacts sex lead inequalities healthy ageing, their combined influence on longitudinally-measured PA has not been explored. We based examined how interact inform trajectories. Three waves (2004/05-2012/13) drawn English Longitudinal Study Ageing (ages 50-100 years) were used estimate PA, which was internally validated by confirming associations incident chronic conditions, functional limitations, memory impairment after adjustment for sex. Joint models construct trajectories 8,891 ELSA participants educational PA. Among least educated participants, there negligible differences until 60 (sex difference [men-women] 50=-0.6 years [95% confidence interval=-2.2-0.6]; 60=0.4 [-0.6-1.4]); at 70, women 1.5 (0.7-2.2) than men. most 3.8 (1.6-6.0) younger men 50, 2.7 (0.4-5.0) 60, a non-significant 70. Higher provides larger midlife buffer ageing Policies promote gender equity higher may contribute improving women's across range ageing-related outcomes.

Язык: Английский

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Stability of Aging‐ and Cognition‐Related Methylation Profile Scores Across Two Waves in Children and Adolescents

Child Development, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

DNA-methylation profile scores (MPSs) index biology relevant for lifelong physical and cognitive health, but information on their longitudinal stability in childhood is lacking. Using two waves of data collected from 2014 to 2022 (Mlag between = 2.41 years) N 407 participants (Mage 12.05 years, 51% female, 60% White), test-retest correlations were estimated four salivary MPSs related aging (PhenoAgeAccel, GrimAgeAccel, DunedinPACE), function (Epigenetic-g). varied (test-retest rs 0.38 0.76). did not differ children exposed the COVID-19 pandemic, race-ethnic sex differences apparent. Further research necessary understand which environmental perturbations impact trajectories when are most sensitive those impacts.

Язык: Английский

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Association between epigenetic age and type 2 diabetes mellitus or glycemic traits: A longitudinal twin study

Aging Cell, Год журнала: 2024, Номер 23(7)

Опубликована: Апрель 25, 2024

Abstract Epigenetic clocks based on DNA methylation have been known as biomarkers of aging, including principal component (PC) representing the degree aging and DunedinPACE pace aging. Prior studies shown associations between epigenetic T2DM, but results vary by age metrics people. This study explored T2DM or glycemic traits, 1070 twins (535 twin pairs) from Chinese National Twin Registry. It also temporal relationships traits in 314 (157 who participated baseline follow‐up visits after a mean 4.6 years. data were used to calculate metrics, PCGrimAge acceleration (PCGrimAA), PCPhenoAge (PCPhenoAA), DunedinPACE, longitudinal change rate PCGrimAge/PCPhenoAge. Mixed‐effects cross‐lagged modelling assessed cross‐sectional respectively. In analysis, positive identified well PCPhenoAA fasting plasma glucose, which may be not confounded shared genetic factors. Cross‐lagged models revealed that (fasting HbA1c, TyG index) preceded increases, index PCGrimAA increases. Glycemic are positively associated with especially DunedinPACE. increases PCGrimAA. Lowering levels reduce PCGrimAA, thereby mitigating age‐related comorbidities.

Язык: Английский

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Socioeconomic Status, Lifestyle, and DNA Methylation Age Among Racially and Ethnically Diverse Adults

JAMA Network Open, Год журнала: 2024, Номер 7(7), С. e2421889 - e2421889

Опубликована: Июль 29, 2024

Importance Variation in DNA methylation at specific loci estimates biological age, which is associated with morbidity, mortality, and social experiences. Aging known as epigenetic clocks, including the Dunedin Pace of Calculated From Epigenome (DunedinPACE), were trained on data predominately from individuals European ancestry; however, limited research has explored DunedinPACE underrepresented populations experiencing health disparities. Objective To investigate associations neighborhood individual sociobehavioral factors aging a racially ethnically diverse population. Design, Setting, Participants This cohort study, part Multiethnic Cohort study conducted May 1993 to September 1996 examine racial ethnic disparities chronic diseases, integrated biospecimen self-reported collected between April 2004 November 2005 healthy Hawaii residents aged 45 76 years. These participants self-identified Japanese American, Native Hawaiian, or White background. Data analyzed January 2022 2024. Main Outcomes Measures generated monocytes enriched cryopreserved lymphocytes used derive scores 2017 June 2021. Neighborhood economic status (NSES) was estimated 1990 US Census Bureau include such educational level, occupation, income. Individual-level included body mass index (BMI), physical activity (PA), diet quality measured by Healthy Eating Index (HEI). Linear regression analysis their NSES variables. Results A total 376 (113 [30.1%] 144 [38.3%] 119 [31.6%] White; 189 [50.3%] female). Mean (SE) age 57.81 (0.38) Overall, mean significantly higher among females than males (1.28 [0.01] vs 1.25 [0.01]; P = .005); correlated negatively ( R −0.09; .08), HEI −0.11; .03), attainment −0.15; .003) positively BMI 0.31; < .001); varied race ethnicity. Hawaiian exhibited score (1.31 [0.01]) compared American (1.25 .001) (1.22 participants. Controlling for sex, HEI, BMI, NSES, linear analyses revealed negative association level (β, −0.005 [95% CI, −0.013 0.002]; .03) −0.003 −0.011 0.005]; .08) participants, yet this positive 0.007; 95% −0.001 0.015; .09). Moderate vigorous PA lower only −0.006; −0.001; .005), independent NSES. Conclusions Relevance In sample adults, low rate score, individual-level affected association, findings support interventions addressing inequities.

Язык: Английский

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Intrinsic capacity and recent falls in adults 80 years and older living in the community: results from the ilSIRENTE Study

Aging Clinical and Experimental Research, Год журнала: 2024, Номер 36(1)

Опубликована: Авг. 10, 2024

Abstract Background Falls in older adults significantly impact overall health and healthcare costs. Intrinsic capacity (IC) reflects functional reserve is an indicator of healthy aging. Aims To explore the association between IC recent falls (≤ 90 days) community-dwelling octogenarians from Aging Longevity Sirente geographic area (IlSIRENTE) study. Methods The Minimum Data Set for Home Care (MDS−HC) supplementary questionnaires tests were used to assess five domains: locomotion, cognition, vitality, psychology, sensory. Scores each domain rescaled using percent maximum possible score method averaged obtain (range 0−100). Results study included 319 participants (mean age 85.5 ± 4.8 years, 67.1% women). Mean was 80.5 14.2. optimal cut-off predicting two-year risk incident loss at least one activity daily living (ADL) determined validated a subset 240 individuals without ADL disability baseline 84.7 4.4 Participants then stratified into low (< 77.6) high (≥ categories. Those with (63.9%) younger, more often males, had lower prevalence falls, disability, multimorbidity, polypharmacy. Logistic regression models including as continuous variable revealed significant higher odds falls. This unadjusted (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94–0.98, p < 0.001), age- sex-adjusted (OR CI fully adjusted 0.93–0.99, = 0.003). When considering categorical variable, logistic showed strong 0.31, 0.16–0.60, 0.001). remained both 0.30, 0.15–0.59, 0.001) 0.33, 0.16–0.82, 0.007). locomotion independently associated 0.98, 0.97–0.99, 0.97, 0.96–0.99, model Discussion first MDS−HC-derived instrument IC. Individuals less likely report being domain. Conclusions Lower linked increased Interventions maintain improve IC, especially domain, may reduce fall octogenarians.

Язык: Английский

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Demographic characteristics and epigenetic biological aging among post-9/11 veterans: Associations of DunedinPACE with sex, race, and age

Psychiatry Research, Год журнала: 2024, Номер 336, С. 115908 - 115908

Опубликована: Апрель 10, 2024

Язык: Английский

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Epigenetic age acceleration and the risk of frailty, and persistent activities of daily living (ADL) disability

Age and Ageing, Год журнала: 2024, Номер 53(6)

Опубликована: Июнь 1, 2024

Abstract Background Epigenetic ageing is among the most promising biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) associated with change in frailty scores over 7 years 7-year risk incident persistent Activities Daily Living (ADL) disability 560 Australians (50.7% females) aged ≥70 years. Methods Seven AA indices, including GrimAge, GrimAge2, FitAge DunedinPACE, were estimated from baseline peripheral-blood DNA-methylation. Frailty was assessed using both 67-item deficit-accumulation index (FI) Fried phenotype (Fried). Persistent ADL defined as loss ability to perform one or more basic ADLs for at least 6 months. Linear mixed models Cox proportional-hazard regression used appropriate. Results Accelerated DunedinPACE increasing FI per year (adjusted-Beta ranged 0.0015 0.0021, P &lt; 0.05), accelerated GrimAge GrimAge2 an increased FI-defined (adjusted-HRs 1.43 1.39, respectively, 0.05). The association between stronger females 0.0029, 0.001 than males 0.0002, 0.81). but not other measures, also worsening 0.0175, 0.04). No associations observed disability. Conclusion later life frailty.

Язык: Английский

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Disentangling the effect of sex from brain size on brain organization and cognitive functioning

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Язык: Английский

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Association of plasma biomarkers of Alzheimer’s pathology and neurodegeneration with gait performance in older adults

Communications Medicine, Год журнала: 2025, Номер 5(1)

Опубликована: Янв. 16, 2025

Declining gait performance is seen in aging individuals, due to neural and systemic factors. Plasma biomarkers provide an accessible way assess evolving brain changes; non-specific neurodegeneration (NfL, GFAP) or Alzheimer's disease (Aβ 42/40 ratio, P-Tau181). In a population-based cohort of older adults, we evaluate the hypothesis that plasma Disease pathology are associated with worse performance. A sample 2641 Mayo Clinic Study Aging participants measurements parameters was analyzed this cross-sectional study. Linear regression models using as predictors adjusted for age, sex, BMI, Charlson Comorbidity Index, cognitive diagnosis were evaluated. study multiple statistically significant relationships observed GFAP, NfL, P-Tau181 parameters. Each standard deviation increase reduction velocity 2.100 (95% CI: -3.004, -1.196; p = 5.4 × 10-6), 4.400 (-5.292, -3.507; 9.5 10-22), 2.617 (-3.414, -1.819; 1.5 10-10) cm/sec, respectively. Overall, NfL has strongest associations poor Models age interactions show strength between became stronger increasing age. There no specific associate individual biomarkers. not only markers decline but also indicate motor population.

Язык: Английский

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