Dataset Information

Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging.

ABSTRACT: In defiance of the paradigm that calories from all sources are equivalent, we and others have shown that dietary protein is a dominant regulator of healthy aging. The restriction of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan when initiated in young or adult mice. However, many interventions are less efficacious or even deleterious when initiated in aged animals. Here, we investigate the physiological, metabolic, and molecular consequences of consuming a diet with a 67% reduction of all amino acids (Low AA), or of isoleucine alone (Low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. We find that both diet regimens effectively reduce adiposity and improve glucose tolerance, which were benefits that were not mediated by reduced calorie intake. Both diets improve specific aspects of frailty, slow multiple molecular indicators of aging rate, and rejuvenate the aging heart and liver at the molecular level. These results demonstrate that Low AA and Low Ile diets can drive youthful physiological and molecular signatures, and support the possibility that these dietary interventions could help to promote healthy aging in older adults.

SUBMITTER: Yeh CY

PROVIDER: S-EPMC9934591 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging.

Yeh Chung-Yang CY Chini Lucas C S LCS Davidson Jessica W JW Garcia Gonzalo G GG Gallagher Meredith S MS Freichels Isaac T IT Calubag Mariah F MF Rodgers Allison C AC Green Cara L CL Babygirija Reji R Sonsalla Michelle M MM Pak Heidi H HH Trautman Michaela M Hacker Timothy A TA Miller Richard A RA Simcox Judith J Lamming Dudley W DW

bioRxiv : the preprint server for biology 20240109

In defiance of the paradigm that calories from all sources are equivalent, we and others have shown that dietary protein is a dominant regulator of healthy aging. The restriction of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan when initiated in young or adult mice. However, many interventions are less efficacious or even deleterious when initiated in aged animals. Here, we investigate the physiological, metabolic, and molecular consequences of cons ...[more]

PMID: 36798157

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Project description:BackgroundThere is limited research examining the impact of risk and protective factors on late-life depression using large population-based datasets, particularly those examining differences among older migrants and non-migrants in Europe countries. Thus, the first aim was to analyze differences between migrants and non-migrants regarding socioeconomic status, depression, multimorbidity, healthy aging, and lifestyle behaviors. The second aim was to examine the impact of healthy aging on late-life depression in older migrants compared to their counterparts without a history of international migration in extensive and harmonized data from different population-based cohort studies.Materials and methodsWe analyzed cross-sectional, predominantly nationally representative, community-based data from European participants in the Aging Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) cohort. The descriptive analyses included sociodemographic variables, somatic comorbidities, multimorbidity, healthy aging, and lifestyle behaviors according to migration status. The effects of these variables on late-life depression were examined in a multivariate logistic regression model, including migration status and years since migration as predictors.ResultsData of 122,571 individuals aged ≥ 50 years were analyzed, of which 11,799 (9.60%) were migrants. The descriptive analyses indicated that compared to non-migrants, migrants showed a higher prevalence of diabetes (25.6%), hypertension (38.0%), coronary artery disease (49.4%), stroke (4.9%), and depression (31.1%). Healthy aging was also better in non-migrants (51.7; SD = 9.7) than in migrants (39.6; SD = 18.2). The results of the logistic regression showed that migration status [OR = 1.231 (CIs: 0.914-1.547)] and increased number of years since migration in the host country [OR = 0.003 (CIs: 0.001-0.005)] were associated with greater levels of depressive symptoms. Concerning health variables, multimorbidity was associated with higher levels of depressive symptoms [OR = 0.244 (CIs: 0.211-0.278)], whereas better healthy aging was associated with fewer depressive symptoms [OR = -0.100 (CIs: -0.102 to -0.098)]. The interaction between migration and healthy aging status was also significant [OR. = -0.019 (CIs: -0.025 to -0.014)].ConclusionMigrants reported higher risks for worse health outcomes compared to non-migrants. Significantly, worse healthy aging was associated with a greater risk of depressive symptoms in migrants than in non-migrants. Shedding light on migration and aging processes is essential for promoting a cross-cultural understanding of late-life depression in Europe.

Project description:ImportanceGenetic and lifestyle factors contribute to an individual's risk of developing Alzheimer's disease. However, it is unknown whether and how adherence to healthy lifestyles can mitigate the genetic risk of Alzheimer's.ObjectiveThe aim of this study is to investigate whether adherence to healthy lifestyles can modify the impact of genetic predisposition to Alzheimer's disease on later-life cognitive decline.Design setting and participantsThis prospective cohort study included 891 adults of European ancestry, aged 40 to 65, who were without dementia and had complete healthy-lifestyle and cognition data during the follow-up. Participants joined the Wisconsin Registry for Alzheimer's Prevention (WRAP) beginning in 2001. We conducted replication analyses using a subsample with similar baseline age range from the Health and Retirement Study (HRS).ExposuresWe assessed participants' exposures using a continuous non-APOE polygenic risk score for Alzheimer's, a binary indicator for APOE-ε4 carrier status, and a weighted healthy-lifestyle score, including factors such as no current smoking, regular physical activity, healthy diet, light to moderate alcohol consumption, and frequent cognitive activities.Main outcomes and measuresWe z-standardized cognitive scores for global (Preclinical Alzheimer's Cognitive Composite score 3 - PACC3) and domain-specific assessments (delayed recall and immediate learning).ResultsWe followed 891 individuals for up to 10 years (mean [SD] baseline age, 58 [6] years, 31% male, 38% APOE-ε4 carriers). After false discovery rate (FDR) correction, we found statistically significant PRS × lifestyle × age interactions on preclinical cognitive decline but the evidence is stronger among APOE-ε4 carriers. Among APOE-ε4 carriers, PRS-related differences in overall and memory-related domains between people scoring 0-1 and 4-5 regarding healthy lifestyles became evident around age 67 after FDR correction. These findings were robust across several sensitivity analyses and were replicated in the population-based HRS.ConclusionA favorable lifestyle can mitigate the genetic risk associated with current known non-APOE genetic variants for longitudinal cognitive decline, and these protective effects are particularly pronounced among APOE-ε4 carriers.

Dataset Information

Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging.

Publications

Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging.

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