Longitudinal trajectories of intrinsic capacity and their association with quality of life and disability

Salinas‐Rodríguez, Aarón; González-Bautista, Emmanuel; Rivera-Almaraz, Ana; Manrique‐Espinoza, Betty

doi:10.1016/j.maturitas.2022.02.005

Cited by 34 publications

(20 citation statements)

References 22 publications

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“…S1 Indeed, a lower IC predicts the onset of disability, 3 ,S2 institutionalization 3 and mortality 4 in older adults. Despite the fact that IC shows an overall declining trend, there is a wide variation in IC levels and decline rates among older individuals 3,5 . Heterogeneity in IC trajectories is possibly explained by individuals' variability in biological ageing.…”

Section: Introductionmentioning

confidence: 99%

Plasma inflammation‐related biomarkers are associated with intrinsic capacity in community‐dwelling older adults

González-Bautista

Guyonnet

et al. 2023

J cachexia sarcopenia muscle

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Background How inflammation relates to intrinsic capacity (IC), the composite of physical and mental capacities, remains undefined. Our study aimed to investigate the cross-sectional and longitudinal associations between plasma inflammation-related biomarkers and IC in older adults. Methods This secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) included 1238 communitydwelling older individuals with IC assessments from 12 to 60 months. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor receptor-1 (TNFR-1), monocyte chemoattractant protein-1 (MCP-1) and growth differentiation factor-15 (GDF-15) were measured at 12 months. IC was operationalized as a score ranging from 0 to 100, derived from four domains: cognition, Mini-Mental State Examination; locomotion, Short Physical Performance Battery; psychological, Geriatric Depression Scale; and vitality, handgrip strength. A five-domain IC score (plus sensory) was investigated in a subsample (n = 535) with a 1-year follow-up as an exploratory outcome. ResultsThe mean age of the 1238 participants was 76.2 years (SD = 4.3); 63.7% were female. Their initial four-domain IC scores averaged 78.9 points (SD = 9.3), with a yearly decline of 1.17 points (95% CI = À1.30 to À1.05; P < 0.001). We observed significant associations of lower baseline IC with higher CRP, IL-6, TNFR-1 and GDF-15, after controlling age, sex, MAPT group allocation and educational level [CRP: adjusted β (95% CI) = À1.56 (À2.64 to À0.48); P = 0.005; IL-6: adjusted β = À3.16 (À4.82 to À1.50); P < 0.001; TNFR-1: adjusted β = À6.86 (À10.25 to À3.47); P < 0.001; GDF-15: adjusted β = À7.07 (À10.02 to À4.12); P < 0.001]. Higher TNFR-1, MCP-1 and GDF-15 were associated with faster decline in four-domain IC over 4 years [TNFR-1: adjusted β (95% CI) = À1.28 (À2.29 to À0.27); P = 0.013; MCP-1: adjusted β = À1.33 (À2.24 to À0.42); P = 0.004; GDF-15: adjusted β = À1.42 (À2.26 to À0.58); P = 0.001]. None of the biomarkers was significantly associated with the five-domain IC decline. Conclusions Inflammation was associated with lower IC in older adults. Among all plasma biomarkers, TNFR-1 and GDF-15 were consistently associated with IC at the cross-sectional and longitudinal levels.

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Section: Introductionmentioning

confidence: 99%

Plasma inflammation‐related biomarkers are associated with intrinsic capacity in community‐dwelling older adults

González-Bautista

Guyonnet

et al. 2023

J cachexia sarcopenia muscle

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“…These observations, together with reports that various types of neuropsychiatric disorders are associated with increased risks of age‐related diseases (Goldstein et al, 2009), mortality (Diniz et al, 2014), and shortened telomeres (Kiecolt‐Glaser & Wilson, 2016), suggest that cellular senescence and premature aging may be important etiologies of brain disorders. In addition to age‐related brain disorders, increasing age is associated with impaired of cognitive abilities (Liu et al, 2015), which affect the quality of life, even for healthy people (Salinas‐Rodríguez et al, 2022). Very little is known about the mechanisms leading to neural cell senescence, age‐related cognitive disabilities, and neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to age-related brain disorders, increasing age is associated with impaired of cognitive abilities (Liu et al, 2015), which affect the quality of life, even for healthy people (Salinas-Rodríguez et al, 2022). Very little is known about the mechanisms leading to neural cell senescence, age-related cognitive disabilities, and neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Protein phosphatase 2A activators reverse age‐related behavioral changes by targeting neural cell senescence

et al. 2023

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The contribution of cellular senescence to the behavioral changes observed in the elderly remains elusive. Here, we observed that aging is associated with a decline in protein phosphatase 2A (PP2A) activity in the brains of zebrafish and mice. Moreover, drugs activating PP2A reversed age‐related behavioral changes. We developed a transgenic zebrafish model to decrease PP2A activity in the brain through knockout of the ppp2r2c gene encoding a regulatory subunit of PP2A. Mutant fish exhibited the behavioral phenotype observed in old animals and premature accumulation of neural cells positive for markers of cellular senescence, including senescence‐associated β‐galactosidase, elevated levels cdkn2a/b, cdkn1a, senescence‐associated secretory phenotype gene expression, and an increased level of DNA damage signaling. The behavioral and cell senescence phenotypes were reversed in mutant fish through treatment with the senolytic ABT263 or diverse PP2A activators as well as through cdkn1a or tp53 gene ablation. Senomorphic function of PP2A activators was demonstrated in mouse primary neural cells with downregulated Ppp2r2c. We conclude that PP2A reduction leads to neural cell senescence thereby contributing to age‐related behavioral changes and that PP2A activators have senotherapeutic properties against deleterious behavioral effects of brain aging.

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“…In the WHO Integrated Care for Older People, IC consists of five elements, i.e., locomotion, sensory, vitality, psychological, and cognition, which represent the physiological competence of individuals to support their FA [1]. Although there are strong theoretical and consensual bases to support this multidomain conceptualization of IC [5][6][7][8], most empirical studies have focused on the associations between IC and disability [4,9], falls [10], quality of life [11], and mortality [12][13][14]. Unique diet, lifestyle, culture and policy may interact with IC, and contribute to FA, particularly in Asia [8].…”

Section: Introductionmentioning

confidence: 99%

Intrinsic capacity differs from functional ability in predicting 10-year mortality and biological features in healthy aging: results from the I-Lan longitudinal aging study

Lee

Peng

Lin

et al. 2023

Aging

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This study aimed to explore the biological features and mortality risk of intrinsic capacity (IC) and functional ability (FA). Based on data from 1839 participants from the I-Lan Longitudinal Aging Study, multivariable Cox proportional hazard models were used to evaluate the predictive ability of IC (range 0-100) and FA (range 0-100) on 10-year mortality. Of 2038 repeated measurements for IC within a 7-year observational period, multivariable logistic regression was used to compare biological features of participants with maintained, improved and rapidly deteriorated IC. A 1-point increased IC value was associated with a 5% (HR 0.95, 95% CI 0.93-0.97, p < 0.001) decrease in mortality risk. Low IC (HR 1.94, 95% CI 1.39-2.70, p < 0.001) was associated with higher mortality risk. Hyperglycemia (OR 1.40, 95% CI 1.09-1.81, p = 0.010), low serum levels of DHEA-S (OR 3.33, 95% CI 1.32-8.41, p = 0.011), and high serum levels of C-reactive protein (OR 1.45, 95% CI 1.05-2.00, p = 0.023) were associated with low IC at baseline. Low serum levels of DHEA-S (middle tertile OR 1.84, 95% CI 1.15-2.95, p = 0.012; lowest tertile OR 2.25, 95% CI 1.34-3.77, p = 0.002) and vitamin D deficiency (OR 1.82, 95% CI 1.02-3.27, p = 0.044) were associated with rapid deterioration of IC. IC and FA predicted 10-year mortality, whereas chronic inflammation, hyperglycemia, and low DHEA-S were associated with low IC status. Low DHEA-S and vitamin D deficiency may be considered as potential biomarkers of rapid IC declines, which implies underlying biological mechanisms of healthy aging.

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Longitudinal trajectories of intrinsic capacity and their association with quality of life and disability

Cited by 34 publications

References 22 publications

Plasma inflammation‐related biomarkers are associated with intrinsic capacity in community‐dwelling older adults

Plasma inflammation‐related biomarkers are associated with intrinsic capacity in community‐dwelling older adults

Protein phosphatase 2A activators reverse age‐related behavioral changes by targeting neural cell senescence

Intrinsic capacity differs from functional ability in predicting 10-year mortality and biological features in healthy aging: results from the I-Lan longitudinal aging study

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