Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy

Elliott, M.; Caspi, Avshalom; Houts, Renate; Ambler, Antony; Broadbent, Jonathan M.; Hancox, Robert J.; Harrington, HonaLee; Hogan, Sean; Keenan, Rāwiri; Leung, Joan; Melzer, Tracy R.; Purdy, Suzanne C.; Ramrakha, Sandhya; Richmond‐Rakerd, Leah S.; Righarts, Antoinette; Sugden, Karen; Thomson, William; Thorne, Peter R.; Williams, Benjamin; Wilson, Graham; Hariri, Ahmad R.; Poulton, Richie; Moffitt, Terrie E.

doi:10.1038/s43587-021-00044-4

Cited by 178 publications

(158 citation statements)

References 84 publications

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“…Variation in notional biological aging has been proposed to account for inter-individual differences in the way people age 40 . Combined with larger and more available datasets, machine learning methods can improve our understanding of brain function and our ability to predict health trajectories from brain properties.…”

Section: Discussionmentioning

confidence: 99%

Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease

et al. 2021

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Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18–94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology.

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Section: Discussionmentioning

confidence: 99%

Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease

et al. 2021

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“…With aging, the risk of both CKD and declining capacities such as reduced strength and cognition increases ( 40 ); this risk is maximized in subjects developing “accelerated biological aging” ( 41 ). Sensory–motor functioning is very common in frail individuals who are at highly vulnerable for loss of independence in activities of day living, fall and mortality ( 42 ). Since the population in the western countries aged > 65 is expected to rapidly increase in the next years ( 43 ), CKD and age-related losses in skeletal muscle function and mass are considered as an extremely important public health issue ( 44 ).…”

Section: Aging and Common Kidney Disease Comorbidities Which Impair Mpsmentioning

confidence: 99%

How to Overcome Anabolic Resistance in Dialysis-Treated Patients?

et al. 2021

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A current hypothesis is that dialysis-treated patients are “anabolic resistant” i. e., their muscle protein synthesis (MPS) response to anabolic stimuli is blunted, an effect which leads to muscle wasting and poor physical performance in aging and in several chronic diseases. The importance of maintaining muscle mass and MPS is often neglected in dialysis-treated patients; better than to describe mechanisms leading to energy-protein wasting, the aim of this narrative review is to suggest possible strategies to overcome anabolic resistance in this patient's category. Food intake, in particular dietary protein, and physical activity, are the two major anabolic stimuli. Unfortunately, dialysis patients are often aged and have a sedentary behavior, all conditions which per se may induce a state of “anabolic resistance.” In addition, patients on dialysis are exposed to amino acid or protein deprivation during the dialysis sessions. Unfortunately, the optimal amount and formula of protein/amino acid composition in supplements to maximixe MPS is still unknown in dialysis patients. In young healthy subjects, 20 g whey protein maximally stimulate MPS. However, recent observations suggest that dialysis patients need greater amounts of proteins than healthy subjects to maximally stimulate MPS. Since unneccesary amounts of amino acids could stimulate ureagenesis, toxins and acid production, it is urgent to obtain information on the optimal dose of proteins or amino acids/ketoacids to maximize MPS in this patients' population. In the meantime, the issue of maintaining muscle mass and function in dialysis-treated CKD patients needs not to be overlooked by the kidney community.

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“…Nevertheless, there is not a common patron of deterioration and some individuals may not ever decline, maintaining their abilities in a good condition [ 6 ]. This could be because chronological age may be a poor proxy for biological age [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Differences in Trajectories and Predictive Factors of Cognition over Time in a Sample of Cognitively Healthy Adults, in Zaragoza, Spain

Lobo

Gracia-García

Lobò

et al. 2021

IJERPH

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Great inter-individual variability has been reported in the maintenance of cognitive function in aging. We examined this heterogeneity by modeling cognitive trajectories in a population-based longitudinal study of adults aged 55+ years. We hypothesized that (1) distinct classes of cognitive trajectories would be found, and (2) between-class differences in associated factors would be observed. The sample comprised 2403 cognitively healthy individuals from the Zaragoza Dementia and Depression (ZARADEMP) project, who had at least three measurements of the Mini-Mental State Examination (MMSE) in a 12-year follow-up. Longitudinal changes in cognitive functioning were modeled using growth mixture models (GMM) in the data. The best-fitting age-adjusted model showed 3 distinct trajectories, with 1-high-to-moderate (21.2% of participants), 2-moderate-stable (67.5%) and, 3-low-and-declining (9.9%) cognitive function over time, respectively. Compared with the reference 2-trajectory, the association of education and depression was significantly different in trajectories 1 and 3. Instrumental activities of daily living (iADLs) were only associated with the declining trajectory. This suggests that intervention strategies should be tailored specifically to individuals with different trajectories of cognitive aging, and intervention strategies designed to maintain cognitive function might be different from those to prevent decline. A stable cognitive performance (‘successful cognitive aging’) rather than a mild decline, might be more ‘normal’ than generally expected.

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Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy

Cited by 178 publications

References 84 publications

Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease

Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease

How to Overcome Anabolic Resistance in Dialysis-Treated Patients?

Differences in Trajectories and Predictive Factors of Cognition over Time in a Sample of Cognitively Healthy Adults, in Zaragoza, Spain

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