Plasma proteomic signature of the risk of developing mobility disability: A 9‐year follow‐up

Osawa, Yusuke; Semba, Richard D.; Fantoni, Giovanna; Candia, Julián; Biancotto, Angélique; Tanaka, Toshiko; Bandinelli, Stefania; Ferrucci, Luigi

doi:10.1111/acel.13132

Cited by 39 publications

(30 citation statements)

References 43 publications

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“…There is growing evidence in both human and animal models that GDF15 plays an important role beyond cardiovascular disease and has been linked with weight homeostasis, fibrosis, diabetes, cardiovascular disease, renal disease, mobility disability and cancer (27)(28)(29)(30)(31)(32). IL-6, a classical SASP factor in multiple senescent cell types (19), was also associated with allcause mortality.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, GDF15 has been suggested as a biomarker of cardiovascular disease mortality, but more recently associated with all-cause mortality ( Lindholm et al, 2018 ; ActiFE study group et al, 2019 ). There is growing evidence in both human and animal models that GDF15 plays an important role beyond cardiovascular disease and has been linked to weight homeostasis, fibrosis, diabetes, cardiovascular disease, renal disease, mobility disability and cancer ( Baek and Eling, 2019 ; Bidadkosh et al, 2017 ; Daniels et al, 2011 ; Ho et al, 2013 ; Wallentin et al, 2013 ; Osawa et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Plasma proteomic biomarker signature of age predicts health and life span

Tanaka

Basisty

Fantoni

et al. 2020

eLife

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104

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Older age is a strong shared risk factor for many chronic diseases and there is increasing interest in identifying aging biomarkers. Here a proteomic analysis of 1301 plasma proteins was conducted in 997 individuals between 21 and 102 years of age. We identified 651 proteins associated with age (506 over-represented, 145 underrepresented with age) was identified. Mediation analysis suggested a role for partial cis-epigenetic control of protein expression with age. Of the age-associated proteins, 33.5% and 45.3%, were associated with mortality and multimorbidity, respectively. There was enrichment of proteins associated with inflammation and extracellular matrix as well as senescence-associated secretory proteins. A 76-protein proteomic age signature predicted accumulation of chronic diseases and all-cause mortality. These data support the premise of proteomic biomarkers to monitor aging trajectories and to identify individuals at higher risk for disease to be targeted for in depth diagnostic procedures and early interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasma proteomic biomarker signature of age predicts health and life span

Tanaka

Basisty

Fantoni

et al. 2020

eLife

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104

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“…Noteworthy, after the 5-year follow-up, more than half of the participants with ≥2 nutritional deficits became octogenarians whose mobility tends to decline faster than in younger people ( 17 ). On the other hand, our exploratory analysis found that LGI, an important mechanism implicated in both aging ( 37 ) and mobility disability ( 17 , 38 ), contributed to this accelerated decline of physical performance in older individuals with combined nutritional deficits. This finding suggests that both the presence of nutritional deficits and chronic inflammation contribute to physical impairment.…”

Section: Discussionmentioning

confidence: 81%

Associations Between Nutritional Deficits and Physical Performance in Community-Dwelling Older Adults

Giudici

Rolland

et al. 2021

Front. Nutr.

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Background: Whether multiple nutritional deficiencies have a synergic effect on mobility loss remains unknown. This study aims to evaluate associations between multi-nutritional deficits and physical performance evolution among community-dwelling older adults.Methods: We included 386 participants from the Multidomain Alzheimer Preventive Trial (MAPT) (75.6 ± 4.5 years) not receiving omega-3 polyunsaturated fatty acid (PUFA) supplementation and who had available data on nutritional deficits. Baseline nutritional deficits were defined as plasma 25 hydroxyvitamin D <20 ng/ml, plasma homocysteine >14 μmol/L, or erythrocyte omega-3 PUFA index ≤ 4.87% (lower quartile). The Short Physical Performance Battery (SPPB), gait speed, and chair rise time were used to assess physical performance at baseline and after 6, 12, 24, 36, 48, and 60 months. We explored if nutrition-physical performance associations varied according to the presence of low-grade inflammation (LGI) and brain imaging indicators.Results: Within-group comparisons showed that physical function (decreased SPPB and gait speed, increased chair rise time) worsened over time, particularly in participants with ≥2 nutritional deficits; however, no between-group differences were observed when individuals without deficit and those with either 1 or ≥2 deficits were compared. Our exploratory analysis on nutritional deficit-LGI interactions showed that, among people with ≥2 deficits, chair rise time was increased over time in participants with LGI (adjusted mean difference: 3.47; 95% CI: 1.03, 5.91; p = 0.017), compared with individuals with no LGI.Conclusions: Accumulated deficits on vitamin D, homocysteine, and omega-3 PUFA were not associated with physical performance evolution in older adults, but they determined declined chair rise performance in subjects with low-grade inflammation.Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT00672685], identifier [NCT00672685].

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“…Similar to what has been done with the methylome, elastic regression or other multivariate methods can be used to compute a weighted average of protein concentrations that approximate chronological aging and show deviation from chronological aging in individuals in a trajectory of deteriorating health (Lehallier et al, 2019;Tanaka et al, 2020a). Studies are ongoing to identify proteins that in asymptomatic individuals predict the development of phenotypes typical of aging, such dementia (Tanaka et al, 2020b), frailty (Landino et al, 2020) and many other diseases (Osawa et al, 2020;Tanaka et al, 2020b).…”

Section: The Rationale For Using Proteomics In Building System Models In Humansmentioning

confidence: 99%

Proteomics and Epidemiological Models of Human Aging

et al. 2021

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Human aging is associated with a decline of physical and cognitive function and high susceptibility to chronic diseases, which is influenced by genetics, epigenetics, environmental, and socio-economic status. In order to identify the factors that modulate the aging process, established measures of aging mechanisms are required, that are both robust and feasible in humans. It is also necessary to connect these measures to the phenotypes of aging and their functional consequences. In this review, we focus on how this has been addressed from an epidemiologic perspective using proteomics. The key aspects of epidemiological models of aging can be incorporated into proteomics and other omics which can provide critical detailed information on the molecular and biological processes that change with age, thus unveiling underlying mechanisms that drive multiple chronic conditions and frailty, and ideally facilitating the identification of new effective approaches for prevention and treatment.

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Plasma proteomic signature of the risk of developing mobility disability: A 9‐year follow‐up

Cited by 39 publications

References 43 publications

Plasma proteomic biomarker signature of age predicts health and life span

Plasma proteomic biomarker signature of age predicts health and life span

Associations Between Nutritional Deficits and Physical Performance in Community-Dwelling Older Adults

Proteomics and Epidemiological Models of Human Aging

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