Inflammatory signatures in older persons with physical frailty and sarcopenia: The frailty “cytokinome” at its core

Marzetti, Emanuele; Picca, Anna; Marini, Federico; Biancolillo, Alessandra; Coelho-Júnior, Hélio José; Gervasoni, Jacopo; Bossola, Maurizio; Cesari, Matteo; Onder, Graziano; Landi, Francesco; Bernabei, Roberto; Calvani, Riccardo

doi:10.1016/j.exger.2019.04.019

Cited by 85 publications

(75 citation statements)

References 60 publications

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“…Recently, we described the existence of a frailty "cytokinome" in older adults with PF&S defined by higher levels of P-selectin, C-reactive protein, and interferon-γ-induced protein 10, and lower levels of myeloperoxidase, interleukin 8, monocyte chemoattractant protein-1, macrophage inflammatory protein 1-α, and platelet-derived growth factor BB [8]. Pro-sarcopenic/pro-disability effects have traditionally been attributed to inflammation [48,49] as much as to dysfunction of anti-inflammatory pathways [49,50].…”

Section: Discussionmentioning

confidence: 99%

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Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature

Picca

Beli

Calvani

et al. 2020

Cells

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Mitochondrial dysfunction and systemic inflammation are major factors in the development of sarcopenia, but the molecular determinants linking the two mechanisms are only partially understood. The study of extracellular vesicle (EV) trafficking may provide insights into this relationship. Circulating small EVs (sEVs) from serum of 11 older adults with physical frailty and sarcopenia (PF&S) and 10 controls were purified and characterized. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers, including adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), nicotinamide adenine dinucleotide reduced form (NADH):ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2) were quantified by Western immunoblotting. Participants with PF&S showed higher levels of circulating sEVs relative to controls. Protein levels of CD9 and CD63 were lower in the sEV fraction of PF&S older adults, while CD81 was unvaried between groups. In addition, circulating sEVs from PF&S participants had lower amounts of ATP5A, NDUFS3, and SDHB. No signal was detected for MTCOI, NDUFB8, or UQCRC2 in either participant group. Our findings indicate that, in spite of increased sEV secretion, lower amounts of mitochondrial components are discarded through EV in older adults with PF&S. In-depth analysis of EV trafficking might open new venues for biomarker discovery and treatment development for PF&S.

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Section: Discussionmentioning

confidence: 99%

“…The subset of participants included in the present study was representative of the whole BIOSPHERE cohort in terms of age, sex distribution, clinical characteristics, and body composition and functional parameters [8]. The main characteristics of study participants are presented in Table 2.…”

Section: Characteristics Of the Study Participantsmentioning

confidence: 99%

Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature

Picca

Beli

Calvani

et al. 2020

Cells

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“…Since markers pertaining to a single domain (e.g., inflammatory rather than metabolic) may fail at capturing the intertwined relationship between local and systemic changes, we decided to combine metabolomics analysis and immunoassays to characterize the metabolic and inflammatory profile of older adults with MCI. A biomarker panel has been designed based on previous investigations by our group in older populations, including older adults with neurodegenerative conditions [10,[38][39][40][41][42][43]. This approach was also guided by the recent advances made in the field of geroscience [67].…”

Section: Discussionmentioning

confidence: 99%

“…A biomarker panel has been designed based on previous investigations by our group in older populations, including older adults with neurodegenerative conditions [10,[38][39][40][41][42][43]. Markers of systemic inflammation will be assayed as described elsewhere [40].…”

Section: Determination Of Biomarkers Of Inflammation and Neurodegenermentioning

confidence: 99%

“…Multi-marker approaches covering different physiological domains are increasingly implemented for the appraisal of complex and dynamic conditions [9][10][11]. These approaches are conceptualized within the notion of allostatic load, that is the exposure of cells and biological systems to recurrent or chronic stressors inflicting cumulative damage [12].…”

Section: Introductionmentioning

confidence: 99%

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The “develOpment of metabolic and functional markers of Dementia IN Older people” (ODINO) Study: Rationale, Design and Methods

Picca

Ronconi

Coelho-Júnior

et al. 2020

JPM

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Mild cognitive impairment (MCI), also termed mild neurocognitive disorder, includes a heterogeneous group of conditions characterized by declines in one or more cognitive domains greater than that expected during "normal" aging but not severe enough to impair functional abilities. MCI has been associated with an increased risk of developing dementia and even considered an early stage of it. Therefore, noninvasively accessible biomarkers of MCI are highly sought after for early identification of the condition. Systemic inflammation, metabolic perturbations, and declining physical performance have been described in people with MCI. However, whether biological and functional parameters differ across MCI neuropsychological subtypes is presently debated. Likewise, the predictive value of existing biomarkers toward MCI conversion into dementia is unclear. The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) study was conceived as a multi-dimensional investigation in which multi-marker discovery will be coupled with innovative statistical approaches to characterize patterns of systemic inflammation, metabolic perturbations, and physical performance in older adults with MCI. The ultimate aim of ODINO is to identify potential biomarkers specific for MCI subtypes and predictive of MCI conversion into Alzheimer's disease or other forms of dementia over a three-year follow-up. Here, we describe the rationale, design, and methods of ODINO.

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Physical Function Trajectories and Mortality in Older Adults With Multisensory Impairment

Vohra,

Simonsick,

Kamath

et al. 2024

JAMA Otolaryngol Head Neck Surg

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ImportanceSingle sensory impairment is associated with reduced functional resilience and increased mortality, though the effects of multiple sensory deficits are not known.ObjectiveTo investigate longitudinal associations of the type, severity, and number of sensory impairments with physical function trajectories and mortality in older adults.Design, Setting, and ParticipantsThis retrospective analysis of a longitudinal cohort study, the Health, Aging, and Body Composition (Health ABC) study, incorporated data from April 1997 to July 2013, featuring a 16-year follow-up with annual examinations and questionnaires. The cohort comprised 3075 men and women, aged 70 to 79 years at baseline, residing in Memphis, Tennessee, and Pittsburgh, Pennsylvania. All participants with complete sensory testing and covariate data at analytical baseline (year 5, 2002) were included. The data were analyzed September 1, 2022.ExposuresVisual, olfactory, auditory, and touch sensory functions were assessed between 2000 and 2002.Main OutcomesThe main outcomes included physical functioning trajectories and mortality risk. Physical function was assessed longitudinally using the Health ABC physical performance battery (HABCPPB).ResultsA total of 1825 individuals (mean [SD] age, 77.4 [3.2] years; 957 [52%] female) were included in this study. Multivariable analysis of HABCPPB decline indicated that having 1 sensory impairment (β estimate, −0.01 [95% CI, −0.02 to −0.001]); 2 sensory impairments (β estimate, −0.01 [95% CI, −0.02 to −0.01]); 3 sensory impairments (β estimate, −0.03 [95% CI, −0.04 to −0.02]); or 4 sensory impairments (β estimate, −0.04 [95% CI, −0.05,−0.03]) was significantly associated with a steeper HABCPPB score decline in a dose-dependent manner. Adjusted Cox proportional hazards models indicated that having 1 sensory impairment (hazard ratio [HR], 1.35 [95% CI, 1.01-1.81]), 2 sensory impairments (HR, 1.58 [95% CI, 1.19-2.11]), 3 sensory impairments (HR, 1.79 [95% CI, 1.33-2.42]), or 4 sensory impairments (HR, 1.97 [95% CI, 1.39-2.79]) was significantly associated with increased mortality risk in a similarly dose-dependent manner.ConclusionIn this retrospective cohort study, the degree and number of multiple sensory impairments were associated with worse physical functioning and increased mortality risk. These findings represent an opportunity for further investigation into the value of screening, prevention, and treatment of sensory impairments to reduce morbidity and mortality in older adults.

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Inflammatory signatures in older persons with physical frailty and sarcopenia: The frailty “cytokinome” at its core

Cited by 85 publications

References 60 publications

Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature

Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature

The “develOpment of metabolic and functional markers of Dementia IN Older people” (ODINO) Study: Rationale, Design and Methods

Physical Function Trajectories and Mortality in Older Adults With Multisensory Impairment

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