Cellular senescence and frailty: a comprehensive insight into the causal links

Marcozzi, Serena; Bigossi, Giorgia; Giuliani, Maria Elisa; Giacconi, Robertina; Piacenza, Francesco; Cardelli, Maurizio; Brunetti, Dario; Segala, Agnese; Valerio, Alessandra; Nisoli, Enzo; Lattanzio, Fabrizia; Provinciali, Mauro; Malavolta, Marco

doi:10.1007/s11357-023-00960-w

Cited by 4 publications

(2 citation statements)

References 192 publications

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“…Nonetheless, the age‐related impairment of the immune system concurrent with exponential growth in the senescence burden provides a strong rationale for senescence being a key player in the development of increased vulnerability in frail older individuals. 38 To the best of our knowledge, this is the first study demonstrating that systemic GDF‐15 is associated with frailty evaluated using the Clinical Frailty Scale. Whether this association is mediated by underlying physical frailty, cognitive frailty, or impairments across multiple physiological systems causing frailty is yet to be investigated.…”

Section: Discussionmentioning

confidence: 88%

GDF‐15 is associated with sarcopenia and frailty in acutely admitted older medical patients

Kamper,

Nygaard,

Praeger‐Jahnsen

et al. 2024

J cachexia sarcopenia muscle

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BackgroundGrowth differentiation factor‐15 (GDF‐15) has been associated with senescence, lower muscle strength, and physical performance in healthy older people. Still, it is not clear whether GDF‐15 can be utilized as a biomarker of sarcopenia and frailty in the early stages of hospitalization. We investigated the association of plasma GDF‐15 with sarcopenia and frailty in older, acutely admitted medical patients.MethodsThe present study is based on secondary analyses of cross‐sectional data from the Copenhagen PROTECT study, a prospective cohort study including 1071 patients ≥65 years of age admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg, Denmark. Muscle strength was assessed using handgrip strength, and lean mass was assessed using direct segmental multifrequency bioelectrical impedance analyses and used to clarify the potential presence of sarcopenia defined according to guidelines from the European Working Group on Sarcopenia in Older People. Frailty was evaluated using the Clinical Frailty Scale. Plasma GDF‐15 was measured using electrochemiluminescence assays from Meso Scale Discovery (MSD, Rockville, MD, USA).ResultsWe included 1036 patients with completed blood samples (mean age 78.9 ± 7.8 years, 53% female). The median concentration of GDF‐15 was 2669.3 pg/mL. Systemic GDF‐15 was significantly higher in patients with either sarcopenia (P < 0.01) or frailty (P < 0.001) compared with patients without the conditions. Optimum cut‐off points of GDF‐15 relating to sarcopenia and frailty were 1541 and 2166 pg/mL, respectively.ConclusionsSystemic GDF‐15 was higher in acutely admitted older medical patients with sarcopenia and frailty compared with patients without. The present study defined the optimum cut‐off for GDF‐15, related to the presence of sarcopenia and frailty, respectively. When elevated above the derived cutoffs, GDF‐15 was strongly associated with frailty and sarcopenia in both crude and fully adjusted models.

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Section: Discussionmentioning

confidence: 88%

GDF‐15 is associated with sarcopenia and frailty in acutely admitted older medical patients

Kamper,

Nygaard,

Praeger‐Jahnsen

et al. 2024

J cachexia sarcopenia muscle

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“…As the immune system becomes less effective with age, the accumulation of senescent cells can affect an individual’s ability to resist age-related conditions [ 19 , 23 ]. Therefore, cellular senescence has been linked to multiple age-related conditions, such as frailty, cardiovascular disease, and cognitive impairment [ 24 , 25 , 26 ]. Previous studies have used mouse models to study senescent cells [ 16 , 27 ].…”

Section: Cellular Senescence and Accelerated Aging In Cancer Survivorsmentioning

confidence: 99%

Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions

Wang,

El Jurdi,

Thyagarajan

et al. 2024

IJMS

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The population of cancer survivors has markedly increased due to the rapid improvements in cancer treatment. However, cancer survivors experience accelerated aging, which leads to chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after cancer diagnosis and treatment. Cellular senescence, a hallmark of aging, is one of the mechanisms that contribute to accelerated aging in cancer survivors. Several aging measures, including measures based on clinical markers and biomarkers, have been proposed to estimate the aging process, and some of them have shown associations with mortality and frailty in cancer survivors. Several anti-aging interventions, including lifestyle changes and anti-aging drugs, have been proposed. Future research, particularly in large-scale studies, is needed to determine the efficiency of these aging measures and anti-aging interventions before considering their application in clinics. This review focuses on the mechanisms of cellular senescence and accelerated aging in cancer survivors, assessment of the aging process using clinical markers and biomarkers, and the high prevalence of frailty in that population, as well as possible opportunities for anti-aging interventions. A deeper understanding of aging measures and anti-aging interventions in cancer survivors will contribute to the development of effective strategies to mitigate accelerated aging in cancer survivors and improve their quality of life.

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