Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study

Zhang, Hui; Meng, Hao; Hu, Zixin; Li, Yi; Jiang, Xiaoyan; Wang, Jiucun; Li, Jin; Liu, Zuyun; Sun, Xuying

doi:10.1186/s12979-021-00257-6

Cited by 24 publications

(16 citation statements)

References 40 publications

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“…In addition to the healthspan parameters focused on in this review, there are further health assessments that can be useful in intervention studies in aging mice. These include blood chemistry analysis, which provides information on glucose homeostasis, lipid metabolism, liver and kidney function, and inflammatory markers ( O’Connell et al, 2015 ; Palliyaguru et al, 2021a ; Zhang et al, 2022 ). Live animal imaging techniques, such as magnetic resonance imaging (MRI) ( Chen et al, 2011 ) and positron emission tomography (PET) ( Borrás et al, 2011 ; Hulsmans et al, 2018 ), can allow for the non-invasive visualization of organs and tissue and can therefore provide insights into structural and functional changes occurring with an intervention.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review

et al. 2023

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With an increasing aging population, the burden of age-related diseases magnifies. To alleviate this burden, geroprotection has been an area of intense research focus with the development of pharmacological interventions that target lifespan and/or healthspan. However, there are often sex differences, with compounds mostly tested in male animals. Given the importance of considering both sexes in preclinical research, this neglects potential benefits for the female population, as interventions tested in both sexes often show clear sexual dimorphisms in their biological responses. To further understand the prevalence of sex differences in pharmacological geroprotective intervention studies, we performed a systematic review of the literature according to the PRISMA guidelines. Seventy-two studies met our inclusion criteria and were classified into one of five subclasses: FDA-repurposed drugs, novel small molecules, probiotics, traditional Chinese medicine, and antioxidants, vitamins, or other dietary supplements. Interventions were analyzed for their effects on median and maximal lifespan and healthspan markers, including frailty, muscle function and coordination, cognitive function and learning, metabolism, and cancer. With our systematic review, we found that twenty-two out of sixty-four compounds tested were able to prolong both lifespan and healthspan measures. Focusing on the use of female and male mice, and on comparing their outcomes, we found that 40% of studies only used male mice or did not clarify the sex. Notably, of the 36% of pharmacologic interventions that did use both male and female mice, 73% of these studies showed sex-specific outcomes on healthspan and/or lifespan. These data highlight the importance of studying both sexes in the search for geroprotectors, as the biology of aging is not the same in male and female mice.Systematic Review Registration: [website], identifier [registration number].

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Section: Discussionmentioning

confidence: 99%

Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review

et al. 2023

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“…To date, only one other study has investigated the relationship between SII and frailty. Zhang et al [21] analyzed data from 1,822 older adults in the Rugao Longitudinal Aging Study, revealing that those with higher baseline SII levels (fourth quartile) faced over a twofold increase in the risk of developing frailty compared to those in the lowest SII quartile ( rst quartile). That study employed Fried's frailty phenotype [32] to categorize the frailty status of participants.…”

Section: Discussionmentioning

confidence: 99%

“…[10] Subsequent research has expanded its applicability beyond cancer to include patients undergoing surgery, individuals with intracerebral hemorrhage, and those with acute coronary syndrome. [11][12][13][14][15][16][17][18] Numerous studies have demonstrated the integral role of in ammation in the pathogenesis of frailty, highlighting signi cant associations between frailty and elevated levels of in ammatory markers such as C-reactive protein (CRP), [19] interleukin-6 (IL-6), [20] neutrophil-lymphocyte ratio (NLR), [21] and white cell count. [22] SII, calculated based on peripheral lymphocyte, neutrophil, and platelet counts, is postulated to offer a more comprehensive representation of both local immune response and systemic in ammation.…”

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confidence: 99%

Association of systemic immune-inflammation index with the risk of incident pre-frailty or frailty: the Chinese Longitudinal Healthy Longevity Survey

Li,

Gao,

et al. 2024

Preprint

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Background: Inflammation is a significant factor in the pathogenesis of frailty. While previous research has indicated that the systemic immune-inflammation index (SII) serves as a reliable marker for inflammation, the relationship between SII and newly developed frailty remains understudied. This study aims to explore the relationship between SII and incident pre-frailty and frailty among community-dwelling older adults. Methods: Data were drawn from participants in the 2008 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A 38-item frailty index (FI) was employed to assess frailty status and to classify participants into one of three categories: “robust” (FI ≤ 0.1), “pre-frail” (0.1 < FI ≤ 0.21), or “frail” (FI > 0.21). The SII was determined using the formula: SII = (white blood cell – lymphocyte) × (platelet count) / lymphocyte. A Cox regression model was utilized to evaluate the relationship between SII and the onset of pre-frailty and frailty. Results: The analysis included 676 participants classified as robust, with a median age of 80.0 years (interquartile range, 67.0, 91.0). Over a 3-year follow-up period, 159 participants progressed to a state of pre-frailty or frailty. The incidence of pre-frailty or frailty was 17.8%, 25.3%, and 27.6% across SII tertile groups, respectively (p < 0.05). Among participants initially categorized as robust in 2008, those in the highest SII tertile had a greater risk of developing pre-frailty or frailty compared to those in the lowest tertile (HR = 2.03; 95% CI: 1.12–3.70). Sensitivity analysis using the Fine-Gray model, accounting for death as a competing risk, also indicated an elevated risk for those in the highest SII tertile (HR = 1.53; 95% CI: 1.18–1.98). Conclusion: Among community-dwelling older adults, higher SII levels were associated with an increased risk of incident pre-frailty or frailty.

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“…A recent 2-yr longitudinal study assessed the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation index (SII), as indicators of immunesenescence, in 1,822 older adults for their association with incident frailty, using the physical frailty phenotype. Both log NLR and log SII were positively associated with incident frailty; the association remained when adjusted for multimorbidities ( 255 ). In contrast, a 5-yr longitudinal study in 657 >85-yr-old subjects found no association of T-cell senescence with loss of muscle function or prevalent or incident sarcopenia ( 256 ).…”

Section: The Physiological Phenotype Of Frailtymentioning

confidence: 99%

Multisystem physiological perspective of human frailty and its modulation by physical activity

Taylor

Greenhaff

Bartlett

et al. 2023

Physiological Reviews

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"Frailty" is a term used to refer to a state characterised by enhanced vulnerability to, and impaired recovery from, stressors, when compared to a non-frail state, which is increasingly viewed as a loss of resilience. With increasing life expectancy and the associated rise in years spent with physical frailty, there is a need to understand the clinical and physiological features of frailty and the factors driving it. We describe the clinical definitions of age-related frailty and their limitations in allowing us to understand the pathogenesis of this prevalent condition. Given age-related frailty manifests in the form of functional declines such as poor balance, falls and immobility, as an alternative we view frailty from a physiological viewpoint and describe what is known of the organ-based components of frailty, including adiposity, the brain, and neuromuscular, skeletal muscle, immune and cardiovascular systems, as individual systems and as components in multisystem dysregulation. By doing so we aim to highlight current understanding of the physiological phenotype of frailty and reveal key knowledge gaps and potential mechanistic drivers of the trajectory to frailty. We also review the studies in humans that have intervened with exercise to reduce frailty. We conclude that more longitudinal and interventional clinical studies are required in older adults. Such observational studies should interrogate the progression from a non-frail to a frail state, assessing individual elements of frailty to produce a deep physiological phenotype of the syndrome. The findings will identify mechanistic drivers of frailty and allow targetted interventions to diminish frailty progression.

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Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study

Cited by 24 publications

References 40 publications

Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review

Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review

Association of systemic immune-inflammation index with the risk of incident pre-frailty or frailty: the Chinese Longitudinal Healthy Longevity Survey

Multisystem physiological perspective of human frailty and its modulation by physical activity

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