Is metformin a geroprotector? A peek into the current clinical and experimental data

Zajda, Agnieszka; Huttunen, Kristiina M.; Sikora, Joanna; Podsiedlik, Maria; Markowicz-Piasecka, Magdalena

doi:10.1016/j.mad.2020.111350

Cited by 13 publications

(10 citation statements)

References 240 publications

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“…Besides, from the point of view of pharmacological intervention, many anti-aging drugs have been developed such as caloric restriction mimetics (resveratrol, rapamycin, metformin), senolytics, and synthetic sirtuin activators, which are promising to alleviate or delay age-related conditions. [38][39][40][41][42] With a more comprehensive understanding of aging hallmarks, more aging interventions are expected to flourish. Likewise, advances in biomedical research may bring us the possibility of anti-aging and delaying the onset of diseases in the future.…”

Section: Discussionmentioning

confidence: 99%

“…As the implementation of multi‐domain interventions in preventing cognitive decline and frailty has been suggested to be effective, 8,9,37 it is meaningful to extend such interventions to CVD, cancer, and even aging itself. Besides, from the point of view of pharmacological intervention, many anti‐aging drugs have been developed such as caloric restriction mimetics (resveratrol, rapamycin, metformin), senolytics, and synthetic sirtuin activators, which are promising to alleviate or delay age‐related conditions 38–42 . With a more comprehensive understanding of aging hallmarks, more aging interventions are expected to flourish.…”

Section: Discussionmentioning

confidence: 99%

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Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality

Li,

Cao,

Zhang

et al. 2023

J American Geriatrics Society

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BackgroundWith two well‐validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes.MethodsData were from 405,944 adults (40–69 years) from UK Biobank (UKB) and 9972 adults (20–84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0–5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all‐cause mortality in UKB; CVD mortality, cancer mortality, and all‐cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed.ResultsThe unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: β = 0.741; NHANES: β = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all‐cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure—BioAgeAccel.ConclusionsAccelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality

Li,

Cao,

Zhang

et al. 2023

J American Geriatrics Society

View full text Add to dashboard Cite

show abstract

“…As the implementation of multi-domain interventions in preventing cognitive decline and frailty has been suggested to be effective [9][10][11] , it is meaningful to extend such interventions to CVD, cancer, and even aging itself. Besides, from the point of view of pharmacological intervention, many anti-aging drugs have been developed such as caloric restriction mimetics (resveratrol, rapamycin, metformin), senolytics, and synthetic sirtuin activators, which are promising to alleviate or delay age-related conditions [36][37][38][39][40] . With a more comprehensive understanding of aging hallmarks, more aging interventions are expected to flourish.…”

Section: Discussionmentioning

confidence: 99%

Accelerated Aging Mediates the Associations of Unhealthy Lifestyles with Cardiovascular Disease, Cancer, and Mortality: Two Large Prospective Cohort Studies

Cao

Zhang

et al. 2022

Preprint

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With a well-validated aging measure – Phenotypic Age Acceleration (PhenoAgeAccel), this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9,972 adults (20-84 years) from US National Health and Nutrition Examination Surveys (NHANES). The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident cardiovascular disease, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (P values <0.001) in UKB, respectively. The mediation proportion of PhenoAgeAccel in associations of lifestyles with cancer mortality, and all-cause mortality were 25.7%, and 35.2% (P values <0.05) in NHANES, respectively. This study demonstrated that accelerated aging partially mediated the associations of lifestyles with adverse health outcomes in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late-life beyond lifestyle interventions.

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“…Studies have shown that neuroinflammation is involved in the pathogenesis of neurodegenerative diseases. Abnormal activation of microglia cells can lead to immune dysfunction and inflammation, in which microglia cells release inflammatory mediators and damage normal surrounding nerve tissue, gradually leading to degeneration and death of neurons ( Zajda et al, 2020 ). Due to the continuous abnormal immunity of microglia, chronic neuroinflammation leads to the destruction of neurons and synaptic structures, resulting in the development of neurodegenerative diseases such as AD, PD, and HD.…”

Section: Mechanisms and Signaling Pathways Of Metforminmentioning

confidence: 99%

Exploring the Pharmacological Potential of Metformin for Neurodegenerative Diseases

Gao

Liu

et al. 2022

Front. Aging Neurosci.

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Metformin, one of the first-line of hypoglycemic drugs, has cardioprotective, anti-inflammatory and anticancer activities, in addition to its proven hypoglycemic effects. Furthermore, the preventive and therapeutic potential of metformin for neurodegenerative diseases has become a topic of concern. Increasing research suggests that metformin can prevent the progression of neurodegenerative diseases. In recent years, many studies have investigated the neuroprotective effect of metformin in the treatment of neurodegenerative diseases. It has been revealed that metformin can play a neuroprotective role by regulating energy metabolism, oxidative stress, inflammatory response and protein deposition of cells, and avoiding neuronal dysfunction and neuronal death. On the contrary, some have hypothesized that metformin has a two-sided effect which may accelerate the progression of neurodegenerative diseases. In this review, the results of animal experiments and clinical studies are reviewed to discuss the application prospects of metformin in neurodegenerative diseases.

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Is metformin a geroprotector? A peek into the current clinical and experimental data

Cited by 13 publications

References 240 publications

Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality

Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality

Accelerated Aging Mediates the Associations of Unhealthy Lifestyles with Cardiovascular Disease, Cancer, and Mortality: Two Large Prospective Cohort Studies

Exploring the Pharmacological Potential of Metformin for Neurodegenerative Diseases

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