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Cited by 140Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in Medicine

The costs and benefits of senotherapeutics for human health

Open access
Raffaele, Marco, Vinciguerra, Manlio·2022·The Lancet Healthy Longevity
DOI 10.1016/s2666-7568(21)00300-7
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Abstract

Cellular senescence is a major contributor to age-related diseases in humans; however, it also has a beneficial role in physiological and pathological processes, including wound healing, host immunity, and tumour suppression. Reducing the burden of cell senescence in animal models of cardiometabolic disorders, inflammatory conditions, neurodegenerative diseases, and cancer using pharmaceutical approaches that selectively target senescent cells (ie, senolytics) or that suppress senescence-associated secretory phenotype (ie, senomorphics) holds great promise for the management of chronic age-associated conditions. Although studies have provided evidence that senolytics or senomorphics are effective at decreasing the number of senescent cells in humans, the short-term and long-term side-effects of these therapies are largely unknown. In this Review, we systematically discuss the senolytics and senomorphics that have been investigated in clinical trials or have been used off-label, presenting their various adverse effects. Despite the potential of senotherapeutics to transform anti-ageing medicine, a cautionary approach regarding unwanted dose-dependent side-effects should be adopted.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that senotherapeutics (senolytics and senomorphics) show promise for age-related diseases in preclinical models and some early human trials, but human efficacy and safety data remain sparse. It catalogues organ-specific benefits and adverse effects, cautioning that dose-dependent side-effects and unstandardised protocols limit clinical translation.

Key findings

  • Early human senolytic trials show target engagement: in seven patients with diabetic kidney disease, once-daily oral dasatinib (100 mg) plus quercetin (1000 mg) for 3 days reduced senescent-cell burden in adipose tissue within 11 days; another pilot reduced p16INK4a-positive cells by 38% and p21CIP1-positive cells by 30% in skin and adipose tissue.
  • In a phase 1 study of UBX1325 in 12 patients with diabetic macular oedema or age-related macular degeneration, there were no dose-limiting toxicities and two non-serious adverse events unrelated to the drug; six high-dose patients gained best corrected visual acuity at 2 weeks, six of 12 had decreased central subfield thickness, and three of four patients with wet age-related macular degeneration improved.
  • In 14 patients with idiopathic pulmonary fibrosis, intermittent dasatinib (100 mg/day) plus quercetin (1250 mg/day) for 3 days per week over 3 weeks was tolerable and improved 6-min walk distance and 4-m gait speed, but pulmonary function, circulating senescence/profibrotic markers, frailty index scores, and reported health were unchanged.
  • Adverse or divergent effects include ABT263 reducing trabecular bone volume fraction by 60.1% in female and 45.6% in male aged mice and impairing osteoblast mineralised matrix production by 88% in females and 83% in males; Bcl-xL inhibitors induced thrombocytopenia/thrombocytopathy; and UBX0101 failed a phase 2 trial in knee osteoarthritis.

Methods

  • Design: a Review, described by the authors as systematically discussing senolytics and senomorphics investigated in clinical trials or used off-label, broken down by physiological function and organ system in patients and murine models.
  • Data: PubMed searched June 23–Aug 31, 2021, using MeSH and free-text terms including “senolytics” OR “cellular senescence” and specific combinations; ClinicalTrials.gov searched Aug 25–Nov 8, 2021, using senolytic names AND “senescence” OR “senolytic” OR “aging”; no language, date, or publication-status restriction.
  • Analysis: narrative synthesis of preclinical and clinical evidence, including a table of clinical trials; no meta-analysis or formal quantitative pooling is described.

Limitations

  • Stated: short-term and long-term side-effects of senotherapeutics are largely unknown; there is a paucity of efficacy and safety data from clinical trials; standardised guidelines for timing, dose, and route of administration are absent; and peripheral tissues are incompletely functionally characterised after systemic administration.
  • Stated: findings are discordant across models—for example, dasatinib plus quercetin has not always been efficacious in metabolic disease, and ABT263 has shown both beneficial and detrimental bone effects—so long-term monitoring and randomised controlled trials are needed.
  • Evident from the text: many conclusions rely on murine models, while human evidence often comes from small, open-label, single-arm pilot studies; the literature search was limited to PubMed and ClinicalTrials.gov over defined 2021 windows, and no formal risk-of-bias assessment or meta-analysis is described.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/s2666-7568(21)00300-7

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 121 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    Several pilot studies in humans testing senolytics in recipients of haematopoietic stem-cell transplantation, patients with age-related osteoporosis, and patients with osteoarthritis are currently recruiting or ongoing.

    “Nevertheless, several pilot studies in humans testing the potential beneficial effects of senolytics in recipients of haematopoietic stem-cell transplantation, patients with age-related osteoporosis, and patients with osteoarthritis are currently recruiting or ongoing (table).”
    Quote in the paperNot a substantial claim
  • Findingnone given

    To date, only a few studies have investigated use of senotherapeutics in the kidney.

    “However, to date, only a few studies have investigated use of these drugs.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Elimination of senescent cells seemed to be largely beneficial.

    “The body of evidence showing that elimination of senescent cells seemed to be largely beneficial 6,7 led to huge research efforts to identify novel agents that eliminate senescent cells in humans.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Baker, 2016, Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan, Nature source

      Not checked in the free run.

    • cites [7] Kirkland, 2017, The clinical potential of senolytic drugs, J Am Geriatr Soc source

      Not checked in the free run.

  • Interpretationreasoning

    The full potential of senotherapeutics has been hampered in clinical applications.

    “Therefore, the full potential of senotherapeutics has been hampered in clinical applications.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Studies have provided evidence that senolytics or senomorphics are effective at decreasing the number of senescent cells in humans.

    “Although studies have provided evidence that senolytics or senomorphics are effective at decreasing the number of senescent cells in humans, the short-term and long-term side-effects of these therapies are largely unknown.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Hickson, 2020, Corrigendum to ‘Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease’ EBioMedicine 47 (2019) 446–456, EBioMedicine source

      Not checked in the free run.

  • May combine two claims. 61
  • Classified as probably not a substantial claim. 8

  • May combine two claims.

    Interpretationnone given

    Repurposing existing drugs and using new senotherapeutics are associated with various side-effects, incomplete functional characterisation of peripheral tissues at systemic administration, an absence of standardised guidelines for timing, dose, and route of administration, and a paucity of efficacy and safety data from clinical trials.

    “However, the repurposing of existing drugs and the use of new senotherapeutics are associated with various side-effects; incomplete functional characterisation of peripheral tissues at systemic administration; an absence of standardised guidelines for timing, dose, and route of administration; and a paucity of efficacy and safety data from clinical trials.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Senolytics decrease the number of naturally occurring senescent human cells in vitro, and improve physical function and increase the lifespan of aged mice.

    “Senolytics decrease the number of naturally occurring senescent human cells in vitro, and improve physical function and increase the lifespan of aged mice.12,13”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] Xu, 2018, Senolytics improve physical function and increase lifespan in old age, Nat Med source

      Not checked in the free run.

    • cites [13] Yousefzadeh, 2018, Fisetin is a senotherapeutic that extends health and lifespan, EBioMedicine source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The senescence-associated secretory phenotype (SASP) is a hallmark of senescent cells that mediates their pathophysiological effects, characterised by increased secretion of cytokines, chemokines, proteases, and growth factors.

    “In this respect, the senescence-associated secretory phenotype (SASP), a hallmark of senescent cells that mediates their pathophysiological effects, is characterised by the increased secretion of some bioactive molecules, including cytokines, chemokines, proteases, and growth factors.2”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Gorgoulis, 2019, Cellular senescence: defining a path forward, Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tissue ageing is caused by the accumulation of senescent cells, which alters physiological responses in the surrounding microenvironment in an autocrine and paracrine fashion through SASP.

    “Over the past decade, it has become clear that tissue ageing is caused by the accumulation of senescent cells, which alters the physiological responses in the surrounding microenvironment in an autocrine and paracrine fashion through SASP.2,3”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] Gorgoulis, 2019, Cellular senescence: defining a path forward, Cell source

      Not checked in the free run.

    • cites [3] Coryell, 2021, Mechanisms and therapeutic implications of cellular senescence in osteoarthritis, Nat Rev Rheumatol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Senescent adipocyte progenitors secrete activin A, a member of the transforming growth factor superfamily, and directly inhibit adipogenesis in non-senescent progenitors.

    “In 2015, researchers from the Mayo Clinic showed that senescent adipocyte progenitors secrete activin A, a member of the transforming growth factor superfamily, and directly inhibit adipogenesis in non-senescent progenitors.44”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Zaragosi, 2010, Activin a plays a critical role in proliferation and differentiation of human adipose progenitors, Diabetes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The incidence of cancer increases when people get older because of the increased burden of cell senescence in organs, partly due to an impaired immune system, which results in reduced clearance of senescent cells.

    “Nevertheless, the incidence of cancer increases when people get older because of the increased burden of cell senescence in organs, partly due to an impaired immune system, which results in a reduced clearance of senescent cells.4”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Campisi, 2013, Aging, cellular senescence, and cancer, Annu Rev Physiol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Intermittent administration of senolytics improves drug safety and reduces the risk of side-effects.

    “Consequently, drug safety is improved and the risk of side-effects is reduced.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Senescent cells accumulate in the heart with age and contribute to related pathologies in animal models.

    “It has been shown that senescent cells accumulate in the heart with age and contribute to related pathologies in animal models.27”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Anderson, 2019, Length-independent telomere damage drives post-mitotic cardiomyocyte senescence, EMBO J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Five days after a single dose of dasatinib (5 mg/kg) and quercetin (50 mg/kg), expression of senescent markers was reduced and exercise endurance was better than in vehicle-treated controls.

    “5 days after a single dose of dasatinib (5 mg/kg) and quercetin (50 mg/kg) by oral gavage, expression of senescent markers was reduced and exercise endurance was better than in vehicle-treated controls.28”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Zhu, 2015, The Achilles' heel of senescent cells: from transcriptome to senolytic drugs, Aging Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ABT263 had no significant effect on cardiac function, left ventricle mass, or ventricle wall rigidity.

    “However, ABT263 had no significant effect on cardiac function, left ventricle mass, or ventricle wall rigidity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Anderson, 2019, Length-independent telomere damage drives post-mitotic cardiomyocyte senescence, EMBO J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Six of 12 patients had a decrease in central subfield thickness, and three of four patients with wet age-related macular degeneration saw an improvement in disease-relevant pathology and a reduction in subretinal or intraretinal fluid.

    “Six of 12 patients had a decrease in central subfield thickness, and three of four patients with wet age-related macular degeneration saw an improvement in disease-relevant pathology and a reduction in subretinal or intraretinal fluid.47”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In aged mice, resting satellite cells lose the ability to repress P16ink4a (Cdkn2a), switching from the reversible quiescent state to an irreversible pre-senescence state; when injured, these cells fail to activate and expand, entering full senescence.

    “In aged mice, resting satellite cells lose the ability to repress P16ink4a (Cdkn2a), switching from the reversible quiescent state to an irreversible pre-senescence state.When injured, these cells fail to activate and expand, entering full senescence.51”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Sousa-Victor, 2014, Geriatric muscle stem cells switch reversible quiescence into senescence, Nature source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the Apoe-knockout mouse model of atherogenesis, treatment with dasatinib and quercetin decreased the burden of senescence and plaque calcification, even though no change in plaque size was observed.

    “Treatment with dasatinib and quercetin decreased the burden of senescence and plaque calcification, even though no change in plaque size was observed.25”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Roos, 2016, Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice, Aging Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Clearance of senescent cells reduced the number of macrophages in visceral adipose tissue and prevented the migration of monocytes.

    “Additionally, clearance of senescent cells reduced the number of macrophages in visceral adipose tissue and prevented the migration of monocytes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Palmer, 2019, Targeting senescent cells alleviates obesity-induced metabolic dysfunction, Aging Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Senescent cells accumulate with age in the dermis and epidermis, which can be accelerated by various harmful factors, such as DNA-damaging agents and mitochondrial dysfunction.

    “Senescent cells accumulate with age in the dermis and epidermis, which can be accelerated by various harmful factors, such as DNA-damaging agents (eg, x-rays, ultraviolet radiation, and cigarette smoke) and mitochondrial dysfunction.56”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Watanabe, 2017, Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases, Cancer Sci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    UBX1325 showed a favourable acute safety profile supporting further clinical development; there were no dose-limiting toxicities and two non-serious adverse events unrelated to the drug.

    “UBX1325 showed a favourable acute safety profile supporting further clinical development; there were no doselimiting toxicities and two non-serious adverse events unrelated to the drug.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ABT263 rescued the functional decrease in ejection fraction occurring after myocardial infarction in aged mice, improved left ventricular function, increased myocardial vascularisation, decreased scar size, and attenuated the inflammatory response in a young mouse model of ischaemia-reperfusion.

    “Subsequently, it was shown that ABT263 was able to rescue the functional decrease in ejection fraction occurring after myocardial infarction in aged mice, to improve left ventricular function, to increase myocardial vascularisation, to decrease scar size, and to attenuate the inflammatory response in a young mouse model of ischaemia-reperfusion.23,24”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [23] Walaszczyk, 2019, Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction, Aging Cell source

      Not checked in the free run.

    • cites [24] Dookun, 2020, Clearance of senescent cells during cardiac ischemia-reperfusion injury improves recovery, Aging Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Clearance of senescent cells in aged mice and in mice with atherosclerosis using genetic and pharmacological approaches improves vascular and myocardial function and attenuates age-dependent remodelling.

    “Clearance of senescent cells in aged mice and in mice with atherosclerosis using genetic and pharmacological approaches improves vascular and myocardial function and attenuates age-dependent remodelling.25,27”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Roos, 2016, Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice, Aging Cell source

      Not checked in the free run.

    • cites [27] Anderson, 2019, Length-independent telomere damage drives post-mitotic cardiomyocyte senescence, EMBO J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Skeletal muscle mass and function decline with ageing, culminating in sarcopenia, and are linked to an increased burden of senescent cells with involvement of the immune system.

    “Skeletal muscle mass and function decline with ageing, culminating in sarcopenia, and are linked to an increased burden of senescent cells with involvement of the immune system.52,53”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [52] Vinciguerra, 2010, Regulation of muscle atrophy in aging and disease, Adv Exp Med Biol source

      Not checked in the free run.

    • cites [53] Vinciguerra, 2019, Sarcopenia and Parkinson's Disease

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a prospective cohort of 227 individuals with severe obesity, senescence-associated β-galactosidase activity was seven times higher in subcutaneous tissue than in omental adipose tissue and was correlated with altered glycaemic status; however, this activity was not associated with body-mass index or chronological age.

    “Senescence-associated β-galactosidase activity was seven times higher in subcutaneous tissue than in omental adipose tissue and was correlated with altered glycaemic status; however, this activity was not associated with body-mass index or chronological age.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Rouault, 2021, Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity, Diabetologia source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice with Ldlr deficiency fed a high-fat diet, treatment with ABT263 led to inhibited atherogenesis and reduced number and average size of plaques.

    “A study in mice aged 10 weeks with Ldlr deficiency, fed a high-fat diet (a reliable model of atherosclerosis in mice), and treated once daily with 100 mg/kg ABT263 for 5 days followed by 14 days off treatment on a repeating cycle for 88 days, showed that elimination of senescent cells led to inhibited atherogenesis and reduced the number and average size of plaques.26”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Childs, 2016, Senescent intimal foam cells are deleterious at all stages of atherosclerosis, Science source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A wealth of literature shows that exercise or physical activity might be the most cost-effective senolytic therapy, although there is large heterogeneity among published studies.

    “However, a wealth of literature shows that exercise or physical activity might be the most costeffective senolytic therapy, although there is large heterogeneity among published studies.54”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Chen, 2021, Is exercise a senolytic medicine? A systematic review, Aging Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Use of dasatinib and quercetin has not always been efficacious in every mouse model of metabolic disease; its efficacy seems to be controversial.

    “Given that use of dasatinib and quercetin has not always been efficacious in every mouse model of metabolic disease, its efficacy seems to be controversial.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21] Ogrodnik, 2017, Cellular senescence drives age-dependent hepatic steatosis, Nat Commun source

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    • cites [22] Raffaele, 2021, Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin, Cell Commun Signal source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In aged mice, ruxolitinib lowered the number of senescent cells and circulating concentration of activin A, preserved fat mass, decreased lipotoxicity, and enhanced insulin sensitivity.

    “The researchers found that this treatment lowered the number of senescent cells and circulating concentration of activin A, preserved fat mass, decreased lipotoxicity, and enhanced insulin sensitivity.19”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Xu, 2015, Targeting senescent cells enhances adipogenesis and metabolic function in old age, eLife source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment with ABT263 in aged mice showed a significant reduction in heart hypertrophy and fibrosis, together with a compensatory regeneration in cardiomyocytes.

    “Treatment with ABT263 showed a significant reduction in heart hypertrophy and fibrosis, together with a compensatory regeneration in cardiomyocytes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Anderson, 2019, Length-independent telomere damage drives post-mitotic cardiomyocyte senescence, EMBO J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dasatinib and quercetin decreased the burden of senescent cells and reduced hepatic steatosis in one study, but failed to promote clearance of senescent cells and prevent progression of non-alcoholic fatty liver disease in lean mice and in mice with obesity induced by a high-fat diet.

    “Although this senolytic cocktail was shown to decrease the burden of senescent cells and reduce hepatic steatosis in one study, 21 it failed to promote clearance of senescent cells and prevent progression of non-alcoholic fatty liver disease in lean mice and in mice with obesity induced by a high-fat diet.22”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21] Ogrodnik, 2017, Cellular senescence drives age-dependent hepatic steatosis, Nat Commun source

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    • cites [22] Raffaele, 2021, Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin, Cell Commun Signal source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    After 12 weeks of leg irradiation, mice aged 4 months showed impaired capacity in a treadmill exercise and an increased expression of senescent markers in the leg muscles.

    “After 12 weeks of leg irradiation (10 Gy), mice aged 4 months showed impaired capacity in a treadmill exercise and an increased expression of senescent markers in the leg muscles.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Zhu, 2015, The Achilles' heel of senescent cells: from transcriptome to senolytic drugs, Aging Cell source

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  • May combine two claims.

    Interpretationreasoning

    Experimental findings in mice indicate that cellular senescence could be a potential causal factor in obesity-related inflammation and metabolic imbalance, and that senolytic agents could be a promising treatment for obesity-related metabolic dysfunction and its complications.

    “These experimental findings in mice indicate that cellular senescence could be a potential causal factor in obesity-related inflammation and in metabolic imbalance, and that senolytic agents could be a promising treatment for obesity-related metabolic dysfunction and its complications.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In mice, senescent cells have shown the capacity to limit fibrosis and to promote proper wound healing through their secretion of platelet-derived growth factor AA in SASP, and chronic induction of cellular senescence might contribute to stem-cell loss with age.

    “In mice, senescent cells have shown the capacity to limit fibrosis and to promote proper wound healing through their secretion of platelet-derived growth factor AA in SASP, 58 and chronic induction of cellular senescence might contribute to stem-cell loss with age.59”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [58] Demaria, 2014, An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA, Dev Cell source

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    • cites [59] Velarde, 2015, Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells, Proc Natl Acad Sci USA source

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  • May combine two claims.

    Interpretationreasoning

    Collectively, these findings show that senescence has a key role in brain ageing and in related diseases in mice, and that senolytics can improve brain performance.

    “Collectively, these findings show that senescence has a key role in brain ageing and in related diseases in mice, and that senolytics can improve brain performance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Senolytic drugs can eliminate p16-positive macrophages and senescent vascular cells, exerting a dual approach to reverse vascular remodelling.

    “Senolytic drugs can eliminate p16-positive macrophages 85 and senescent vascular cells, exerting a dual approach to reverse vascular remodelling.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] Kakkola, 2013, Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice, Cell Death Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a doubletransgenic mouse model with induced human p14ARF gene expression, senescent cells increased in the epidermis and hair follicles arrested in the telogen stage.

    “Another study, investigating the age-related increase of hair loss, used a doubletransgenic mouse model, in which human p14ARF gene expression was induced, leading to an increase of senescent cells in the epidermis and the growth arrest of hair follicles in the telogen stage.43”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Yosef, 2016, Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL, Nat Commun source

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    Premisecitation

    Clearance of senescent cells enhances brain function in healthy aged mice and in various murine models of neurodegenerative diseases, such as Parkinson's disease, neurodegeneration related to amyloid β, tau-dependent neurodegenerative diseases, and neuropsychiatric disorders.

    “Clearance of senescent cells has been shown to enhance brain function in healthy aged mice 71 and in various murine models of Review neurodegenerative diseases, such as Parkinson's disease, 72 neurodegeneration related to amyloid β, 40 tau-dependent neurodegenerative iseases, 39 and neuropsychiatric disorders.73”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [71] Ogrodnik, 2021, Whole-body senescent cell clearance alleviates age-related brain inflammation and cognitive impairment in mice, Aging Cell source

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    • cites [72] Chinta, 2018, Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to Parkinson's disease, Cell Rep source

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    • cites [73] Ogrodnik, 2019, Obesity-induced cellular senescence drives anxiety and impairs neurogenesis, Cell Metab source

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  • May combine two claims.

    Premisecitation

    Intraperitoneal administration of ABT737 resulted in clearance of senescent cells in the epidermis and hair follicles, increasing non-senescent bulge capacity for proliferation and repopulation.

    “Intraperitoneal administration of 75 mg/kg ABT737 on 2 or 4 consecutive days resulted in clearance of senescent cells in the epidermis and hair follicles, increasing non-senescent bulge capacity for proliferation and repopulation.43”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Yosef, 2016, Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL, Nat Commun source

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    Premisecitation

    In that study, pulmonary function, circulating concentrations of biochemical markers of senescence and profibrotic factors, frailty index scores, and reported health were unchanged.

    “By contrast, pulmonary function, circulating concentrations of biochemical markers of senescence and profibrotic factors, frailty index scores, and reported health were unchanged.86”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Justice, 2019, Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study, EBioMedicine source

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    Premisecitation

    This plant extract reduced the expression of various SASP components, ameliorating the negative paracrine crosstalk between these cells.

    “This plant extract reduced the expression of various SASP components, ameliorating the negative paracrine crosstalk between these cells.60”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Lämmermann, 2018, Blocking negative effects of senescence in human skin fibroblasts with a plant extract, NPJ Aging Mech Dis source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    IL-6 is a chemotactic and prosurvival factor for monocytes and neutrophils.

    “IL-6 is a chemotactic and prosurvival factor for monocytes and neutrophils.83”
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    • cites [83] Kaplanski, 2003, IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation, Trends Immunol source

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    Interpretationcitation

    This pilot study implies that senolytic drugs might not have clinically significant toxicity and, therefore, could be safe for use in humans.

    “This pilot study implies that senolytic drugs might not have clinically significant toxicity and, therefore, could be safe for use in humans.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Prolonged expression of transgenic p16INK4a in the epidermis of mice induced hyperplasia and dysplasia through a paracrine-mediated activation of the Wnt pathway, contributing to the development of premalignant skin lesions.

    “In 2020, Azazmeh and colleagues 42 showed that prolonged expression of transgenic p16INK4a in the epidermis of mice induced hyperplasia and dysplasia through a paracrine-mediated activation of the Wnt pathway, contributing to the development of premalignant skin lesions.”
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    • cites [42] Azazmeh, 2020, Chronic expression of p16INK4a in the epidermis induces Wnt-mediated hyperplasia and promotes tumor initiation, Nat Commun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Aged mice acutely infected with pathogens, including murine-β-coronavirus related to SARS-CoV-2, had increased senescence and 100% mortality.

    “A Science report showed that aged mice acutely infected with pathogens, including murine-β-coronavirus related to SARS-CoV-2, had increased senescence and 100% mortality.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Camell, 2021, Senolytics reduce coronavirus-related mortality in old mice, Science source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Targeting senescent cells with either fisetin (20 mg/kg per day) or dasatinib (5 mg/kg) plus quercetin (50 mg/kg) on days 3, 4, 11, and 12 after pathogen exposure significantly reduced mortality (by 50%), cellular senescence, and inflammation, and increased antiviral responses.

    “Targeting senescent cells with either fisetin (20 mg/kg per day) or dasatinib (5 mg/kg) plus quercetin (50 mg/kg) on days 3, 4, 11, and 12 after pathogen exposure significantly reduced mortality (by 50%), cellular senescence, and inflammation, and increased antiviral responses.15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Camell, 2021, Senolytics reduce coronavirus-related mortality in old mice, Science source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a retrospective study of 28 patients with glaucoma, senolytic exposure did not affect visual acuity or intraocular pressure, and did not have toxic effects.

    “Although a study in a mouse model showed that dasatinib prevented glaucoma-dependent loss of retinal functions and cellular structure, 41 a retrospective study assessing the effects of senolytic drugs on vision in 28 patients with glaucoma showed that senolytic exposure did not affect visual acuity or intraocular pressure, and did not have toxic effects.74”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [74] El-Nimri, 2020, Evaluating the neuroprotective impact of senolytic drugs on human vision, Sci Rep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a single-arm, open-label clinical trial in 12 patients with interstitial lung disease associated with systemic sclerosis, only three (25%) patients showed some clinical improvement, which correlated with a decrease in skin expression of SASP and other senescence-related gene sets.

    “Only three (25%) patients showed some clinical improvement, which correlated with a decrease in skin expression of SASP and other senescence-related gene sets.61”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Martyanov, 2019, Senescence signature in skin biopsies from systemic sclerosis patients treated with senolytic therapy: potential predictor of clinical response?, Arthritis Rheumatol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Senotherapy ameliorated phenotypes in all of these mouse models, attenuating tau phosphorylation and aggregation, reducing neuroinflammation and amyloid β plaque load, and improving cognitive deficits.

    “Senotherapy has been shown to ameliorate phenotypes in all of these mouse models, attenuating tau phosphorylation and aggregation, 39 reducing neuroinflammation and amyloid β plague load, and improving cognitive deficits.40”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Bussian, 2018, Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline, Nature source

      Not checked in the free run.

    • cites [40] Zhang, 2019, Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model, Nat Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In macrophages, p16 expression is associated with proliferation of and differentiation into the proinflammatory M1 macrophage, leading to increased IL-6 secretion.

    “In macrophages, p16 expression is associated with proliferation of and differentiation into the proinflammatory M1 macrophage, 84 leading to increased IL-6 secretion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Frescas, 2017, Murine mesenchymal cells that express elevated levels of the CDK inhibitor p16(Ink4a) in vivo are not necessarily senescent, Cell Cycle source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Use of dasatinib (5 mg/kg) and quercetin (50 mg/kg) by oral gavage once a week for 3 weeks improved pulmonary function and physical health, although lung fibrosis was visibly unaltered.

    “The use of dasatinib (5 mg/kg) and quercetin (50 mg/kg) by oral gavage once a week for 3 weeks improved pulmonary function and physical health, although lung fibrosis was visibly unaltered.37”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Schafer, 2017, Cellular senescence mediates fibrotic pulmonary disease, Nat Commun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intraperitoneal administration of ABT737 eliminated p16-positive cells, inactivated the Wnt pathway, and subsequently suppressed hyperplasia.

    “Intraperitoneal administration of the ABT263 analogue, ABT737 (75 mg/kg six times over 9 days after 6 months of Cdk2a induction), eliminated p16-positive cells, inactivated the Wnt pathway, and subsequently suppressed hyperplasia.42”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Azazmeh, 2020, Chronic expression of p16INK4a in the epidermis induces Wnt-mediated hyperplasia and promotes tumor initiation, Nat Commun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intraperitoneal administration of ABT263 reversed vascular remodelling and improved pulmonary haemodynamics in the end stage of shunt-induced pulmonary arterial hypertension in a rat model.

    “Van der Feen and colleagues 36 showed that intraperitoneal administration of ABT263 (10 mg/kg daily for 7 days) reversed vascular remodelling and improved pulmonary haemodynamics in the end stage of shuntinduced pulmonary arterial hypertension in a rat model.36”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] van der Feen, 2020, Cellular senescence impairs the reversibility of pulmonary arterial hypertension, Sci Transl Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FOXO4-DRI (5 mg/kg injected every 2 days for 6 days) triggers selective apoptosis in senescent cells induced by ageing and by chemotherapy, resulting in improvement in mouse health, including protection of renal structure and function.

    “The most important contribution came from Baar and colleagues, 17 who designed the interfering peptide, FOXO4-DRI (5 mg/kg injected every 2 days for 6 days), which was shown to trigger selective apoptosis in senescent cells induced by ageing and by chemotherapy, resulting in an improvement in mouse health, including protection of renal structure and function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Baar, 2017, Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging, Cell source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Haematopoiesis involves both haematopoietic and nonhaematopoietic cells.

    “It is well established that haematopoiesis, the generation of new blood cells that takes place in the bone marrow, involves both haematopoietic and nonhaematopoietic cells.94”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] Dorshkind, 1990, Regulation of hemopoiesis by bone marrow stromal cells and their products, Annu Rev Immunol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dasatinib, quercetin, and other senolytics were discovered using a mechanism-based approach.

    “Dasatinib, quercetin, and other senolytics were discovered using a mechanism-based approach.7,26,105”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7] Kirkland, 2017, The clinical potential of senolytic drugs, J Am Geriatr Soc source

      Not checked in the free run.

    • cites [26] Childs, 2016, Senescent intimal foam cells are deleterious at all stages of atherosclerosis, Science source

      Not checked in the free run.

    • cites [105] Pignolo, 2020, Reducing senescent cell burden in aging and disease, Trends Mol Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oral administration of ABT263 in sublethally irradiated mice and naturally aged mice resulted in mitigation of premature ageing of the haematopoietic system induced by total body irradiation and rejuvenation of aged haematopoietic stem cells.

    “In 2016, Chang and colleagues 30 showed that oral administration of ABT263 in sublethally irradiated mice and naturally aged mice resulted in a mitigation of premature ageing of the haematopoietic system induced by total body irradiation and a rejuvenation of aged haematopoietic stem cells.30”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Chang, 2016, Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice, Nat Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ABT263 treatment in aged female and male mice reduced trabecular bone volume fraction (by 60.1% in females and 45.6% in males) and the ability of osteoblasts derived from bone marrow stem cells to produce mineralised matrix (by 88% in females and 83% in males), despite decreasing the burden of senescent cells.

    “However, another study showed that, despite decreasing the burden of senescent cells, ABT263 treatment in aged female and male mice reduced both trabecular bone volume fraction (by 60•1% in females and by 45•6% in males) and the ability of osteoblasts derived from bone marrow stem cells to produce mineralised matrix (by 88% in females and by 83% in males).35”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Sharma, 2020, The senolytic drug navitoclax (ABT-263) causes trabecular bone loss and impaired osteoprogenitor function in aged mice, Front Cell Dev Biol source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Results of experiments based exclusively on transgenic mice might not fully characterise the spectra of senescent cells seen in vivo, suggesting that the use of senotherapeutics could be a valid alternative to explore the effect of eliminating senescent cells in the kidney.

    “The results of experiments based exclusively on transgenic mice might not fully characterise the spectra of senescent cells seen in vivo, suggesting that the use of senotherapeutics could be a valid alternative to explore Review the effect of eliminating senescent cells in the kidney.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ABT263 and other Bcl-xL-inhibitory BH3 mimetics induced thrombocytopenia and a transient thrombocytopathy, which could impair the haemostatic function of platelets.

    “However, several other studies indicated that ABT263 and other Bcl-xL-inhibitory BH3 mimetics induced thrombocytopenia and a transient thrombocytopathy, which could impair the haemostatic function of platelets.33,34”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] Schoenwaelder, 2011, Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets, Blood source

      Not checked in the free run.

    • cites [34] He, 2020, Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity, Nat Commun

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The open-label phase 1 pilot study did not report effects on metabolic and renal function and can be considered preliminary.

    “This study did not report effects on metabolic and renal function, and can be considered preliminary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Ageing and genotoxic stress induce cellular senescence of haematopoietic stem cells and osteoprogenitor cells, with subsequent decline in their functions in both mice and humans.

    “Ageing and genotoxic stress induce cellular senescence of these stem cells 96,97 and osteoprogenitor cells, 98,99 with subsequent decline in the functions of these cells in both mice and humans.100”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [96] Shao, 2014, Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner, Blood source

      Not checked in the free run.

    • cites [97] Le, 2010, Ionizing radiation-induced long-term expression of senescence markers in mice is independent of p53 and immune status, Aging Cell source

      Not checked in the free run.

    • cites [98] Li, 2017, FOXP1 controls mesenchymal stem cell commitment and senescence during skeletal aging, J Clin Invest source

      Not checked in the free run.

    • cites [99] Oh, 2014, Stem cell aging: mechanisms, regulators and therapeutic opportunities, Nat Med source

      Not checked in the free run.

    • cites [100] Lee, 2019, Causes and mechanisms of hematopoietic stem cell aging, Int J Mol Sci

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Bone ageing is a major risk factor for primary osteoporosis, an age-related disease characterised by altered bone metabolism that suppresses bone formation and promotes bone resorption, impairing bone homoeostasis.

    “Bone ageing is major risk factor for primary osteoporosis, an age-related disease characterised by altered bone metabolism that suppresses bone formation and promotes bone resorption, 91 impairing bone homoeostasis.92”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [91] Rachner, 2011, Osteoporosis: now and the future, Lancet source

      Not checked in the free run.

    • cites [92] Infante, 2018, Osteogenesis and aging: lessons from mesenchymal stem cells, Stem Cell Res Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Targeting senescent cells in aged mice (20-24 months) with established bone loss by dasatinib (5 mg/kg) plus quercetin (50 mg/kg) once monthly for 4 months, or by ABT263 (41 μmol/kg) daily for 5 days, lowered bone resorption, with maintained trabecular bone formation and enhanced cortical bone formation.

    “Some studies have shown that targeting senescent cells in aged mice (aged 20-24 months) with established bone loss by use of dasatinib (5 mg/kg) plus quercetin (50 mg/kg) by oral gavage once monthly for 4 months, 31 or by ABT263 (41 μmol/kg) daily for 5 days, 105 lowered bone resorption, with maintained trabecular bone formation and enhanced cortical bone formation.31,32”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [31] Farr, 2017, Targeting cellular senescence prevents age-related bone loss in mice, Nat Med source

      Not checked in the free run.

    • cites [32] Kim, 2020, Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence, JCI Insight source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bone homoeostasis relies on a dynamic balance between osteogenesis, carried out by osteoblasts, and osteoclastogenesis, carried out by osteoclasts.

    “Bone homoeostasis relies on a dynamic balance between osteogenesis, carried out by osteoblasts, and osteoclastogenesis, carried out by osteoclasts.93”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [93] Cummings, 2002, Epidemiology and outcomes of osteoporotic fractures, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Acute senescence has beneficial effects and contributes to antifibrotic mechanisms in murine models of unilateral ureteral obstruction, which leads to tubular injury and subsequent renal fibrosis.

    “For example, acute senescence has been observed to have beneficial effects and to contribute to antifibrotic mechanisms in murine models of unilateral ureteral obstruction, which leads to tubular injury and subsequent renal fibrosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [103] Wolstein, 2010, INK4a knockout mice exhibit increased fibrosis under normal conditions and in response to unilateral ureteral obstruction, Am J Physiol Renal Physiol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Non-haematopoietic stromal cells, including osteoblasts and osteoprogenitor cells, promote the maintenance of haematopoietic stem cells.

    “Non-haematopoietic stromal cells, including osteoblasts and osteoprogenitor cells, promote the maintenance of haematopoietic stem cells.95”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [95] Morrison, 2014, The bone marrow niche for haematopoietic stem cells, Nature source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Compared with ABT263, PZ15227 was less toxic to platelets but was a more potent senolytic in vitro and in vivo.

    “Compared with ABT263, PZ15227 was shown to be less toxic to platelets, but was a more potent senolytic in vitro and in vivo.34”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] He, 2020, Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity, Nat Commun

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Senolytic drugs have shown promising results in the elimination of senescent cells and in alleviating various diseases in animal models.

    “In conclusion, senolytic drugs have shown promising results in the elimination of senescent cells and in alleviating various diseases in animal models (figure).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Given high expression of p16, dasatinib and quercetin treatment removed senescent macrophages, but was ineffective against senescent liver sinusoidal endothelial cells in mice.

    “Interestingly, given the high expression of p16, dasatinib and quercetin treatment removed senescent macrophages, but was ineffective against senescent liver sinusoidal endothelial cells in mice.111”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] Grosse, 2020, Defined p16High senescent cell types are indispensable for mouse healthspan, Cell Metab source

      Not checked in the free run.

65 of 65

  • The paper relies on this without support.

    UBX0101 failed a phase 2 study in patients with osteoarthritis in the knee.

    “However, the leading compound, UBX0101 (Unity Biotechnology, San Francisco, CA, USA), failed a phase 2 study in patients with osteoarthritis in the knee, a major setback for this early stage research into senotherapy.”

  • The paper relies on this without support.

    UBX0101 did not improve clinical symptoms in patients with osteoarthritis in the knee.

    “It is not known whether UBX0101 was able to remove senescent cells; however, the drug did not improve clinical symptoms.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Diabetic kidney disease pilot study has two patient counts

    Minor

    The paper describes a phase 1 pilot study using the same three-day dasatinib and quercetin regimen in patients with diabetic kidney disease, but gives its size as seven patients in one section and nine in another.

  • Figure reports reduced lung fibrosis despite unchanged fibrosis in the text

    Minor

    The figure attributes reduced fibrosis to dasatinib and quercetin (‡), citing study 37. The pulmonary section says fibrosis was visibly unaltered after that treatment in study 37.

2 of 2

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References 109 · Cited by 140

Research works printed but not linked: 1

  1. Meyer, 1996, Immune dysregulation in the aging human lung, Am J Respir Crit Care Med, 153, 1072, 10.1164/ajrccm.153.3.8630547 · DOI · Paper page

Authors
Raffaele, M., & Vinciguerra, M.
Affiliations
  • International Clinical Research Center, St. Anne's University Hospital Brno (CZ)
  • Medical University of Varna (BG)
Corresponding author
Vinciguerra, Manlio
ORCID
Venue
The Lancet Healthy Longevity
Publisher
Elsevier BV
Published
2022-01
Volume
3
Issue
1
Pages
e67-e77
ISSN
2666-7568 (ISSN-L)
DOI
10.1016/s2666-7568(21)00300-7
OpenAlex
W4211037299
Semantic Scholar
7f69480c3dd34b0eadb66917857302ea983b9233
Cited by
140
References
109
Citations by year
2026: 29 · 2025: 33 · 2024: 32 · 2023: 37 · 2022: 9
FWCI
3.89
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Healthy Longevity (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Liverpool John Moores University (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
European Regional Development Fund
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
senotherapeutics, cellular senescence, senolytics, senomorphics, senescence-associated secretory phenotype, age-related diseases, cardiometabolic disease, neurodegenerative diseases, cancer, adverse effects, off-label drug use, clinical trials
MeSH terms
Senotherapeutics, Aging, Animals, Cost-Benefit Analysis, Humans, Neoplasms, Cellular Senescence

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