How healthy is the healthspan concept?

Kaeberlein, Matt

doi:10.1007/s11357-018-0036-9

Cited by 126 publications

(81 citation statements)

References 23 publications

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“…As we have discussed elsewhere, comparative intervention studies using the common marmoset can make significant strides towards translation of studies in mice towards application in human populations [9,32]. Certainly, studies testing the effects of compounds like acarbose and metformin on marmoset lifespan would be informative, but such long-term studies should also include more inclusive assessments of health or healthspan [33]. That is, it will be important to test whether acarbose or metformin (or even combination) will slow the physiological, functional and molecular changes associated with aging in mammalian species [34][35][36][37][38][39][40]…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the pharmacokinetics of metformin and acarbose in the common marmoset

Fernández

Ross

Liang

et al. 2019

Pathobiology of Aging & Age-related Diseases

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Metformin has beneficial effects on several age-related diseases (e.g., diabetes, obesity, cancer) and extends lifespan in nematodes and mice. Acarbose, an FDA-approved agent for treating type 2 diabetes, prevents breakdown of complex carbohydrates. Both compounds have been suggested as potential anti-aging interventions and acarbose has been shown to extend mouse longevity by the Intervention Testing Program (ITP). One potential next step is to assess the effect of these interventions on healthspan and lifespan in non-human primates. The common marmoset (Callithrix jacchus) is a small new world monkey with a relatively short life span and small size, both valuable for the translation potential of this nonhuman primate species for the study of aging and chronic disease. However, the dosing and assessment of potential side effects of either metformin or acarbose in this species have yet to be assessed. This study evaluated the pharmacokinetics of two dosage levels each of metformin or acarbose (given separately) in two small groups of young marmosets (n = 5/group) treated for 24 h to define the pharmacokinetics of each drug. The ability to rapidly and reliably dose socially housed marmosets with an oral form of acarbose or metformin that is well tolerated indicates that this species is a reliable model for testing acarbose and metformin in a safe and efficient way in a long-term intervention.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the pharmacokinetics of metformin and acarbose in the common marmoset

Fernández

Ross

Liang

et al. 2019

Pathobiology of Aging & Age-related Diseases

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show abstract

“…, biomarkers. At this point, it is still unclear what standard clinical laboratory testing might tell us in this case; however, longitudinal assessment of these same animals, as is planned, will help clarify whether age-related markers exist(Kaeberlein, 2018). In addition, expansion of potential markers such as epigenetic clock (Horvath & Raj, 2018), changes in the metabolome (Hoffman et al, 2016), frailty assessments (Kane, Gregson, Theou, Rockwood, & Howlett, 2017; Kim, Myers, Wyckoff, Cherry, & Jazwinski, 2017) or tests addressing cellular physiology (Salmon, Dorigatti, Huber, Li, & Nathanielsz, 2018) or others will be important to address during the course of this study.…”

Section: Discussionmentioning

confidence: 99%

Long‐term treatment with the mTOR inhibitor rapamycin has minor effect on clinical laboratory markers in middle‐aged marmosets

Sills

Artavia

DeRosa

et al. 2018

American J Primatol

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Interventions to extend lifespan and improve health with increasing age would have significant impact on a growing aged population. There are now several pharmaceutical interventions that extend lifespan in laboratory rodent models with rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) being the most well studied. In this study, we report on the hematological effects on a cohort of middle-aged common marmosets (Callithrix jacchus) that were enrolled in a study to test the effects of daily rapamycin treatment on aging in this species. In addition, we assessed whether sex was a significant factor in either baseline assessment or as an interaction with rapamycin treatment. Among our cohort at baseline, we found few differences in either basic morphology or hematological markers of blood cell counts, metabolism or inflammation between male and female marmosets. After dosing with rapamycin, surprisingly we found trough blood concentrations of rapamycin were significantly lower in female compared to male marmosets. Despite this pharmacological difference, both sexes had only minor changes in cellular blood counts after 9 months of rapamycin. These data then suggest that the potential clinical hematological side effects of rapamycin are not likely outcomes of long-term rapamycin in relatively healthy, middle-aged marmosets.

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“…For there to be the successful translation into the clinic, we cannot be limited to one or two criteria such as with life extension. The goal for human application should be to increase healthspan as well, where there is a ' period of life spent in good health, free from the chronic diseases and disabilities of aging' [11]. Indeed, the term 'health' in relation to aging could be considered as the capacity to tolerate and adapt to changing perturbations (robustness, resilience) [12].…”

Section: Selective Criteria and Classification Of Geroprotectorsmentioning

confidence: 99%

Is anti-ageing drug discovery becoming a reality?

Moskalev

2019

Expert Opinion on Drug Discovery

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How healthy is the healthspan concept?

Cited by 126 publications

References 23 publications

Evaluation of the pharmacokinetics of metformin and acarbose in the common marmoset

Evaluation of the pharmacokinetics of metformin and acarbose in the common marmoset

Long‐term treatment with the mTOR inhibitor rapamycin has minor effect on clinical laboratory markers in middle‐aged marmosets

Is anti-ageing drug discovery becoming a reality?

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