The antagonistic pleiotropy of insulin‐like growth factor 1

Zhang, William B.; Ye, Kenny; Barzilai, Nir; Milman, Sofiya

doi:10.1111/acel.13443

Cited by 42 publications

(29 citation statements)

References 45 publications

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“…Evidence has indicated that individuals with low IGF-1 could fail to exert neuroprotection against oxidative stress and neuroinflammation in the brain as a neurotrophic factor [25], and thus the activity of the GH-IGF-1 axis declines progressively with advancing age may be mechanistically involved in AD pathogenesis [26,27]. As for IGF-1 dysregulation in a high direction, Zhang et al suggested that IGF-1 interacts with age to modify hazards for dementia [28]. While IGF-1 can protect against dementia in younger individuals, it is conversely associated with an increased risk of dementia in the elderly.…”

Section: Discussionmentioning

confidence: 99%

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Serum clinical laboratory tests and risk of incident dementia: a prospective cohort study of 407,190 individuals

Kuo

Liu

et al. 2022

Transl Psychiatry

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Prevention of dementia is a public health priority, and the identification of potential biomarkers may provide benefits for early detection and prevention. This study investigates the association of common serum laboratory tests with the risk of incident dementia. Among 407,190 participants from the UK Biobank (median follow-up of 9.19 years), we investigated the linear and nonlinear effects of 30 laboratory measures on the risk of all-cause dementia using Cox models and restricted cubic spline models. We found that dementia incidence was associated with low vitamin D concentration (hazard ratio 0.994, 95% confidence interval 0.993–0.996), indicators of endocrine disorders: IGF-1 level (P for non-linearity = 1.1E-05), testosterone level (P for non-linearity = 0.006); high sex-hormone-binding globulin level (HR 1.004, 95% CI: 1.003–1.006); reduced liver function: lower alanine aminotransferase (HR 0.990, 95% CI: 0.986–0.995); renal dysfunction: cystatin C level (P for non-linearity = 0.028); oxidative stress: lower urate level (HR 0.998, 95% CI: 0.998–0.999); lipids dysregulation: lower LDL (HR 0.918, 95% CI: 0.872–0.965) and triglycerides (HR 0.924, 95% CI: 0.882–0.967) concentrations; insulin resistance: high glucose (HR 1.093, 95% CI: 1.045–1.143) and HbA1c (HR 1.017, 95% CI: 1.009–1.025) levels; immune dysbiosis: C−reactive protein (P for non-linearity = 5.5E-09). In conclusion, markers of vitamin D deficiency, GH-IGF-1 axis disorders, bioactive sex hormone deficiency, reduced liver function, renal abnormalities, oxidation, insulin resistance, immune dysbiosis, and lipids dysregulation were associated with incident dementia. Our results support a contributory role of systemic disorders and diverse biological processes to onset of dementia.

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Section: Discussionmentioning

confidence: 99%

“…While IGF-1 can protect against dementia in younger individuals, it is conversely associated with an increased risk of dementia in the elderly. One possible mechanism is the inhibition of autophagy, which prevents core processes of repair and maintenance in the nervous system for older individuals [28].…”

Section: Discussionmentioning

confidence: 99%

Serum clinical laboratory tests and risk of incident dementia: a prospective cohort study of 407,190 individuals

Kuo

Liu

et al. 2022

Transl Psychiatry

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“…[37][38][39][40] Using samples from the UK Biobank of nearly 450,000 people, Milman's group found that lower IGF-1 levels in younger people were associated with an increased risk of mortality and age-related diseases compared with older adults. 41 These data suggest an interaction between age and IGF-1, where higher levels of IGF-1 appear to be protective for younger adults but not for older adults. Milman contributes these effects to antagonistic pleiotropy of IGF-1, which promotes development and growth in youth but antagonizes proteostasis and other cell maintenance mechanisms at older age 42 (Fig.…”

Section: Translational Geroscience: Role Of Igf-1 In Human Healthspan and Lifespanmentioning

confidence: 81%

Extending human healthspan and longevity: a symposium report

DeVito¹,

Barzilai

Cuervo

et al. 2021

Annals of the New York Academy of Sciences

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For many years, it was believed that the aging process was inevitable and that age-related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age-related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life. Experts in the field have made remarkable advancements in understanding the mechanisms underlying biological aging and identified ways to target aging pathways using both novel agents and repurposed therapies. While geroscience researchers currently face significant barriers in bringing therapies through clinical development, proof-of-concept studies, as well as earlystage clinical trials, are underway to assess the feasibility of drug evaluation and lay a regulatory foundation for future FDA approvals in the future.

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“…IGF-1 levels in vivo are regulated by GH, and IGF-1 also has a negative feedback regulation on GH secretion (161,162). Studies have shown that IGF-1 has important effects on the healthy growth and function of cells and tissue in model organisms (163)(164)(165). GH can not only directly affect human oocytes and cumulus cells but also indirectly influence oocyte quality and maintain oocyte DNA integrity by activating IGF-1 synthesis or promoting ovarian steroidogenesis (166-168).…”

Section: Gh/igf-1 Axis Interventionsmentioning

confidence: 99%

Aging conundrum: A perspective for ovarian aging

Liu

Song

et al. 2022

Front. Endocrinol.

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Progressive loss of physiological integrity and accumulation of degenerative changes leading to functional impairment and increased susceptibility to diseases are the main features of aging. The ovary, the key organ that maintains female reproductive and endocrine function, enters aging earlier and faster than other organs and has attracted extensive attention from society. Ovarian aging is mainly characterized by the progressive decline in the number and quality of oocytes, the regulatory mechanisms of which have yet to be systematically elucidated. This review discusses the hallmarks of aging to further highlight the main characteristics of ovarian aging and attempt to explore its clinical symptoms and underlying mechanisms. Finally, the intervention strategies related to aging are elaborated, especially the potential role of stem cells and cryopreservation of embryos, oocytes, or ovarian tissue in the delay of ovarian aging.

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The antagonistic pleiotropy of insulin‐like growth factor 1

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 42 publications

References 45 publications

Serum clinical laboratory tests and risk of incident dementia: a prospective cohort study of 407,190 individuals

Serum clinical laboratory tests and risk of incident dementia: a prospective cohort study of 407,190 individuals

Extending human healthspan and longevity: a symposium report

Aging conundrum: A perspective for ovarian aging

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