Vitamin D3 promotes longevity in Caenorhabditis elegans

Huggins, Billy; Farris, Mindy

doi:10.1007/s11357-022-00637-w

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…Twenty years ago, the National Institute on Aging (NIA, USA) launched an Intervention Testing Program (ITP) dedicated to identifying longevity candidates in a genetically heterogeneous mouse model (candidates are evaluated in three independent laboratories) [22]. The ITP has identified two longevity drug candidates, the immunosuppressant rapamycin [23] and the antidiabetic acarbose [24] that are currently under clinical investigation [3]. Vitamin D and the antidiabetic drug metformin have been identified in other animal models and are also under clinical investigation [3,25].…”

Section: Longevity Candidatesmentioning

confidence: 99%

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

Garay

2024

Explor Drug Sci

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Five families of investigational products are in clinical investigation to slow or reverse normal aging processes [longevity candidates, mesenchymal stem cells, senolytics drugs, sirtuin activators, and nicotinamide adenine dinucleotide (NAD)+ precursors]. The longevity candidates, vitamin D and metformin, appear to significantly reduce all-cause mortality and prolong life expectancy. This should be confirmed by interventional studies. The mesenchymal stem cell family is the most advanced in clinical trial development [phase 2b randomized controlled trial (RCT)]. An allogeneic bone marrow stem cell preparation (Lomecel-B) reduced locomotor frailty in older people. The improvement in locomotion was modest. In the future, attempts could be made to improve potency through a precondition or genetic modification of naive bone marrow stem cells. Autologous adipose stem cell-assisted fat grafting increased graft survival, facial volume, and skin quality. The association of the senolytic drugs dasatinib and quercetin was well tolerated, with low brain penetration of dasatinib and undetectable levels of quercetin. The sirtuin-1 activator resveratrol (combined with physical exercise) improved physical function in older adults with physical limitations. The NAD+ precursor nicotinamide riboside improved physical exercise performance. In conclusion, Lomecel-B is the most advanced agent in clinical trial development for normal aging processes (phase 2b for locomotion frailty), followed by resveratrol and nicotinamide riboside.

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Section: Longevity Candidatesmentioning

confidence: 99%

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

Garay

2024

Explor Drug Sci

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“…All animals received a rescue diet throughout their lives, enriched with calcium (2%), phosphorus (1.25%), and lactose (20%) (8852-S010, SM Rescue Diet VDR KO, ssniff Spezialdiäten GmbH, Soest, Germany) to ensure normalized calcium homeostasis [42,52]. The mice had ad libitum access to chow and water and were kept in a specific pathogen-free facility at constant temperature (19)(20)(21)(22) • C) with a 12/12 light/dark cycle. All procedures were conducted according to the guidelines of Hungarian Law of Animal Protection (XXVIII/1998), and were approved by the National Scientific Ethical Committee on Animal Experimentation (PE/EA/00487-6/2021, approval date: 9 November 2021).…”

Section: Animalsmentioning

confidence: 99%

“…Cerebrovascular diseases and consequential vascular cognitive impairment represent a significant global burden, ranking among the leading causes of death and disability in older adults [ 1 , 2 ]. In addition to well-established risk factors such as hypertension [ 3 ], obesity [ 4 , 5 , 6 ], endocrine disorders [ 7 , 8 , 9 , 10 ], systemic atherosclerosis [ 11 , 12 ] and diabetes mellitus [ 13 , 14 , 15 , 16 , 17 ], growing evidence suggests that vitamin D deficiency (VDD) plays a crucial role as an emerging cardiovascular risk factor in age-related cerebrovascular pathologies [ 18 , 19 , 20 , 21 ]. The incidence of VDD has been on the rise in recent years, affecting a substantial proportion of the population, particularly in regions with limited sun exposure and inadequate dietary vitamin D intake [ 22 , 23 , 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Disruption of Vitamin D Signaling Impairs Adaptation of Cerebrocortical Microcirculation to Carotid Artery Occlusion in Hyperandrogenic Female Mice

Nagy,

Hricisák,

Walford

et al. 2023

Nutrients

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Vitamin D deficiency contributes to the pathogenesis of age-related cerebrovascular diseases, including ischemic stroke. Sex hormonal status may also influence the prevalence of these disorders, indicated by a heightened vulnerability among postmenopausal and hyperandrogenic women. To investigate the potential interaction between sex steroids and disrupted vitamin D signaling in the cerebral microcirculation, we examined the cerebrovascular adaptation to unilateral carotid artery occlusion (CAO) in intact, ovariectomized, and hyperandrogenic female mice with normal or functionally inactive vitamin D receptor (VDR). We also analyzed the morphology of leptomeningeal anastomoses, which play a significant role in the compensation. Ablation of VDR by itself did not impact the cerebrocortical adaptation to CAO despite the reduced number of pial collaterals. While ovariectomy did not undermine compensatory mechanisms following CAO, androgen excess combined with VDR inactivity resulted in prolonged hypoperfusion in the cerebral cortex ipsilateral to the occlusion. These findings suggest that the cerebrovascular consequences of disrupted VDR signaling are less pronounced in females, providing a level of protection even after ovariectomy. Conversely, even short-term androgen excess with lacking VDR signaling may lead to unfavorable outcomes of ischemic stroke, highlighting the complex interplay between sex steroids and vitamin D in terms of cerebrovascular diseases.

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Geroprotective potential of microbiome modulators in the Caenorhabditis elegans model

Miller,

Mathai,

Yadav

et al. 2023

GeroScience

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Aging is associated with cellular and physiological changes, which significantly reduce the quality of life and increase the risk for disease. Geroprotectors improve lifespan and slow the progression of detrimental aging-related changes such as immune system senescence, mitochondrial dysfunction, and dysregulated nutrient sensing and metabolism. Emerging evidence suggests that gut microbiota dysbiosis is a hallmark of aging-related diseases and microbiome modulators, such as probiotics (live bacteria) or postbiotics (non-viable bacteria/bacterial byproducts) may be promising geroprotectors. However, because they are strain-specific, the geroprotective effects of probiotics and postbiotics remain poorly understood and understudied. Drosophila melanogaster, Caenorhabditis elegans, and rodents are well-validated preclinical models for studying lifespan and the role of probiotics and/or postbiotics, but each have their limitations, including cost and their translation to human aging biology. C. elegans is an excellent model for large-scale screening to determine the geroprotective potential of drugs or probiotics/postbiotics due to its short lifecycle, easy maintenance, low cost, and homology to humans. The purpose of this article is to review the geroprotective effects of microbiome modulators and their future scope, using C. elegans as a model. The proposed geroprotective mechanisms of these probiotics and postbiotics include delaying immune system senescence, preventing or reducing mitochondrial dysfunction, and regulating food intake (dietary restriction) and metabolism. More studies are warranted to understand the geroprotective potential of probiotics and postbiotics, as well as other microbiome modulators, like prebiotics and fermented foods, and use them to develop effective therapeutics to extend lifespan and reduce the risk of debilitating aging-related diseases.

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Vitamin D3 promotes longevity in Caenorhabditis elegans

Cited by 4 publications

References 36 publications

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

Disruption of Vitamin D Signaling Impairs Adaptation of Cerebrocortical Microcirculation to Carotid Artery Occlusion in Hyperandrogenic Female Mice

Geroprotective potential of microbiome modulators in the Caenorhabditis elegans model

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