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Thanks for reading The Abstract. This month’s edition is
1,161 words, about a
4-minute read.
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Welcome to the New Year and the January
Abstract. We’re off to an exciting start already, with a new review article by Elysium chief scientist Leonard Guarente, Ph.D., published in the prestigious journal
Cell Metabolism. Guarente does a deep dive into the history and human clinical research related to eight compounds that target the hallmarks of aging. This month, we also cover the newfound relationship between vitamin B12 and tissue repair, biomarkers of cellular senescence that predict mortality, predictors of cardiovascular aging, and a two-year clinical trial of nicotinamide riboside for ataxia telangiectasia (a complex neurodegenerative disorder).
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Human Research on 8 Compounds Targeting Aging
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Eight interventions in human trials for aging and its attending diseases. Figure from Guarente et al., Human trials exploring anti-aging medicines, Cell Metabolism (2023)
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Elysium chief scientist Leonard Guarente, Ph.D., is a pioneering aging researcher and a mentor to several other experts in the field. In a recent issue of
Cell Metabolism, Guarente co-authored a review article about human trials exploring compounds that target pathways and mechanisms of aging along with David Sinclair, Ph.D., one of Dr. Guarente’s postdoctoral mentees and now a professor of genetics at Harvard Medical School, and Guido Kroemer, M.D., Ph.D., a professor at the Université Paris Cité. Guarente and his colleagues focus on eight drugs and compounds: metformin, NAD+ precursors, glucagon-like peptide-1 receptor agonists, TORC1 inhibitors, spermidine, senolytics, probiotics, and anti-inflammatories.
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These interventions made the list for four reasons: 1) they’re well-represented in ongoing or completed human clinical trials; 2) they’ve been shown to slow aging in preclinical studies; 3) they’re thought to be sufficiently safe for long-term use in humans; and 4) they work by targeting the hallmarks of aging. Guarente and his colleagues suggest that we’re nearing a tipping point and will soon understand which approaches are most effective, leading to their widespread use for targeting processes of aging.
“Given the momentum in human studies targeting aging, we are optimistic that the course of human health could be fundamentally changed,” they write.
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The Expert’s Take:
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“Studies of the biology of aging over the past three decades have led to interventions that can slow aging in laboratory organisms. Our review in Cell Metabolism examines results exploring the eight most promising interventions, including NAD+/sirtuins, in completed or ongoing human trials. The findings to date begin to illuminate how these interventions might slow the aging process, forestall or even treat aging-related diseases, and extend the healthy, active period of life in the near future.”
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Leonard Guarente, Ph.D.
Novartis Professor of Biology and director of the Paul F. Glenn Center for Biology of Aging Research at MIT and Elysium co-founder and chief scientist
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Not Just an NAD+ Booster
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Unlike traditional NAD+ boosters, Basis contains
two ingredients that activate your “longevity genes” by
two separate mechanisms. Together, they work synergistically to support healthy aging.
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THIS MONTH
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What We’re Reading
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These are third-party articles about science that we find interesting but have no relationship to Elysium or any of our products. Elysium’s products are not intended to screen, diagnose, treat, cure, or prevent any disease.
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Cellular Senescence Biomarkers Predict Mortality
The accumulation of senescent cells in tissues throughout the body is considered a driver of aging. Since senescent cells secrete a variety of often harmful factors—part of the senescence associated secretory phenotype (SASP)—researchers in this study investigated whether circulating concentrations of candidate SASP factors could predict mortality in older adults. They discovered that these biomarkers of cellular senescence improved the prediction of mortality beyond traditional demographic and clinical characteristics. The authors suggest that
“circulating concentrations of these proteins may reflect a fundamental mechanism of aging” and that
“biomarkers of cellular senescence [are] informative predictors of clinically important health outcomes in older adults, including death.” (Aging Cell)
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What Predicts Cardiovascular Aging?
Cardiovascular aging refers to the accumulation of damage to the heart, arteries, veins, capillaries, and even other related organ systems; it often results in cardiovascular disease, the leading cause of death globally. In this study, researchers combined machine learning approaches with cardiac magnetic resonance imaging and electrocardiogram data from 39,559 participants of the UK Biobank to predict cardiovascular age and determine the genetic and environmental associations with premature cardiovascular aging. They found that a progressive decline in both vascular and myocardial tissue compliance was the strongest predictor of accelerated cardiovascular aging. Importantly, they discovered that genetics accounts for only 10.5% of cardiovascular aging and that modifiable risk factors—hypertension, diabetes, and dyslipidemia, for example—all contribute to accelerated aging.
(Nature Communications)
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Long-Term Use of NR Supports Motor Coordination
Ataxia telangiectasia (A-T), or Louis-Bar syndrome, is a rare, inherited, complex neurodegenerative disorder. One of the underlying mechanisms of A-T is thought to be a defect in the DNA repair system. Previous research in animal models of A-T supported this idea, finding that NAD+ replenishment improved the healthspan and lifespan of worms in mice by upregulating DNA repair and mitophagy (the clearing of damaged mitochondria). In this study, researchers gave people with A-T the NAD+ precursor nicotinamide riboside (NR) at doses of 10 to 37 mg/kg per day for two years. All but one participant experienced an overall improvement in neuromotor scores, driven by improvements in aspects of motor coordination and eye movements.
(Movement Disorders)
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Vitamin B12 Enhances Tissue Repair and Rejuvenation
Cell reprogramming involves the loss of cellular identity and the acquisition of an embryonic stem cell-like state, which can be achieved by activating four genes. Transient reprogramming is under investigation as a potential therapeutic strategy for tissue regeneration and rejuvenation. The process, however, is poorly understood, with low efficiency and risk of teratoma and cancer development. In a new study, researchers discovered that cellular reprogramming in mice leads to global depletion of vitamin B12. Supplementation with B12 not only improved reprogramming efficiency but accelerated tissue repair in a mouse model of ulcerative colitis. The authors conclude that
“our results…highlight the possibility to safely administer B12 for the therapeutic enhancement of cellular plasticity for regenerative medicine, organ injury and repair.” Additional research is needed to determine if the results can be extrapolated to humans.
(Nature Metabolism)
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TERM OF THE MONTH
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Cellular Reprogramming
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/ ˈsel.jə.lər ˌriːˈprəʊ.ɡræm /
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Cellular reprogramming is a step-by-step scientific process of turning adult somatic cells into pluripotent or embryonic-like stem cells. The process was pioneered by Nobel Prize-winning scientist Shinya Yamanaka, whose “Yamanaka factors”—a mixture of the transcription factors Oct4, Sox2, KLF-4, and c-Myc (OSKM)—turn on gene expression pathways usually only activated in pluripotent stem cells. Cellular reprogramming changes and erases epigenetic markers such as DNA methylation.
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AGING 101
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What is NAD+ and Why Is it Important?
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NAD+ is found in every cell in your body and is essential for creating cellular energy and maintaining cellular health. Levels of this critical molecule correlate with health status in aging. Here’s why it’s so important, how it was discovered, and how you can get more of it. (Read More)
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