| Thanks for reading The Abstract. This month’s edition is
1,721 words, about a
7-minute read.
|
|
Is there a topic that you’d like to see more of in
The Abstract? Drop us a line at
abstract@elysiumhealth.com. Want to get
The Abstract in your inbox? Sign up
here.
|
|
|
|
|
|
Welcome to the year’s final edition of
The Abstract. This one is a special edition: We’re covering the top 10 aging and longevity studies of 2024 as chosen by our expert team of scientists, including Elysium co-founder and renowned longevity researcher, Leonard Guarente, Ph.D. One unifying thread this year is that longevity is becoming a household word—some members of the media said longevity is replacing wellness as the new “it” word—and an ever-growing field of rigorous scientific research, with more human studies on promising compounds that target the pathways and mechanisms of aging.
“Aging research continued to push new boundaries in 2024, and Elysium was a major contributor with new clinical trials supporting the benefits of NAD+ boosting and homocysteine reduction in humans,” Dr. Guarente said.
“Given the momentum in human studies targeting aging, I am optimistic that the course of human health could be fundamentally changed.”
|
|
|
|
|
Basis and slower biological aging
|
|
|
|
|
|
|
Your daily Basis routine adds up. Based on epigenetic data, including from our TIME-A longevity study, taking Basis consistently for two or more years was associated with a ~5% slower rate of aging.* These individuals also had slower rates of aging of the liver, kidneys, and inflammation and metabolic systems.
|
|
|
|
|
|
|
|
*Compared to individuals who did not take Basis. The data is based on 473 participants who self-reported their supplement use. Biological age can also be influenced by various environmental and lifestyle factors and changes.
|
|
|
|
|
|
|
The top 10 longevity studies of 2024
|
|
These are third-party articles about science that we find interesting. Elysium’s products are not intended to screen, diagnose, treat, cure, or prevent any disease.
|
|
|
|
|
|
The state of human research on eight compounds
targeting aging
|
|
|
|
|
|
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)
|
|
|
| Dr. Guarente co-authored a high-profile review article in
Cell Metabolism about human trials exploring the most promising compounds that target pathways and mechanisms of aging: NAD+ precursors, metformin, glucagon-like peptide-1 receptor agonists (GLP-1RAs), TORC1 inhibitors, spermidine, senolytics, probiotics, and anti-inflammatories. These interventions were selected because: 1) they are well-represented in human clinical trials; 2) they’ve been shown to slow aging in preclinical studies; 3) they are thought to be safe for long-term use in humans; and 4) they target the hallmarks of aging. Dr. 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. His fellow authors in the study are 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 and ranked as one of the world’s most highly cited researchers for 11 consecutive years. (Cell Metabolism)
|
|
|
|
|
|
Nicotinamide riboside (NR-E) supports a healthy
inflammatory response in the lungs
|
|
|
Chronic obstructive pulmonary disease (COPD) is a progressive, incurable disease associated with smoking and advanced age and the third leading cause of death worldwide. In this study, a collaboration with researchers at University of Copenhagen and funded by a grant from the Danish government, we evaluated the effect of Elysium’s proprietary
nicotinamide riboside (NR-E) on clinical outcomes in elderly patients with COPD. Baseline
NAD+ levels were found to be lower in patients with COPD compared to lung-healthy controls and six weeks of oral supplementation with 2 g of NR-E increased NAD+ levels in whole blood by more than twofold. NR-E treatment significantly reduced levels of sputum IL-8, a major pro-inflammatory cytokine in COPD, and this effect persisted for 12 weeks after treatment. The results also showed indications of upregulated gene pathways associated with genomic integrity and reduced
epigenetic aging, which need to be confirmed in future trials. (Nature Aging)
|
|
|
|
|
|
Deactivating inflammatory protein boosts healthy
lifespan in mice
|
|
|
Targeting inflammation may be a way to increase healthspan, according to a study published in 2024. Interleukin-11 (IL-11) is a pro-fibrotic and pro-inflammatory protein that increases with age and is linked to cellular senescence and a variety of age-related conditions. In experiments in mice, researchers explored the impact of blocking IL-11 in two ways: by deleting genes related to the protein, and by administering a drug. Inhibition of IL-11 by either method resulted in increasing the median lifespan by more than 20% in both sexes. Both interventions improved biomarkers related to metabolism, frailty, and aging. (Nature)
|
|
|
|
|
|
Is radical life extension possible in the 21st
century?
|
|
|
Researchers investigated this question using data from regions with the longest lifespans. They discovered that life expectancy increased slowly until the 20th century, at which point advances in public health and medicine (e.g., sanitation and antibiotics) helped to increase life expectancy by three years per decade—what they call “radical life extension.” Life expectancies increased at a slower rate during the last 30 years, however, leading the study authors to conclude that radical life extension is implausible this century unless we discover ways to slow biological aging itself. Other scientists who commented on the study are more optimistic. Luigi Ferrucci, M.D., Ph.D., of the National Institute on Aging, said that delaying the onset of disease through preventative care could reduce damage related to the biology of aging. Steven Austad, Ph.D., professor of biology at the University of Alabama, Birmingham, remains convinced that
“a breakthrough in targeting the aging process itself” will lead to a human alive today living to 150. (Nature Aging)
|
|
|
|
|
|
Homocysteine levels are associated with
accelerated aging—and reversible
|
|
|
A research collaboration between Elysium and the University of Oxford found significant associations between homocysteine levels and rate of aging, suggesting that individuals with high levels of
homocysteine age at a faster rate. In the study,
Index revealed a deceleration in
biological aging in these participants following treatment with a specific combination of homocysteine-lowering B vitamins, developed at the University of Oxford and found in our brain health product
Matter. The results indicate that elevated homocysteine is causally associated with accelerated biological aging, and it’s the first research to suggest that this trend can be reversed. (Aging Cell)
|
|
|
|
|
|
Metabolic “signatures” for aging, extreme
longevity, and mortality
|
|
|
A study led by researchers at Tufts Medical Center analyzed the metabolomes of 2,764 people with family traits of extreme longevity to identify metabolic markers associated with aging, longevity, and mortality. They measured 408 metabolites and discovered subsets associated with each category, further grouping them into 19 "signatures" to differentiate those associated with damage from those that were beneficial. These signatures revealed potential connections between diet and longevity, with an emphasis on plant-based foods rich in ergothioneine (mushrooms and asparagus), flavones (celery and parsley), and salsolinol (dark chocolate). (Cell Reports)
|
|
|
|
|
|
Aging is sex-specific based on phenome-wide
associations
|
|
|
A study published in November used data from a cohort of 10,000 individuals aged 40–70 years to understand how aging patterns differ across body systems, environmental exposures, and between sexes. The participants were deeply phenotyped, meaning their data included clinical, physiological, behavioral, environmental, and multiomic parameters. The study uncovered sex-specific aging patterns with body systems aging differently in men and women. For example, higher
biological age scores based on bone density parameters were associated with low-bone-mass disorders and fractures in females, but not in males. The study has important implications for aging research and supports the need for a sex-specific approach to medicine. (Nature Aging)
|
|
|
|
|
|
CD38 regulates ovarian function and fertility via
NAD+ metabolism
|
|
|
The ovary is one of the first organs to age and this decline is associated with a decrease in
ovarian NAD+ levels. The cause, however, of this decrease is unclear. In a study in mice that was published near the end of 2023, researchers discovered that an NAD-consuming enzyme called CD38, which is expressed by immune cells in the ovarian extrafollicular space, increases with age and accelerates the decline of NAD+, contributing to a loss of fertility. The study suggests that interventions targeting CD38 may have therapeutic value for slowing ovarian aging, though to-date there is not yet evidence that this animal study can be extrapolated to humans. (iScience)
|
|
|
|
|
|
GLP-1 agonists reduce inflammation
|
|
|
Anti-obesity drugs show incredible promise for supporting weight loss and treating diabetes. These GLP-1 receptor agonists (GLP-1RAs)—semaglutide, marketed as Wegovy and Ozempic, and tirzepatide, marketed as Mounjaro and Zepbound—also have another benefit: They suppress inflammation in a variety of organs and tissues. Earlier this year, researchers discovered that the process is mediated by the brain. In the study, they found that GLP-1RAs reduce levels of the inflammatory molecule TNF-α triggered by certain immune signals. Using a model of severe infection, the drugs used brain receptors to reduce sickness, hypothermia, systemic inflammation, and lung injury. The process involves specific brain-to-body signaling pathways using α1-adrenergic and opioid receptors and suggests a "gut-brain connection" where GLP-1RAs influence the brain to help control inflammation in the rest of the body.
(Cell Metabolism)
|
|
|
|
|
|
Metformin slows aging in male monkeys
|
|
|
A study published in
Cell explored the potential of the diabetes drug metformin to slow aging in 12 cynomolgus monkeys. Researchers evaluated the impact of daily metformin on aging over the course of 40 months (equivalent to 13 years for humans) by analyzing samples from 79 types of tissues and organs, and conducting physical examinations. Metformin slowed
biological aging in tissues from the the lung, kidney, liver, skin, and the brain’s frontal lobe, while reducing chronic inflammation. Researchers suggested that metformin's neuroprotective effects were mediated by the activation of NRF2, a transcription factor that regulates the cell’s response to stress. The team behind the study has launched a 120-person trial to test whether the drug delays aging in humans, too. (Cell)
|
|
|
|
|
|
|
|
|
|
|
TERM OF THE MONTH
|
|
Inflammation
|
|
/ˌɪn.fləˈmeɪ.ʃən/
|
|
|
|
Inflammation is the immune system’s local, short-term response to cellular damage by increasing blood flow and other repair-focused factors. In contrast, low-grade chronic inflammation, or inflammaging, is a “slow drip” response to widespread cellular damage caused by aging and chronic conditions that impairs the function of cells and organs—causing pain, swelling, and dysfunction.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
AGING 101
|
|
What is homocysteine and how does it impact healthspan?
|
|
|
|
|
|
|
|
|
Elevated levels of homocysteine have been linked with an increased risk of developing numerous health conditions. Learn how homocysteine impacts aging, heart and brain health, and get tips on managing levels with B vitamins for healthy aging. This article was written by Elysium’s medical director Samuel Ritter, M.D., who is board-certified in emergency medicine and a fellow of the American College of Emergency Physicians. (Read more)
|
|
|
|
|
|
|
|
