A new wave of research is exploring the potential of various drugs and natural compounds to slow down aging and combat age-related diseases. A comprehensive review by leading scientists Leonard Guarente, David A. Sinclair, and Guido Kroemer highlights eight promising interventions currently undergoing human trials. These trials could revolutionize how we think about aging, aiming to extend the healthy, active years of life.
The Eight Promising Interventions
- Metformin: Beyond Diabetes Management Metformin, a widely used drug for type 2 diabetes, has attracted significant interest for its potential to extend lifespan. It appears to work by affecting mitochondrial function, reducing inflammation, and altering the gut microbiome. Clinical trials are underway to investigate its effects on age-related diseases such as cardiovascular disease, cancer, and cognitive decline. Metformin is being tested not only in diabetics but also in non-diabetic individuals to evaluate its potential to prevent cardiovascular events and slow cognitive impairment. Preliminary results suggest that metformin may improve heart function and reduce markers of inflammation, but further research is needed to confirm these benefits.
- NAD+ Precursors: Rejuvenating Cells at the Molecular Level NAD+ precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are emerging as powerful tools in the fight against aging. These compounds boost NAD+ levels, a molecule critical for energy production and DNA repair. Human trials have shown that NAD+ precursors can improve insulin sensitivity, enhance muscle performance, and support cognitive function. Studies are also examining their potential in treating neurodegenerative diseases such as Parkinson’s and Alzheimer’s, where early results are promising. For instance, NAD+ boosters have demonstrated the ability to improve brain function, reduce inflammation, and enhance overall mitochondrial health, indicating a possible path toward slowing or reversing neurodegenerative processes.
- GLP-1 Receptor Agonists: From Diabetes Control to Cognitive Health Originally developed to manage diabetes, GLP-1 receptor agonists like liraglutide and semaglutide have shown unexpected benefits in treating age-related cognitive decline and cardiovascular diseases. By regulating glucose metabolism and promoting satiety, these drugs may help prevent metabolic syndrome—a key risk factor for aging. Clinical trials are currently underway to test their efficacy in preventing cardiovascular events, managing cognitive impairment, and even treating Parkinson’s disease. Studies have found that GLP-1 drugs may protect against neurodegeneration, improve memory, and reduce the risk of heart disease and stroke.
- TORC1 Inhibitors: Targeting the Aging Pathways TORC1 inhibitors such as rapamycin are among the most promising agents for extending lifespan. Rapamycin and its analogs have shown the ability to slow down aging by inhibiting the TORC1 pathway, which controls cell growth and metabolism. Human trials have indicated that TORC1 inhibitors can enhance the immune response, improve vaccine efficacy in older adults, and potentially reduce age-related skin aging. However, there are concerns regarding potential side effects, such as impaired wound healing and reduced muscle growth, which are still being investigated. Future trials aim to identify optimal dosing strategies that maximize benefits while minimizing risks.
- Spermidine: Enhancing Cellular Cleanup Spermidine, a naturally occurring compound, promotes autophagy, the process by which cells remove damaged components and regenerate new ones. Autophagy is crucial for maintaining cellular health, and its decline is a hallmark of aging. Human studies have shown that spermidine supplementation may improve cognitive function and reduce mortality rates. For example, trials have found a correlation between higher dietary intake of spermidine and better cognitive performance, increased brain volume, and lower mortality rates. Ongoing studies are exploring spermidine’s potential in treating heart failure and improving immune response in older adults.
- Senolytics: Eliminating Damaged Cells Senolytics are a new class of drugs designed to selectively eliminate senescent cells—damaged cells that accumulate with age and contribute to various diseases. Early clinical trials with senolytics such as dasatinib and quercetin have shown promising results in reducing the load of senescent cells, improving physical function, and lowering inflammation in patients with conditions like idiopathic pulmonary fibrosis and Alzheimer’s disease. The key challenge for senolytics is achieving sufficient specificity to target only senescent cells while leaving healthy cells intact. Researchers are optimistic about the potential of these drugs to enhance healthspan by reducing the harmful effects of cellular aging.
- Probiotics: The Gut-Brain-Aging Axis The human gut microbiome plays a significant role in health and aging. Probiotics, beneficial bacteria that promote a healthy gut environment, are being studied for their potential to reduce systemic inflammation and improve immune function. Several trials have shown that probiotics can enhance natural killer cell activity, boost T-cell production, and reduce levels of inflammatory markers. Probiotic interventions are also being tested for their ability to prevent cognitive decline, improve mental health, and even protect against neurodegenerative diseases such as Parkinson’s and Alzheimer’s.
- Anti-Inflammatories: Fighting “Inflammaging” Chronic, low-grade inflammation—often called “inflammaging”—is a major driver of age-related diseases. Anti-inflammatory drugs, including traditional agents like aspirin and newer monoclonal antibodies targeting specific inflammatory pathways, are being tested for their potential to mitigate these effects. Clinical trials are ongoing to evaluate their effectiveness in preventing cancer, cardiovascular diseases, and cognitive decline. For example, studies are investigating whether anti-inflammatory agents can prevent cancer recurrence, reduce the risk of myocardial infarction, and improve cognitive function in patients with mild Alzheimer’s disease.
The Path Forward
The outcome of these ongoing and future trials could pave the way for new anti-aging medicines that not only target specific age-related diseases but also have broader disease-preventing effects. As we await the results of these studies, there is hope that these interventions may soon be repurposed from their current disease-specific uses to address the underlying mechanisms of aging, potentially revolutionizing the field of geriatric medicine.
References
Guarente, L., Sinclair, D. A., & Kroemer, G. (2024). Human Trials Exploring Anti-Aging Medicines. Cell Metabolism, 36. https://doi.org/10.1016/j.cmet.2023.12.007
