AGE/DOSE
Aging & Longevity

David Sinclair and Colleagues Reveal 8 Anti-Aging Medicines Applicable to Humans

Based on human evidence, Harvard and MIT scientists determine the most promising anti-aging interventions, including NAD+ precursors, spermidine, and senolytics.

MIT’s Leonard Guarente, Ph.D. (image: amacad.org), Harvard’s David Sinclair, Ph.D. (image: buckinstitute.org), and University of Paris Descartes’ Guido Kromer, Ph.D., M.D. (image: createcures.org).
By Griffin Dean

The Eight Anti-Aging Medicines: 

  • Metformin: an anti-diabetes medication. 
  • NAD+ precursors (e.g. NMN and NR): a class of molecules that increase NAD+ levels and activate pro-longevity enzymes called sirtuins. 
  • GLP-1 receptor activators (e.g. Ozempic): a class of compounds used as anti-diabetes medications. 
  • Rapamycin: an immune-modulating medication that inhibits protein synthesis and cell growth. 
  • Spermidine: a molecule that triggers autophagy — a cellular process that recycles mitochondria and proteins. 
  • Senolytics: a class of compounds that eliminate senescent cells — cells that accumulate with aging and promote the development of high-mortality chronic diseases. 
  • Probiotics: various species of bacteria that enhance the growth of beneficial gut bacteria while reducing the growth of toxic bacteria.
  • Anti-inflammatories (e.g. aspirin): compounds that reduce body-wide inflammation. 

Loads of animal studies have given credence to so-called anti-aging interventions — interventions that slow aging. However, whether such interventions work in humans is another question. 

Now, elite researchers from the Massachusetts Institute of Technology (MIT), Harvard Medical School, and the University of Paris Descartes have compiled a list of medicines with anti-aging effects in humans. 

As recently published in the high-profile journal Cell Metabolism, the basis for which the anti-aging medicines were chosen are as follows:

  • Well represented in completed or ongoing clinical trials — human studies where the intervention is controlled. 
  • Solid catalog of animal research. 
  • Sufficient evidence of safety in humans. 
  • Mitigate hallmarks of aging — biological drivers of aging. 

Interventions not included: 

  • Non-pharmacological interventions like diet and exercise. 
  • Antioxidants. 
  • Too far from being tested in humans (e.g. cellular reprogramming).  
  • Promising but not enough data (e.g. SGLT2 inhibitors). 

Controlled Human Trials  

As part of their discussion, Guarente, Sinclair, and Kromer review what are called epidemiological studies, where large populations known to have received an intervention are studied and conclusions are made based on associations. However, in line with their own criteria, only clinical trials, which can infer cause and effect relationships will be summarized here.

Metformin

The clinical trials for this blood sugar-lowering drug suggest that it protects diabetic patients against heart failure. Metformin also seems to alter the gut microbiome, but it is unclear whether this alteration reduces body-wide inflammation — a major driver of aging — which probiotics and omega-3 fatty acids were shown to do in the same study. 

In non-diabetics, metformin may prolong the effects of flu vaccines by maintaining the survival of immune cells. However, it counteracts the benefits of aerobic exercise and resistance exercise in older adults. Suffice it to say, there is a lack of clinical evidence showing metformin’s anti-aging effects in non-diabetics. 

“Metformin is an extremely promising drug for slowing aging and increasing healthspan with manageable side effects,” say Guarente, Sinclair, and Kromer. 

NAD+ Precursors 

The NAD+ precursors NMN and NR have repeatedly been shown to raise blood NAD+ levels in clinical trials. NMN improves insulin signaling in prediabetic women while improving physical activity in middle-aged and older adults. NMN also lowers cholesterol, blood pressure, and weight in overweight individuals. 

NR improves symptoms of Parkinson’s disease in select patients and reduces amyloid β in Alzheimer’s disease patients, suggesting it protects against neurodegeneration. NR also improves the coordination of individuals with ataxia telangiectasia, a rare genetic disorder. 

When combined with pterostilbene — a compound found in blueberries, NR slows the progression of ALS, a.k.a. Lou Gehrig’s disease, and may protect against liver aging. Guarente, Sinclair, and Kromer say, as it pertains to kidney disease, cardiovascular disease, muscular dystrophy, infertility, and hearing loss, 

“These areas, along with other maladies accompanying aging, offer additional opportunities for exploration in ongoing and future human trials.”

GLP-1 Receptor Activators 

Ozempic — an anti-diabetes drug prescribed to patients who do not respond to metformin — has become all the rage in Hollywood for its weight loss capabilities. Indeed, clinical trials show that Ozempic leads to weight loss in both diabetic and non-diabetic individuals, which could protect against age-accelerating obesity. 

Ozempic is part of a class of drugs called GLP-1 receptor agonists (GRa), which activate GLP-1 receptors. In diabetics, GRas protect against kidney disease and reduce the risk of death from cardiovascular disease. 

GRas also counteract the symptoms of Parkinson’s disease while improving glucose metabolism in the brains of Alzheimer’s disease patients. Moreover, GRas improve the memory of prediabetics and diabetics alike. Taken together, these studies point to the role GRas in managing neurodegenerative diseases. Guarente, Sinclair, and Kromer conclude, 

“Altogether, it appears that GLP-1R agonists provide a major benefit through their capacity to induce weight loss and combat metabolic syndrome with little or no side effects.”

Rapamycin 

Rapamycin belongs to a class of drugs that inhibit a nutrient sensor in our cells called TORC1 (target of rapamycin complex 1). Topical application of rapamycin reverses aspects of skin aging, including thinning, collagen loss, and accumulation of senescent cells

The downside to rapamycin is that it reduces red blood cells and weakens wound healing in older adults. Rapamycin also blunts the effects of exercise, including muscle growth. Whether the TORC1 inhibitor everolimus — an advanced form of rapamycin — does this in humans is untested. 

Everolimus does, however, improve the effectiveness of flu vaccines in older adults, who usually have weakened immune systems. Considering that cell growth is needed to build muscle and heal wounds, Guarente, Sinclair, and Kromer say,

“It seems that the trick here might be to calibrate the system in a way that TORC1 inhibition is partial but optimal for reversing the aging effects of elevated TORC1 levels without interfering with necessary cell growth.”

Senolytics and Spermidine 

In patients with diabetic kidney disease, a combination of senolytics called dasatinib and quercetin (D+Q) reduces body-wide inflammation. In patients with a lung scarring disease, D+Q improves physical performance. With that being said, there are over 30 studies in the works that will test the effects of senolytics on age-related diseases like AD, arthritis, fatty liver, and diabetes/obesity. 

Spermidine has perhaps the least amount of clinical evidence supporting its anti-aging effects. Specifically, trials show that spermidine improves cognitive performance in older adults. Future spermidine trials will explore its capacity to reduce high blood pressure, treat heart failure, and improve vaccinations in older adults.  

Probiotics 

Clinical probiotic studies suggest these beneficial bacteria improve the immune system, reduce inflammation, and decrease the incidence of infection. Probiotics also protect against heart, kidney, and cognitive disease by lowering homocysteine levels.  

Probiotics lower fats circulating in the blood of individuals with high blood fat levels like obese children. They also improve insulin signaling, reduce inflammation, and protect against liver aging in overweight and obese adults.  

Probiotics also seem to improve cognitive performance in older adults and AD patients, though Guarente, Sinclair, and Kromer say “more corroboration is required,” and,

“Overall, probiotics offer considerable promise for improving human health. The further testing of probiotics for maladies of aging and diseases is well underway.”

Anti-inflammatories 

An anti-inflammatory compound called olamkicept alleviates the symptoms of irritable bowel disease (IBD). Olamkicept targets a pro-inflammatory molecule called IL-6, which tends to increase in humans with aging. However, an antibody called tocilizumab, which also targets IL-6 reduces immune cells and increases infections. 

Blocking IL-6 seemingly weakening the immune system may be the reason for ongoing clinical trials testing anti-inflammatories, such as aspirin, that target other pro-inflammatory molecules. Although, according to a large clinical trial, aspirin increases the risk of all-cause death in older individuals. Guarente, Sinclair, and Kromer say, 

“Care in dosing and treatment regimens may be important to avoid possible unwanted side effects.”

Should Anyone Actually Take These Anti-Aging Compounds?

“Given the momentum in human studies targeting aging, we are optimistic that the course of human health could be fundamentally changed. However, at this point no drug can be recommended for human use before its utility has been confirmed in convincing clinical trials.” — Guarente, Sinclair, and Kromer

Surprisingly, when it comes to these clinical trials, NAD+ precursors seem to have the most wide-ranging effects applicable to counteracting the aging process in humans. However, the lack of convincing evidence for most of these medicines begs for more clinical trials, which are on the way. So, in the future, we may see which medicines are most applicable to humans. Guarente, Sinclair, and Kromer and colleagues say,

“We believe that the next few years will present a tipping point, when the most viable approaches will become evident and move us toward a more widespread use of interventions targeting aging processes.”

Source

Guarente, L., Sinclair, D. A., & Kroemer, G. (2024). Human trials exploring anti-aging medicines. Cell Metabolism. https://doi.org/10.1016/j.cmet.2023.12.007

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