Coenzyme Q10 (CoQ10)

Coenzyme Q10 plays a vital role in mitochondrial energy production, which naturally declines with age. CoQ10 also acts as a potent antioxidant and anti-inflammatory agent, particularly in cardiovascular tissues. A randomized controlled trial found that CoQ10 combined with selenium significantly reduced cardiovascular mortality in older adults by approximately 50%. This effect persisted even after the intervention ended, suggesting lasting benefits from supplementation. In patients with type 2 diabetes and kidney disease, CoQ10 has been shown to improve glycemic control and renal function.

These findings indicate that CoQ10 may not only support heart and metabolic health but also extend healthspan by mitigating age-related organ dysfunction.

Metformin

Originally developed as a treatment for type 2 diabetes, metformin has emerged as one of the most researched pharmaceuticals in aging science. It improves insulin sensitivity and reduces systemic inflammation and oxidative stress. Epidemiological studies have shown that people with diabetes who take metformin often live longer than even healthy control groups who do not take the drug. This paradoxical finding prompted the TAME (Targeting Aging with Metformin) trial, designed to test whether metformin can delay the onset of age-related diseases in non-diabetic adults.

While definitive longevity outcomes from these trials are still pending, the metabolic improvements and reduction in chronic disease risk associated with metformin use offer strong support for its potential role in healthy aging.

Polyamines

Polyamines, including spermidine and spermine, are naturally occurring molecules involved in DNA stability, cellular repair, and gene regulation. In animal studies, oral supplementation with polyamines has been shown to extend lifespan by improving tissue function and reducing chronic inflammation. Polyamine levels decline with age, and their loss has been linked to impaired immune function and higher disease risk.

What makes polyamines particularly intriguing is that they can be increased not only through supplements but also by modulating gut bacteria with certain prebiotics and probiotics. Although human trials are still in early stages, the mechanistic depth of polyamines in aging biology is compelling.

Reishi Mushroom Extract (Polysaccharides)

Reishi mushrooms contain bioactive polysaccharides that appear to interact with longevity-related pathways, including the insulin/IGF-1 signaling cascade. In studies using Caenorhabditis elegans, a widely accepted model organism in aging research, a combination of Reishi polysaccharides and acetic acid extended lifespan by 30 to 40%. These compounds activate a gene called DAF-16, which is associated with stress resistance and enhanced cellular repair.

While these are early-stage findings in non-human models, they reveal a specific molecular mechanism through which Reishi extracts could influence aging, warranting further investigation in mammals and humans.

Lipid-Based Supplements

Lipids are often viewed only through the lens of heart disease, but certain lipid molecules may promote healthy aging by maintaining cell membrane function and modulating gene expression. Supplementation studies in C. elegans show that adding specific lipids to the diet can significantly extend lifespan by regulating fat metabolism and activating protective genetic pathways.

Although more human data is needed, these results suggest that not all dietary fats are harmful and that some may be integral to cellular resilience in aging.

Vitamin D

Vitamin D is well known for its role in bone health, but emerging data suggests it may also influence longevity. Low levels of vitamin D have been linked to increased risk of cardiovascular disease, cognitive decline, and mortality. Two ongoing mega-trials involving more than 5,000 participants are investigating whether vitamin D supplementation can reduce all-cause mortality and delay the onset of chronic illness in older adults.

While final results are still pending, observational studies already support maintaining adequate vitamin D levels as a foundational element of healthy aging.

Branched-Chain Amino Acids (BCAAs)

BCAAs have primarily been studied for muscle maintenance, but recent research suggests they may also influence aging. In mice, supplementation with a BCAA-enriched mixture altered the plasma proteome, including upregulation of apolipoprotein A-I, a protein linked to cardiovascular protection. These changes may contribute to healthier aging, though human data remains limited.

Importantly, BCAAs must be balanced with other nutrients to avoid potential metabolic strain, particularly in people with kidney issues.

Antioxidant Blends and Mixed Results

Despite strong theoretical support, not all antioxidant supplements have proven effective in clinical trials. One well-designed human study tested a combination of ten popular supplements including resveratrol, green tea extract, curcumin, and fish oil over six months in healthy adults. The trial found no significant improvements in metabolic or cardiovascular markers, underscoring the importance of targeted interventions rather than supplement megadoses.

This finding serves as a reminder that more is not always better, and that supplements should be chosen based on individual needs and quality evidence.

A Targeted Approach to Healthy Aging

Longevity supplements hold promise, but they are not magic pills. The most effective strategies combine evidence-backed supplementation with healthy lifestyle practices such as a balanced diet, physical activity, and sleep. Some compounds like CoQ10 and metformin have shown significant results in extending lifespan or reducing disease risk. Others, such as polyamines and Reishi polysaccharides, show potential based on solid preclinical data.

The future of longevity science lies in identifying combinations of interventions, both lifestyle and pharmacological, that work synergistically. Supplements may play an important role in this mix, especially when they are chosen based on strong scientific evidence and individual health needs. For patients considering longevity supplements, we recommend sourcing these products through trusted platforms like Fullscript.