Researchers in Japan investigated whether lifelong supplementation with PQQ or IPQ could influence lifespan and healthspan. They also examined whether starting PQQ or IPQ supplementation in middle age could improve muscle function and reduce age-related fat accumulation.
“The mice that consumed PQQ as part of their diet not only lived longer as a group but also stayed more physically active and maintained better neuromuscular function as they aged,” Atsushi Sugimoto, assistant manager at Mitsubishi Gas Chemical, said.
“Importantly, the results showed that PQQ supported a longer healthy lifespan, not just survival, which is a key distinction in aging research.”
PQQ–IPQ conversion and cellular activity
PQQ acts as a strong antioxidant, helps stimulate the formation of new mitochondria, and supports normal brain function. IPQ forms when PQQ reacts with glycine during a chemical conversion process.
Although IPQ no longer retains the redox activity of PQQ, it still maintains many similar biological effects in living systems.
The researchers therefore suggested that the transformation from PQQ to IPQ would not eliminate its biological activity and may instead shift how it interacts with cellular pathways.
Inside the experiment
The researchers used senescence-accelerated mouse prone 8 (SAMP8) mice in the new study, as they have a short lifespan and develop age-related conditions such as memory impairment and sarcopenia that resemble those seen in older adults.
The researchers housed mice under controlled conditions with free access to food and water and conducted two experiments to test either lifelong or midlife supplementation.
In the first experiment, they randomly assigned mice shortly after weaning to receive either a control diet or diets containing 0.02% PQQ or 0.02% IPQ throughout life. In the second experiment, they started supplementation in middle-age (around seven months old), feeding them the same PQQ or IPQ diets for 16 weeks.
The researchers assessed physical aging based on the overall physical appearance of the mice every 3–4 months using a standardized aging scale, and assessed muscle function across whole-body muscular endurance, strength, and maximal muscular force.
For blood analysis, researchers collected small blood samples and measured glucose, triglycerides, HDL cholesterol, total cholesterol, and β-ketone levels. They also collected liver and adipose tissues to evaluate fat accumulation, measure liver fatty-acid oxidation activity, and investigate molecular changes by quantifying protein levels in muscle and liver tissues.
PQQ and IPQ supplementation improves healthy aging markers
Results showed that lifelong supplementation with both PQQ and IPQ improved healthy aging markers in mice with both compounds reducing midlife mortality, delayed visible signs of aging, and preserved muscle function.
Mice receiving PQQ or IPQ maintained healthier coats and also showed fewer signs of physical aging as they grew older, and slowed age-related declines in muscle performance, particularly in tests measuring endurance, coordination and neuromuscular function.
Despite muscle function declining by 30–50% in middle-aged mice, results showed that both PQQ and IPQ restored muscle performance to levels similar to those seen in young mice after six weeks.
The researchers also observed differences in fat metabolism. PQQ appeared to help maintain healthy fat stores, which may support survival in older age. In contrast, IPQ reduced fat accumulation, particularly in the liver.
“PQQ and IPQ improve age-related changes regardless of whether intake begins in early or middle age, although intake from early age is particularly effective in diminishing mortality risk during midlife,” wrote the researchers.
The researchers suggested that PQQ and IPQ may combat aging by reducing ‘inflammaging’, noting that PQQ’s anti-inflammatory effects could be due to its ability to suppress NF-κB, a key regulator of inflammatory responses.
“In the current study, PQQ and IPQ intake may have contributed to suppressing the decline in survival rates and improving muscle function in middle-aged individuals by reducing systemic inflammatory responses, including those in the muscles,” the researchers wrote.
They also noted that PQQ could protect mitochondria as it acts as an antioxidant, reducing oxidative stress inside cells, and although IPQ is less researched, some studies show that it can protect nerve and liver cells from oxidative damage and increase the production of PGC-1α, a protein that promotes mitochondrial synthesis.
“Although no lifespan-promoting effect was observed for IPQ in C. elegans, the reduction in middle-age mortality in mice may be related to the indirect protective effects of PQQ and IPQ against cytotoxic stress,” the researchers wrote.
They noted that PQQ and IPQ likely acted through different mechanisms from each other, explaining that PQQ improves muscle performance throughout life but does not change the rate at which muscle function declines, while IPQ mainly slowed the age-related decline itself.
In previous nematode research, IPQ showed little effect on lifespan while PQQ significantly extended it, likely due to its redox properties, which IPQ lacks.
“In our mouse experiments, although there were differences in the degree of lifespan-extending effects between PQQ and IPQ, both effectively suppressed the decline in early survival rates, suggesting that the mechanisms underlying lifespan regulation differ between nematodes and mammals, and the existence of a lifespan-promoting mechanism that does not solely depend on redox reactions,” the researchers noted.
They added that further research is needed to determine the optimal dosage, long-term safety, and detailed mechanism of action of PQQ and IPQ before they can be prescribed to maintain a healthy lifespan.
Source: Food & Function; doi: 10.1039/D6FO00788K “Pyrroloquinoline quinone and imidazopyrroloquinoline intake diminish mortality risk during midlife and improve muscular dysfunctions with age in mice.” Authors: Odera, K. et al.
