Coenzyme Q10
What is Coenzyme Q10?
Coenzyme Q10 (CoQ10) is a fat-soluble, vitamin-like quinone found in nearly all cell membranes, hence the name “ubiquinone.” It plays a pivotal biochemical role in cellular energy metabolism as a cofactor in the mitochondrial electron transport chain. Located in the inner mitochondrial membrane, CoQ10 shuttles electrons between Complexes I/II and Complex III, a step essential for ATP generation via oxidative phosphorylation (Genova & Lenaz, 2011). By facilitating electron transfer, CoQ10 helps maintain mitochondrial ATP production and cellular energy homeostasis. Equally important, CoQ10 serves as a potent antioxidant; in its reduced form (ubiquinol), it stabilises lipid membranes by preventing oxidative peroxidation of phospholipids and can regenerate other antioxidants, such as vitamin E and vitamin C (Littarru & Tiano, 2011). This dual role – bioenergetic and antioxidant – underpins its relevance to ageing biology, since mitochondrial dysfunction and oxidative stress are central drivers of cellular ageing (Lopez-Lluch et al., 2010).
Multiple lines of evidence suggest CoQ10’s levels and efficacy are linked to the ageing process. Human tissue studies indicate that endogenous CoQ10 concentrations reach their peak in early adulthood and decline progressively with age (Kalen et al., 1989 ; Mantle & Hargreaves, 2019). For example, an analysis of human organs revealed significantly lower CoQ content in older individuals compared to younger ones, indicating an age-related decline in CoQ10 biosynthesis or retention (Kalen et al., 1989). This decline may have functional consequences: CoQ10 depletion impairs mitochondrial respiration and ATP output, while elevating reactive oxygen species (ROS) production. The resulting bioenergetic deficit and oxidative damage can contribute to cellular ageing, tissue dysfunction, and age-related diseases (Barcelos & Haas, 2019). Conversely, maintaining or restoring CoQ10 levels is hypothesised to support healthier ageing by sustaining mitochondrial function and reducing oxidative injury. Below, we review how CoQ10 influences systemic ageing processes and longevity, and we examine evidence for its anti-ageing effects internally (in organs and metabolism) and externally (in skin ageing).
Age-Related Decline of CoQ10 Levels
Endogenous CoQ10 production and tissue levels tend to diminish with advancing age, which may predispose cells to energetic stress and oxidative damage. A substantial age-related decline in CoQ10 has been documented in both human and animal studies. In human tissues, the content of CoQ10 in the heart, skeletal muscle, kidney, and skin is markedly lower in older adults compared to younger cohorts (Kalen et al., 1989). One longitudinal analysis noted that CoQ10 levels in the epidermis steadily fall from young adulthood onward, with levels in a 77-year-old roughly 40% lower than in a twenty-year-old (Littarru & Tiano, 2011). The implications of this CoQ10 decline are significant: mitochondria in aged tissues become less efficient and more prone to leakage of electrons that form ROS, fueling a cycle of oxidative damage to mitochondrial DNA, lipids, and proteins (Lopez-Lluch et al., 2010). In the skin, for example, diminishing CoQ10 correlates with a shift to anaerobic metabolism in elderly dermal cells and the accumulation of oxidative stress markers. Notably, in a large clinical trial of older adults (age 70-88), baseline low CoQ10 status (along with low selenium) was associated with a higher risk of cardiovascular mortality, suggesting that CoQ10 insufficiency may be a biomarker or contributor to ageing-related decline (Alehagen et al., 2013). Together, these observations support the notion that CoQ10 depletion is a contributing factor to age-associated cellular dysfunction. Encouragingly, they also raise the possibility that CoQ10 supplementation in older individuals might replenish mitochondrial function and counteract some deleterious ageing processes – an idea tested in various studies discussed below.
Systemic Anti-Ageing Effects of CoQ10
Mitochondrial Function and Oxidative Stress
One of CoQ10’s primary anti-ageing roles is preserving mitochondrial health. By virtue of its central position in the respiratory chain, CoQ10 helps sustain efficient ATP production in aging mitochondria. Even a mild increase in intra-mitochondrial CoQ10 has been shown to enhance respiratory activity and ATP synthesis in cells (Blatt & Littarru, 2011). In aging models, CoQ10 supplementation often improves markers of mitochondrial function. For instance, in aged mice, dietary CoQ10 reversed age-related reductions in mitochondrial energy production in multiple tissues, including the liver and heart, while also lowering protein oxidation levels (Shetty et al., 2013). Age-dependent declines in mitochondrial membrane potential and electron transport capacity in senescent cells have been partially restored by CoQ10 treatment, effectively “rejuvenating” mitochondrial bioenergetics (Schniertshauer et al., 2018). By restoring electron transport efficiency, CoQ10 reduces the electron leakage that generates superoxide anions, thereby attenuating oxidative stress at its source.
In addition to preventing ROS generation, CoQ10 directly quells oxidative damage through its antioxidant action. CoQ10’s reduced form (ubiquinol) readily donates electrons to neutralize lipid peroxyl radicals and to regenerate oxidized antioxidants like α-tocopherol (vitamin E), thus protecting cell membranes and lipoproteins from peroxidation (Ernster & Dallner, 1995). Studies confirm that raising CoQ10 levels can bolster an organism’s overall oxidative defense. In a controlled trial on older humans, 4-year supplementation with CoQ10 (200 mg/day) plus selenium significantly reduced oxidative stress biomarkers compared to placebo (Alehagen et al., 2023). Similarly, topical CoQ10 application in human skin has been shown to decrease UVA-induced oxidative damage: in one study, CoQ10 lotion use led to a significant drop in UVA-triggered epidermal oxidation (measured by ultra-weak photon emission) after just 1–2 weeks (Lain et al., 2024). At the cellular level, CoQ10 protects mitochondria from oxidative injury – for example, pretreating human keratinocytes with CoQ10 prevented UV-induced depletion of cellular thiols and oxidative DNA strand breaks (Hoppe et al., 1999). These findings illustrate that CoQ10 can mitigate oxidative stress both by improving mitochondrial efficiency (thereby producing fewer radicals) and by scavenging the ROS that are produced. Given the centrality of oxidative damage in aging (Harman, 1956), the antioxidant support provided by CoQ10 is considered a key mechanism for its systemic anti-aging effects.
Anti-Inflammatory and Cellular Senescence Effects
Chronic, low-grade inflammation (“inflammaging”) is a hallmark of aging, and CoQ10 appears to exert anti-inflammatory effects that could counter this process. Mechanistically, CoQ10 supplementation has been shown to down-regulate pro-inflammatory signaling pathways. In vitro and animal studies indicate CoQ10 can inhibit the NF-κB pathway – a central mediator of inflammation – thereby reducing downstream cytokine production (Schmelzer et al., 2008). Schmelzer and colleagues demonstrated that adding CoQ10 to cultured cells suppressed NF-κB activity and led to lower levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In alignment with these molecular findings, human trials and meta-analyses have observed significant reductions in circulating inflammatory markers with CoQ10 supplementation. A meta-analysis of 17 randomized controlled trials found that CoQ10 intake significantly lowered C-reactive protein, IL-6, and TNF-α levels compared to placebo (Fan et al., 2018). These changes suggest a real anti-inflammatory benefit, as CRP and IL-6 are risk factors for many age-related pathologies (atherosclerosis, frailty, etc.).
CoQ10’s ability to modulate inflammation may also impact cellular senescence – the permanent growth arrest of cells that contributes to tissue aging. CoQ10 deficiency is associated with a pro-senescent phenotype, whereas repletion can oppose senescence. In human fibroblast studies, inhibiting CoQ10 biosynthesis accelerated cellular senescence, as evidenced by increased senescence markers and secretion of pro-inflammatory cytokines (the senescence-associated secretory phenotype, SASP). Remarkably, reintroducing CoQ10 to these CoQ10-deprived cells reversed many of these changes – reducing inflammatory cytokine secretion and restoring normal cell function (Marcheggiani et al., 2021). Likewise, in endothelial cells, CoQ10 prevented replicative senescence by improving mitochondrial function and reducing oxidative signaling that triggers cell-cycle arrest (Zhai et al., 2017). By tempering chronic inflammation and delaying the onset of cellular senescence, CoQ10 helps maintain tissue homeostasis in aging organs. These anti-inflammatory and “anti-senescent” properties contribute to its systemic anti-aging profile, potentially translating into preserved organ function and resilience against age-related diseases.
Cognitive and Neurological Function
Another domain where CoQ10 shows promise is in cognitive aging and neuroprotection. The brain is highly metabolically active and vulnerable to mitochondrial dysfunction and oxidative damage over time. CoQ10, being both an energy booster and antioxidant, has been investigated for supporting brain health in aging. In animal models, supplemental CoQ10 has yielded improvements in learning, memory, and brain oxidative status. For example, Shetty reported that old mice (aged ~18 months) fed a high CoQ10 diet for 15 weeks performed significantly better in spatial learning (Morris water maze efficiency) than age-matched controls. This cognitive improvement coincided with a decrease in oxidative damage in brain mitochondria of the CoQ10-treated mice (Shetty et al., 2013). Similarly, long-term CoQ10 administration in rodents has been shown to increase brain mitochondrial CoQ10 levels and protect neurons from toxin-induced degeneration, supporting its neuroprotective potential (Matthews et al., 1998).
In humans, direct evidence for CoQ10’s cognitive benefits in normal aging is still emerging. Large clinical trials in neurodegenerative diseases have had mixed results – notably, a high-dose CoQ10 trial in Parkinson’s disease did not show a significant clinical benefit (Beal, 2014), suggesting that CoQ10 alone may not reverse established neurodegeneration. However, in populations with mild cognitive impairment or early neurodegenerative changes, some smaller studies hint at benefits such as improved mental vitality or slower cognitive decline with CoQ10 supplementation (Hernández-Camacho et al., 2018). CoQ10’s effects on mitochondrial bioenergetics in the brain may underlie these observations: by enhancing ATP production and reducing oxidative damage in neurons, CoQ10 could help sustain synaptic and cognitive function as the brain ages. Moreover, CoQ10 might indirectly benefit cerebrovascular health (through its cardiovascular effects, see below), thereby improving brain perfusion and cognitive outcomes in older adults. While more research is needed for conclusive evidence in humans, the available data from animal models and mechanistic studies strongly suggest that CoQ10 is a supportive factor for cognitive longevity, helping to maintain neuronal energy supply and protect neural cells from age-related oxidative stress.
Cardiovascular Health and Longevity
Perhaps the most robust clinical evidence for CoQ10’s systemic anti-aging impact comes from studies on cardiovascular aging. The heart is an energy-demanding organ, and CoQ10 is concentrated in cardiac mitochondria to facilitate ATP production for continual pumping. With age, CoQ10 levels in the heart muscle decline, which may contribute to reduced cardiac efficiency and increased vulnerability to stress (Mantle & Hargreaves, 2019). Supplementing CoQ10 in older adults has demonstrated notable cardioprotective effects. In a landmark randomized controlled trial on 443 elderly individuals (average age 78), supplementation with CoQ10 (200 mg/day) plus selenium for 4 years resulted in a 54% reduction in cardiovascular mortality compared to placebo (Alehagen et al., 2023). This long-term study (known as the KiSel-10 trial) also found improved cardiac function on echocardiography and lower levels of N-terminal proBNP (a heart failure biomarker) in the CoQ10-treated group (Alehagen et al., 2023). Impressively, a follow-up analysis showed that the CoQ10-selenium group continued to have lower cardiovascular death rates even 10-12 years after the trial, indicating a lasting impact on cardiovascular health and survival (Alehagen et al., 2023). These findings suggest that CoQ10 can delay cardiac aging and reduce heart disease risk in the elderly, likely by improving myocardial energy metabolism and reducing oxidative damage in cardiac cells.
Beyond mortality, CoQ10 improves other aspects of age-related cardiovascular function. A sub-analysis of the KiSel-10 study found that CoQ10 supplementation favorably influenced age-related biomarkers linked to vascular aging and inflammation. Specifically, after 48 months, the CoQ10 (with selenium) group had significantly lower levels of adhesion molecules and cytokines (e.g., ICAM-1, adiponectin, osteoprotegerin) compared to rising levels in the placebo group, reflecting a reduction in endothelial dysfunction and inflammatory activity (Alehagen et al., 2023). Additionally, CoQ10 has been shown to enhance endothelial function in older adults by increasing nitric oxide availability and reducing oxidative stress in vessels, thereby improving arterial compliance and blood pressure regulation (Littarru & Tiano, 2011). In patients with existing heart failure (an age-associated condition), the Q-SYMBIO trial demonstrated that a 2-year course of CoQ10 (300 mg/day) led to ~40% lower risk of major adverse cardiac events and improved symptoms, highlighting CoQ10’s therapeutic value in an aging cardiovascular system (Mortensen et al., 2014). Overall, these human studies strongly indicate that CoQ10 promotes cardiovascular longevity – it helps maintain a healthier heart and blood vessels in aging populations, contributing to reduced cardiovascular mortality and potentially extending healthspan. Given that cardiovascular disease is a leading cause of death in older adults, CoQ10’s benefits in this arena make it a compelling anti-aging intervention candidate.
Topical CoQ10 and Skin Anti-Ageing Benefits
In addition to its internal, systemic effects, CoQ10 has garnered attention as a topical agent for skin anti-aging. The skin’s aging process is driven by both intrinsic factors (chronological aging, oxidative stress) and extrinsic factors (UV radiation, pollution), which together lead to collagen breakdown, thinning of the dermis, fine lines, wrinkles, and dryness. CoQ10 is naturally present in the skin, where it supports cellular energy production for dermal maintenance and acts as a first-line antioxidant in the epidermis. However, cutaneous CoQ10 levels, much like in other tissues, diminish with age and UV exposure, contributing to reduced cellular repair and heightened oxidative damage in older skin. Topical replenishment of CoQ10 has been explored as a strategy to mitigate skin aging, and a growing body of research supports its efficacy for improving skin appearance and health.
Penetration and Mechanisms: Early studies established that CoQ10 can penetrate into living skin layers when applied topically. Hoppe showed that a CoQ10-containing cream penetrated the human stratum corneum and reached the deeper epidermal layers to exert biological effects. In that study, CoQ10 treatment significantly reduced oxidation levels in the skin (measured by decreased UVA-induced photon emissions) and protected dermal fibroblasts from oxidative DNA damage (Hoppe et al., 1999). CoQ10 was also found to suppress collagen-degrading enzymes: Hoppe reported that UVA-exposed fibroblasts had markedly lower collagenase (matrix metalloproteinase-1) expression when pretreated with CoQ10, indicating protection of collagen integrity (Hoppe et al., 1999). These mechanistic insights have been confirmed by subsequent research. For example, Inui demonstrated that CoQ10 can inhibit the UVB-induced signaling that leads to skin matrix degradation: CoQ10 reduced the secretion of interleukin-6 from keratinocytes after UV exposure, which in turn lowered the induction of MMP-1 and MMP-3 in fibroblasts and ultimately prevented collagen breakdown (Inui et al., 2008). In cellular studies, CoQ10 also boosts the metabolic activity of skin cells – increasing mitochondrial ATP production in aging keratinocytes – thereby promoting more robust cell repair and turnover (Schniertshauer et al., 2018). Collectively, these findings highlight CoQ10’s dual action in skin: it energizes skin cells for maintenance and repair, and it shields the skin’s structural proteins from oxidative and inflammatory damage.
Clinical Skin Anti-Aging Evidence: The mechanistic benefits of CoQ10 translate into visible improvements in skin aging parameters. Notably, wrinkle reduction with topical CoQ10 has been documented in multiple trials. In a seminal study, it was found that six months of CoQ10 cream application around the eyes significantly reduced wrinkle depth in 20 subjects, with no irritation or adverse effects reported (Hoppe et al., 1999). A later placebo-controlled study by Inui using a 1% CoQ10 cream confirmed a decrease in wrinkle grade after five months, as evaluated by dermatologists – treated participants showed smoother skin and shallower wrinkles compared to baseline (Inui et al., 2008). Another clinical trial reported that a CoQ10-containing cosmetic used over 4 weeks led to continuous improvement in skin roughness and a decrease in fine lines, whereas the untreated control areas experienced slight worsening of wrinkles with time (Knott et al., 2015). Beyond wrinkles, CoQ10 benefits other hallmarks of skin aging: it has been shown to improve skin elasticity and hydration. In a study of middle-aged women, daily application of a CoQ10-rich formula for 4–8 weeks increased skin hydration levels and improved elastic rebound (as measured by a cutaneous elastometer), suggesting enhanced dermal moisture retention and collagen function. Importantly, these improvements correspond with underlying biochemical changes – increased dermal collagen density and fibroblast number have been observed in skin biopsies after topical CoQ10 treatment, indicating real structural anti-aging effects (Ayunin et al., 2022).
CoQ10’s excellent safety profile makes it especially attractive for skincare. It is non-irritating and non-sensitizing even in sensitive skin populations, and studies report no cytotoxicity in skin cells at the concentrations used in cosmetics (Hoppe et al., 1999). As an over-the-counter ingredient, CoQ10 is now included in many anti-aging creams and serums to help reduce wrinkles and photodamage. While topical CoQ10 works primarily at the skin surface and within the epidermis, these local effects complement systemic CoQ10 benefits – protecting the skin barrier and appearance, which are important aspects of overall healthy aging. In summary, peer-reviewed clinical evidence supports CoQ10’s role in improving skin firmness, reducing wrinkle depth, enhancing repair of photodamage, and boosting antioxidant capacity in the skin, making it a valuable component of both systemic and topical anti-aging strategies.