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Catching up with healthspan and lifespan supplements: A roundup of the latest science

Preclinical models support biological plausibility, while human studies more often showed selective or exploratory benefits.
Preclinical models support biological plausibility, while human studies more often showed selective or exploratory benefits. (Andrew_Brookes / Getty Images)

Research on supplementation and aging is advancing quickly, helping to supplant “live longer” language with more nuanced claims based on closer examination of biological mechanisms that might help people live better for longer if they test out in human clinical trials.

Across the latest studies, many driven by the companies developing and supplying the ingredients, the research is narrowing to focus on measurable endpoints including mobility and muscle strength, skin structure, menopause symptoms, vascular function, cognition, inflammatory proteins and metabolites related to NAD+.

Worm, mouse, cell and mechanistic studies featuring ingredients from longevity compounds to more traditional botanical extracts continue to pursue pathways and biomarkers tied to aging, including oxidative stress, inflammation, mitochondrial function, collagen and extracellular matrix remodeling, gut microbiome signaling and cellular senescence. Human trials tend to show more selective outcomes, with benefits often limited to specific populations, endpoints or exploratory analyses.

Multi-ingredient V14 vs. AG1 shows healthspan promise in worms

A study led by UK contract research organization Magnitude Biosciences and published in the Springer Nature journal Biogerontology examined the potential role of a multi-ingredient daily blend in supporting healthspan in a C. elegans roundworm model.

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The V14 Daily Reds Longevity Blend product used in the study and marketed by Youth&Earth (London, UK) is formulated with NMNH, spermidine, calcium AKG, trans resveratrol, taurine, glycine, pterostilbene, lithium microdose, quercetin dihydrate, carotenoids, ginger, magnesium malate, L-carnitine + 27 antioxidant, superfruit, mineral and vitamin ingredients.

The researchers compared V14 with daily greens powder AG1 and a DMSO control, using the automated WormGazer system to track movement as the worms aged. V14-treated worms maintained stronger mobility measures in later adulthood, including a higher fraction of moving animals and greater speed and distance traveled, while AG1 was associated with reduced movement relative to the control.

While V14 was linked to improved movement-based healthspan readouts, it did not consistently extend lifespan. RNA sequencing suggested the supplement may act through changes in genes related to lipid metabolism, detoxification, stress response and immunity.

The researchers noted that further work is needed to clarify dose effects, identify the contribution of individual ingredients and determine whether the results translate beyond worms.

Novel senolytic linked to exploratory changes in senescence-related protein biomarkers

Two days of supplementation with a novel multi-ingredient supplement was associated with exploratory changes in several blood-based markers linked to cellular senescence in a pilot decentralized, single-arm pilot trial published in the International Journal of Molecular Science.

The Qualia Senolytic product used in the study and marketed by Qualia Life Sciences (Carslbad, CA) is formulated with fisetin, Quercefit quercetin phytosome, Longvida curcumin extract, olive leaf extract, soybean seed isoflavones, luteolin, milk thistle silymarin, piperlongumine, and Senactiv (Panax notoginseng and Rosa roxburghii extracts).

The Qualia-led study recruited 69 healthy adults between the ages of 45 and 79 who consumed a two-day serving of 12 capsules and completed at-home fingerstick blood collection and quality-of-life questionnaires at baseline and day seven. The analysis focused on senescence-associated secretory phenotype, or SASP, biomarkers measured with the Olink Target 48 Cytokine panel, including primary outcomes TNF, IL-1β, CXCL8 and VEGFA.

The study found no significant changes in the pre-specified primary protein outcomes after correction for multiple comparisons, but exploratory unadjusted analyses showed reductions in several chemokines associated with senescence and inflammation. Participants also reported improvements in several quality-of-life measures, and no safety concerns were identified.

As limitation, the cited lack of placebo group and the short duration of the trials, adding the study did not directly measure senescent cell burden.

Haleon study reports MVM supplements benefit specific groups

Multivitamin and mineral supplements showed selective benefits for some cognitive, psychological, cardiovascular and pregnancy-related outcomes, but did not consistently improve mortality or broad disease-risk measures in a rapid review of meta-analyses.

Writing in Ageing Research Review, researchers funded by Haleon and the University of Singapore reviewed 19 meta-analyses published from 2000 to 2025, covering more than 5.5 million participants and evidence from randomized controlled trials, cohort studies and case-control studies across cardiovascular, cognitive, psychological, immune, cancer, eye, musculoskeletal, pregnancy and pediatric outcomes.

Randomized trials found signals for improved global cognition, episodic memory, immediate recall, psychological symptoms and systolic blood pressure in certain populations, but no clear benefit for all-cause mortality, COVID-19 outcomes or several cognitive domains. Observational studies linked multivitamin and mineral use to lower risks of colorectal cancer, coronary heart disease, cataracts and fragility hip fractures, though findings were inconsistent and did not extend to breast cancer, prostate cancer, stroke or overall mortality.

During pregnancy, supplementation was associated with lower risks of small-for-gestational-age births, neural tube defects and some pediatric cancers, but not preterm birth, stillbirth or low birth weight.

The researchers noted that the results suggest a more targeted use of supplementation rather than broad recommendations for healthy aging and longevity and that that inconsistent supplement definitions, heterogeneous formulations and limited information on baseline nutritional status make it difficult to determine who is most likely to benefit.


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Avea Life’s Colgevity studied across worms, mice and humans

A collagen-derived amino acid blend from longevity supplement brand Avea Life (Zug, CH) reduced biological age and improved skin measures in an observational human study, while also extending healthspan and lifespan in preclinical models, a team of Swiss researchers reported in npj Aging.

The work, funded by Avea Life, focused on Colgevity a 3:1:1 ratio of glycine, proline and hydroxyproline, three amino acids abundant in collagen, testing the ratio in C. elegans, human dermal fibroblasts, aged mice and a single-arm human supplementation study.

In worms, the amino acid combination prolonged collagen-related gene expression during aging and increased lifespan by 6% to 27% across several trials. In human skin cells, RNA sequencing showed increased expression of collagen and extracellular matrix-related genes, while aged mice given the blend for six months maintained grip strength and accumulated less visceral fat than controls.

The human observational study used the Collagen Activator-branded formulation containing the amino acid blend, calcium alpha-ketoglutarate, astaxanthin and vitamin C. Participants showed improvements in skin texture, hydration and elasticity within three months, and the subgroup completing saliva-based biological age testing showed an average 1.37-year reduction after six months.


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Review considers NAD⁺ supplementation for anti-aging and wellness

A review conducted by medical spa Allure Management (King of Prussia, PA) and an independent research consultant in Ondo, Nigeria assessed 113 peer-reviewed intervention studies published between January 2010 and October 2025, including 33 human studies and 80 rodent studies evaluating NAD+-related compounds such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinamide and niacin.

Finding published in Ageing Research Reviews, found that in human trials, oral NR and NMN were generally well tolerated and consistently showed biochemical target engagement, with increases in circulating or cellular NAD-related metabolites. Effects on metabolic, vascular and physical-performance outcomes, however, were heterogeneous, often null or limited to specific endpoints or populations.

Rodent studies more often reported improvements in metabolic, mitochondrial, inflammatory and functional outcomes, supporting biological plausibility for NAD+ augmentation in aging biology.

The researchers also noted that animal findings did not translate consistently into clinically meaningful effects in human studies and called for larger, longer randomized trials with standardized, clinically meaningful endpoints to determine whether NAD+ augmentation can produce measurable healthspan benefits.

Some supplements may support vascular function

A review published in Journal of Clinical Medicine found that some nutritional supplements may modestly support vascular function, though evidence for reducing cardiovascular events remains limited.

Researchers from the National and Kapodistrian University of Athens and Attikon University Hospital in Greece reviewed evidence on supplements targeting nitric oxide biology (L-arginine/L-citrulline and citrulline derived from watermelon), polyphenol-rich foods and extracts (cocoa flavan-3-ols and grape polyphenols), mitochondrial redox balance (CoQ10 and the mitochondria-targeted antioxidant MitoQ), endothelial glycocalyx-supporting formulations, olive-derived bioactive compounds, curcumin and S-allyl cysteine.

Reported benefits were mainly seen in surrogate outcomes such as flow-mediated dilation, pulse wave velocity, blood pressure, endothelial glycocalyx integrity and oxidative stress markers, with more consistent signals for polyphenol-rich supplements, CoQ10, MitoQ, L-citrulline and selected olive-derived compounds.

The researchers said these effects may involve improved nitric oxide bioavailability, lower oxidative stress and inflammation, mitochondrial redox balance and endothelial glycocalyx preservation.

Entrenching ergothioneine as longevity vitamin

Emerging research continues to position ergothioneine—which up until recently was a fairly obscure dietary compound—as a longevity vitamin, one that is not required for short-term survival but perhaps essential for long-term health.

A science review led by ergothioneine supplier Blue California explored the existing body of observational, interventional and mechanistic studies, reporting that ergothioneine does indeed meet the proposed criteria for this classification.

According to the review, low blood ergothioneine levels are consistently associated with higher risk of cognitive impairment, neurodegenerative disease, cardiovascular disorders, frailty and mortality. Early intervention studies suggest supplementation may support cognition, memory and sleep quality at doses up to 25 mg/day, while mechanistic research points to antioxidant, anti-inflammatory, mitochondrial and NAD⁺-related pathways, with potential relevance across brain, cardiovascular, metabolic, immune and other aging-related systems.

For this work, Blue California collaborated with independent researchers from the National University of Singapore, Flinders University and CSIRO, Australia’s national science organization.


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Is blood NAD+ a dead end in aging research?

An investigation into one of aging research’s most prominent molecules has reported that NAD+, a compound central to cellular metabolism, may not decline in human blood the way many in the aging and longevity community once thought.

Published in Nature Metabolism, the study found that whole-blood NAD+ levels remained stable across multiple age groups and lifestyle interventions, challenging the idea that a blood test could use the molecule as a reliable marker of aging.

The study used a rigorously validated assay to analyze whole-blood samples from more than 300 people across independent cohorts that included younger and older adults, elite athletes, frail older adults undergoing diet or exercise interventions, and participants receiving supplemental nicotinamide riboside—a form of vitamin B3—to boost NAD+.

Across the cohorts, the researchers observed no meaningful link between whole-blood NAD+ and age, nor did they report any major shifts after lifestyle interventions including exercise and protein-rich diets. They did however note an expected rise in blood NAD+ in the supplementation group.

Importantly, the study highlighted that discrepancies in laboratory handling as much as biology may also influence inconsistencies in the scientific literature.


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Study explores Sepibright strawberry leaf extract for memory

A study published in The Journal of Nutrition, Health and Aging found that strawberry leaf extract supplementation was associated with exploratory improvements in episodic memory and perceived stress among older adults with self-reported memory complaints.

The team of French researchers assigned 109 adults between the ages of 60 and 80 to receive either 300 mg/day of strawberry leaf extract (Sepibright, Seppic, France) or placebo for 12 weeks. Cognitive performance was assessed with CANTAB tests of memory and executive function, while perceived stress, sleep quality, fatigue and self-reported memory complaints were measured with validated questionnaires.

The primary mixed-effects analysis did not show significant treatment-by-time interactions, but exploratory analyses found greater improvements with strawberry leaf extract than placebo on Paired Associates Learning total errors at weeks six and 12, along with a greater reduction in perceived stress at week six. Within-group improvements were also reported for verbal memory and some working-memory measures in the supplement group.

The study was funded by French cosmetics, health and pharma ingredient supplier Seppic (La Garenne-Colombes, France), a subsidiary of Air Liquide Healthcare.

Probiotic found to boost worm lifespan by almost 20%

A probiotic strain isolated from a healthy centenarian was associated with longer lifespan, improved movement and reduced fat accumulation in a worm model of aging.

Writing in Frontiers in Nutrition, researchers from Chinese biotech company AIage Longevity Science Corporation (Shenzhen, PRC) and Guangxi Key Laboratory of Longevity Science and Technology evaluated the effects of Limosilactobacillus reuteri A21041 using a C. elegans model. Lifespan assays, lipid storage experiments, motility tests and stress resistance assays were used to compare worms fed A21041 with those fed a standard Escherichia coli OP50 control. The probiotic was found to extend the lifespan of C. elegans by 19.3% and reduce fat accumulation by up to 70%.

Mechanistic analyses suggested that the effects may involve insulin/IGF-1 signaling, AMPK-related pathways, lysosome signaling, fatty acid degradation and antioxidant responses, including increased SOD activity and upregulation of stress-related genes such as gst-4, hsp-16.2, atf-4 and cth-2.


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Probiotics show promise for preserving muscle health

Probiotic use was linked with better muscle-related measures and lower sarcopenia prevalence in older adults, while cell and computational analyses pointed to possible gut–muscle axis mechanisms in a study published in Frontiers in Cellular and Infection Microbiology.

Using data from NHANES, UK Biobank and GMrepo, researchers from The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University in China examined associations between probiotic exposure, microbiome diversity, inflammation and muscle outcomes in older adults. Probiotic users showed higher handgrip strength, greater fat-free mass, lower inflammatory burden and lower prevalence of confirmed sarcopenia than non-users across the analyzed cohorts.

In cell experiments, probiotic-conditioned media increased myotube fusion, diameter and expression of myogenic markers, while reducing NF-κB and TNF-α and increasing PGC-1α. Molecular docking suggested that short-chain fatty acids, particularly butyrate, may interact with proteins involved in anabolic, metabolic and inflammatory signaling, including mTOR, AMPK and NF-κB.

While observational, the study also used machine learning models to predict sarcopenia risk, with XGBoost outperforming Random Forest and highlighting handgrip strength, protein intake, CRP, microbiome diversity and probiotic exposure as key features.


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NR may improve muscle-specific marker of biological aging

Supplementation with nicotinamide riboside may reduce muscle epigenetic age acceleration measured by the Muscle Epigenetic Age Test (MEAT) clock, according to an analysis of data from past clinical studies.

Published in Aging Cell and using seven epigenetic clocks, the analysis included results from a five-month human NR trial (using 1,000 mg per day of Niagen nicotinamide riboside from Niagen Bioscience (Los Angeles, CA) and independent four-to-six-week high-intensity interval training (HIIT) studies, along with new in vitro data from human muscle cells. Both interventions have been proposed to improve aging-related mitochondrial decline.

Findings suggested that changes in muscle mitochondrial DNA content correlated with changes in MEAT-derived epigenetic age acceleration, which suggested a potential relationship between mitochondrial adaptations and epigenetic clock measures. Effects appear to be both clock- and intervention-specific, with divergent patterns potentially reflecting differences in biological pathways, intervention timing or short-term muscle remodeling responses rather than straightforward acceleration or slowing of aging.

Acknowledging limitations with the mechanistic data, the researchers noted that the study provides evidence to support research aimed at disentangling the molecular mechanisms underlying fluctuations in human biological aging in response to mitochondria targeting interventions.


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Femal Osteo pollen extract combo may improve menopause symptoms and bone health

A non-hormonal supplement combining purified cytoplasm of pollen with vitamins D3 and K2 was linked to improvements in menopausal quality-of-life measures and bone-turnover markers in a small retrospective study published in Nutrients.

The study, funded by Shionogi SRL, the Italian operating subsidiary of Japanese company Shionogi & Co., investigated the effect of Femal Osteo, a Shionogi supplement containing 320 mg of PCP, 25 mcg of vitamin D3, 10 mg of vitamin E, 180 mcg of vitamin K2 and 1.4 mg of vitamin B6.

Researchers from Italian clinical and academic centers evaluated 45 symptomatic pre- and postmenopausal women treated for three months with Femal Osteo or followed as untreated controls. Outcomes included Menopause-Specific Quality of Life questionnaire domains, serum vitamin D, calcium–phosphorus–PTH balance, bone-turnover markers and bone-density-related measures.

Findings indicated that the combination may help manage hot flashes and mood-related menopausal symptoms while supporting bone metabolism, but noted that the study requires confirmation in larger placebo-controlled randomized trials.


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Combination-strain probiotic may ease menopause symptoms, improve quality of life

A three-strain probiotic formula from AB Biotics and Kaneka Probiotics could help attenuate menopause symptom and improve quality of life in perimenopausal and postmenopausal women.

Published in The Journal of The Menopause Society, the randomized, double-blind, placebo-controlled trial conducted by researchers from AB-Biotics, Trialance, Universitat Internacional de Catalunya and Menoclínica Palacios assigned 245 women between the ages of 45 and 60 to receive either the probiotic formula or placebo for three months. The formula contains Levilactobacillus brevis KABP052, Lactiplantibacillus plantarum KABP051 and Pediococcus acidilactici KABP021 at 1 × 109 CFU/day.

The researcher team reported that the probiotic group had a greater reduction in total Menopause Rating Scale II scores than placebo, with improvements driven mainly by the somato-vegetative domain (e.g., sleep disturbances and heart discomfort) and, in per-protocol analysis, the psychological domain. Utian Quality of Life scores also improved more with the probiotic, while total Cervantes Quality of Life scores did not differ significantly between groups.


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Do functional ingredients affect healthy skin aging through the gut–brain–skin axis?

Functional ingredients may support skin aging through a wider biological network connecting the gut, brain and skin, rather than through direct effects on skin tissue alone.

Writing in International Journal of Molecular Sciences, researchers from Korea University reviewed evidence on the gut–brain–skin axis, focusing on how food-derived bioactives such as polyphenols, probiotics, omega-3 fatty acids, peptides and amino acid-derived metabolites may influence skin health, cognitive function and aging-related inflammation.

The review found that many of these ingredients appear to converge on shared mechanisms, including modulation of gut microbiota, improved intestinal and skin barrier function, immune regulation, reduced oxidative stress and effects on neuroendocrine signaling through pathways such as the HPA axis.

Polyphenols such as quercetin, EGCG and resveratrol were highlighted for antioxidant and anti-inflammatory effects, while probiotics and omega-3 fatty acids were linked to microbial, immune and lipid-mediator pathways that may affect inflammatory skin outcomes and barrier integrity.

Much of the evidence was identified as preclinical or focused on isolated gut, brain or skin endpoints, with the researchers calling for studies that integrate clinical designs that combine microbiome profiling, metabolomics, neuroendocrine and immune markers, skin imaging and validated dermatological endpoints to determine whether targeting the gut–brain–skin axis can produce meaningful benefits for healthy skin aging.

Kimchi probiotic shown to slow age-related muscle loss in mice

Kimchi-derived probiotic Weissella cibaria Wikim0187 was linked to improvements in muscle mass and strength in aged mice in a study published in Journal of Microbiology and Biotechnology.

Researchers from the World Institute of Kimchi, the Korean Culture Center of Microorganisms, Chonnam National University, the Korea Institute of Radiological and Medical Sciences, Korea University and Pharmsville Co. tested the probiotic in older male mice given daily oral supplementation for four months, along with cell experiments using C2C12 myoblasts.

The study found that Wikim0187 increased gastrocnemius and quadriceps muscle mass, improved absolute and body-weight-adjusted grip strength, and increased muscle fiber cross-sectional area. In cell experiments, the probiotic also helped protect myoblasts from oxidative stress-related damage.

Mechanistic analyses suggested that the probiotic may act through several pathways, including reduced expression of muscle atrophy-related markers MuRF-1 and Atrogin-1, increased expression of myogenic markers MyoD and Myogenin, higher Akt phosphorylation and remodeling of the gut microbiota, including enrichment of taxa such as Akkermansia and Bifidobacterium.

Study evaluates effects of prunes on bone health in older men

One year of prune supplementation did not significantly improve total or lumbar spine bone mineral density in older men with low or declining bone mass, according to a randomized controlled trial published in Nutrients.

U.S. university researchers supported by a USDA-NIFA grant assigned 59 men between the ages of 55 and 80 to consume 100 grams of prunes, 50 grams of prunes or no prunes daily for 12 months. All groups also received calcium and vitamin D, and bone density and blood biomarkers were measured at baseline, three, six and 12 months.

The study found no significant changes in total bone mineral density, lumbar spine bone mineral density or DXA T-scores across the prune and control groups. C-reactive protein also did not change significantly over time.

Some exploratory differences were observed in bone-turnover biomarkers. Osteoprotegerin declined less in both prune groups than in the control group, while TRAP5b increased more in the control group than in the 100-gram prune group. However, these biomarker differences did not correspond to detectable improvements in bone density.

The researchers noted that the findings are limited by the smaller-than-planned sample size, lack of a true placebo group and variation in baseline bone status, and said larger studies are needed to clarify whether prunes affect bone metabolism in men.

What the latest science suggests

  • Healthspan evidence is strongest at the function or biomarker level. Across ingredients, studies most often tracked mobility, muscle strength, skin measures, cognitive scores, vascular markers, bone-turnover biomarkers, NAD-related metabolites, inflammatory proteins and menopause quality-of-life scores in lieu of hard longevity outcomes.
  • Preclinical models support biological plausibility, but human translation is uneven. Worm and mouse studies reported effects on lifespan, movement, muscle preservation, fat accumulation, stress response and collagen-related pathways, while human studies more often showed selective or exploratory benefits.
  • Supplement effects are endpoint-specific. NAD⁺ precursors, probiotics, collagen-related amino acids, ergothioneine, polyphenols, pollen extract and prunes were associated with a variety of outcomes that potentially contribute to healthy aging rather than a single broad “anti-aging” effect.
  • Study design limits interpretation. Small samples, short durations, observational designs, single-arm trials, heterogeneous formulations and reliance on surrogate endpoints make many claims suggestive rather than definitive.