Background/Objectives: this study evaluated the differential effects of two distinct dietary nucleotide supplements, combined with spontaneous physical activity, on neuromuscular, cognitive, and metabolic adaptations in older adults. Methods: Sixty-nine physically independent older adults (aged 60–75 years) were randomly assigned to three groups: (1) a yeast nucleotides formulation (YN) standardized in a high content of free nucleotides (>40%) rich in all macro and micro nutrients naturally occurring in yeast cell (amino acids, minerals and B-group vitamin); (2) a neuro-based formulation (NF) consisting of a blend of monophosphate nucleotides 5′; or (3) a placebo. Participants maintained their spontaneous physical activities without structured exercise during a 10-week intervention. Assessments included physical function, cognitive performance, body composition, quality of life, and serum biomarkers of oxidative stress, inflammation, and neurogenesis. Results: Both nucleotide-supplemented groups demonstrated significant improvements compared to placebo in physical performance (p ≤ 0.045), cognitive function (Trail Making Test B [TMT-B]: p ≤ 0.012), oxidative stress biomarkers (p ≤ 0.048), inflammatory cytokines (p ≤ 0.023), and quality-of-life parameters (p ≤ 0.047). Body composition remained stable in supplemented groups, whereas placebo increased fat mass (5.04%) and decreased muscle mass (−2.18%). Conclusions: Dietary nucleotide supplementation enhances the benefits of spontaneous physical activity across all measured variables in older adults, highlighting nucleotides as promising nutritional support for healthy aging. YN exhibited a trend toward greater inflammatory modulation, whereas NF showed a tendency toward enhanced neurotrophic effects and functional improvements, with a statistically significant improvement in the Timed Up and Go Test (p = 0.014). These findings underscore the potential for tailored nucleotide-based interventions to optimize distinct physiological domains in aging populations.

Background/Objectives: This study compared the effects of high-resistance training (RT) programs, with or without curcumin supplementation, on variables commonly associated with metabolic syndrome (MetS), including body composition, blood pressure, and metabolic parameters. Methods: Eighty-one older adults at risk of MetS (BMI > 25 kg/m², fat mass > 32%, and systolic blood pressure > 130 mmHg in half of the participants) were randomly assigned to six groups, which were comprised as follows: four experimental groups involving either accentuated eccentric or maximal strength RT with curcumin or placebo and two control groups receiving either curcumin or placebo. Experimental groups completed a 16-week full-body RT with elastic bands, while controls did not exercise. Results: The results showed that (I) all experimental protocols significantly reduced fat mass (p ≤ 0.001), with the maximal strength RT group supplemented with curcumin (Max-Cur) showing the greatest reduction, at 14.3%; (II) muscle gains were significant and comparable across experimental groups (p ≤ 0.008); (III) both systolic and diastolic blood pressure decreased similarly across experimental groups (p ≤ 0.001); (IV) metabolic parameters significantly improved across experimental groups (p ≤ 0.037), except for creatinine, which showed an undesirable peak only in the Max-Cur group; (V) curcumin supplementation enhanced the effects of both RT programs; and (VI) between 54% and 100% of participants achieved clinically meaningful improvements in seven out of ten MetS-related variables across experimental groups. Conclusions: Our findings indicate that high-RT programs combined with curcumin supplementation positively impacted all MetS-related variables. The Max-Cur RT group stood out as the most beneficial, with the greatest fat mass reductions, highlighting this approach as a promising strategy to reduce the risk of MetS in older adults.

To compare two 16-week high-load, velocity-intentional resistance training programs-elastic bands (HL-VIRT-EB) vs. water-based (HL-VIRT-AQ)-combined with creatine or placebo supplementation on neuroplasticity, oxidative stress, inflammation, strength, physical function, cognition, and quality of life in older adults. In a randomized controlled trial, 103 community-dwelling older adults (57 women, 46 men; 68.2 ± 4.6 y) were assigned to HL-VIRT-EB + Creatine, HL-VIRT-EB + Placebo, HL-VIRT-AQ + Creatine, HL-VIRT-AQ + Placebo, Control+Creatine, or Control+Placebo. Training was performed 3×/week (60 min). Creatine was consumed daily (3 g). Outcomes included brain-derived neurotrophic factor, F2-isoprostanes (F2-iso), glutathione peroxidase (GPx), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), isokinetic strength (knee/elbow, 60°·s^-1), handgrip, timed up-and-go, 30-s chair-stand, 6-min walk, trail-making test, and SF-36. ANCOVAs and correlations were conducted. Both training modalities produced significant improvements in neurocognitive biomarkers, oxidative/inflammatory profiles, strength, functional performance and quality of life (p < 0.05). HL-VIRT-AQ yielded greater reductions in F2-iso and TNF-α and larger gains in functional tests compared to HL-VIRT-EB (d = 0.12-1.18), which elicited superior upper-limb strength gains. Creatine provided additional benefits, increasing GPx, reducing IL-6/TNF-α and improving strength and function when combined with exercise modalities. Creatine alone reduced F2-iso and TNF-α and improved perceived health versus placebo. High-load, velocity-intentional resistance training-on land or in water-effectively improves neurocognition, oxidative balance, inflammation, strength, function, and quality of life in older adults. Aquatic training is particularly effective for attenuating oxidative stress and inflammation. Creatine supplementation confers complementary, modality-specific benefits and supports their use in combination to high-speed resistance exercise to promote healthy aging. NCT06620666 (ClinicalTrials.gov).