Abstract
The Japanese diet and the Mediterranean diet are rich in polyamines (spermidine and spermine). Increased polyamine intake elevated blood spermine levels, inhibited aging-associated pro-inflammatory status (increases in lymphocyte function-associated antigen-1 (LFA-1) on immune cells), suppressed aberrant gene methylation and extended the lifespan of mice. To test the effects of increased polyamine intake by humans, 30 healthy male volunteers were asked to eat polyamine-rich and ready-to-eat traditional Japanese food (natto) for 12 months. Natto with high polyamine content was used. Another 27 male volunteers were asked not to change their dietary pattern as a control group. The volunteers’ age of intervention and control groups ranged from 40 to 69 years (median 48.9 ± 7.9). Two subjects in the control group subsequently dropped out of the study. The estimated increases in spermidine and spermine intakes were 96.63 ± 47.70 and 22.00 ± 9.56 µmol per day in the intervention group, while no changes were observed in the control group. The mean blood spermine level in the intervention group gradually rose to 1.12 ± 0.29 times the pre-intervention level after 12 months, and were significantly higher (p = 0.019) than those in the control group. Blood spermidine did not increase in either group. LFA-1 on monocytes decreased gradually in the intervention group, and there was an inverse association between changes in spermine concentrations relative to spermidine and changes in LFA-1 levels. Contingency table analysis revealed that the odds ratio to decrease LFA-1 by increased polyamine intake was 3.927 (95% CI 1.116–13.715) (p = 0.032) when the effect of acute inflammation was excluded. The results in the study were similar to those of our animal experiments. Since methylation changes of the entire genome are associated with aging-associated pathologies and our previous studies showed that spermine-induced LFA-1 suppression was associated with the inhibition of aberrant gene methylation, the results suggest that dietary polyamine contributes to human health and longevity.
Highlights
Aging is associated with increased pro-inflammatory status, and the resultant persistent chronic inflammation is an underlying condition that is responsible for many aging-associated pathologies [1,2]
Analyses of the pre-intervention data showed that age was not significantly related to levels of blood spermine (SPM) with a negative r value (r = −0.150, p = 0.267) (SPM = 2.505 − 0.012 × age) (Figure 1a), blood spermidine (SPD) with a positive r value (r = 0.142, p = 0.295) (SPD = 3.419 + 0.025 × age) (Figure 1b), and the spermine to spermidine ratio (SPM/SPD) with a negative r value (r = −0.192, p = 0.154) (SPM/SPD = 0.660 − 0.0045 × age) (Figure 1c), while there was no statistical significance
Mono-CD11aMFIs had no correlation with SPD (r = −0.059, p = 0.662) (Figure 1f)
Summary
Aging is associated with increased pro-inflammatory status, and the resultant persistent chronic inflammation is an underlying condition that is responsible for many aging-associated pathologies [1,2]. Increased demethylation of gene promoter enhances transcription and increased methylation diminishes this process. Demethylation of genes involved in the progression of aging-associated pathologies and methylation of genes involved in the inhibition of aging-associated pathologies promotes these pathologies. Aberrant gene methylation is closely associated with both the progression of aging-associated pathologies and the lifespan of humans [5,6]. Nutritional components and macrobiotics in healthy diets have biological roles in inhibiting an aging-associated pro-inflammatory status, but the key nutritional components and dietary patterns and their effects on human health are still uncertain
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