Aging is a natural process characterized by a progressive decline in physiological functions, leading to multiple alterations across the body and varying between individuals [1].

To account for these differences, the concept of biological age (BA) has been proposed as a useful measure of health status [2]. Evidence suggests that BA, rather than chronological age (CA), better predicts disease risk and mortality [3]. BA can be estimated using different approaches, including DNA methylation, telomere length, blood-based measures, or composite indices derived from clinical biomarkers [4–6]. The difference between BA and CA, termed Δage, indicates whether an individual is aging faster or slower than expected; a positive Δage reflects accelerated aging, whereas a negative Δage suggests slower, potentially healthier aging [3].

Lifestyle and environmental factors, such as smoking [7] and obesity [8], are linked to faster BA, while adherence to healthy dietary patterns, including the Mediterranean Diet (MD), and consumption of polyphenol-rich foods have been associated with slower biological aging [9, 10].

Among lifestyle factors that may modulate BA, moderate wine consumption, particularly in the context of a traditional MD, represents a potentially beneficial behavior, due to its reported cardiovascular benefits [3, 11].

Although excessive alcohol consumption is a well-established risk factor for various chronic diseases [12], regular and moderate wine intake during meals is a hallmark of the traditional MD [13, 14] and has been associated with improved cardiovascular outcomes and longevity [15, 16]. An inverse association of biological aging with alcohol consumption has already been reported in previous findings from the same Moli-sani cohort where moderate alcohol consumption showed a deceleration of biological aging [3].

While the concept of “moderate consumption” varies across contexts, the traditional MD typically involves higher, but still moderate, ethanol intake, mainly in the form of red wine during main meals, compared to many national drinking guidelines in Europe [13]. Yet, some other organizations, as the World Health Organization, have stated that no level of alcohol consumption can be considered safe [17]. The potential mechanisms by which moderate wine intake may confer health benefits, particularly improved cardiovascular outcomes, include the anti-inflammatory and antioxidant effects of bioactive compounds such as resveratrol [18], favorable modulation of lipid profiles, particularly HDL cholesterol [19], enhanced endothelial function [20], reduced platelet aggregation [21], and improved insulin sensitivity [22]. These effects may be reflected in circulating biomarkers related to inflammation, lipid metabolism, and vascular function, processes whose collective patterns are synthetically captured by biological age measures [23], potentially representing pathways through which moderate wine consumption contributes to longevity and reduced disease risk.

To date, no study has directly investigated the association between wine consumption and biological aging based on circulating biomarkers, whereas previous research has primarily focused on ethanol intake in the context of at-risk or heavy drinking patterns [24–26].

To address this knowledge gap, we investigated the relationship between patterns of wine consumption within the context of a traditional MD and biomarkers-based biological aging in a well-established population cohort in Southern Italy.

The sample under study consisted of 22,495 participants (47.9% males) with a mean CA of 55.6 years (SD ± 11.7 years), while BA was 54.9 years (SD ± 9.1 years), and Δage −0.7 years (SD ± 7.7 years). The proportions of abstainers, former drinkers, moderate drinkers, Mediterranean moderate drinkers, and heavy drinkers were 30.4%, 3.3%, 44.7%, 15.7%, and 5.9, respectively (Table 1).

CA differed between groups, with Mediterranean moderate and heavy drinkers being older than abstainers and moderate drinkers. BA showed smaller differences, with Mediterranean moderate drinkers having a slightly lower BA. Biological aging was lowest among Mediterranean moderate drinkers (Table 1).

Abstainers and former drinkers included a higher proportion of males (77.5% and 68.0%, respectively) compared to Mediterranean moderate (31.0%) and heavy drinkers (27.9%). Education levels and housing tenure also varied among groups, with heavy drinkers having a higher prevalence of lower education attainment. Multiple property ownership was lower among both heavy drinkers and abstainers compared with the other drinking categories. Mediterranean moderate and heavy drinkers reported higher energy intake, leisure-time physical activity, a greater percentage of former smokers, and lower BMI. Chronic conditions such as diabetes, hypertension, hyperlipidemia, CVD, and cancer showed variation across groups (Table 1).

In multivariable-adjusted regression analyses controlling for known risk factors and using abstainers as the reference category, Mediterranean moderate drinkers showed a small difference toward a slower increase in Δage (β = −0.22 years; 95% CI: −0.47 to 0.03) Heavy drinking showed a similarly small difference in the opposite direction (β = 0.20 years; 95% CI: −0.16–0.56), with wide confidence intervals for both estimates, spanning from a modest change to little or no difference.

Men classified as Mediterranean moderate wine drinkers had lower Δage compared to abstainers (β = −0.39; 95%CI: −0.78 to −0.01), whereas no differences in Δage were observed across wine consumption patterns in women. However, the formal test for interaction did not support sex-specific differences (p for interaction = 0.21); as an omnibus test across categories, it may have limited sensitivity to detect differences confined to a single category (Table 2).

These associations were also explored in dose-response analyses, which suggested a non-linear, J-shaped relationship between wine consumption (mL/d) and Δage in the overall sample (Figure 1A), with a weak overall association, the lowest estimates at moderate intakes, and wide uncertainty bands, consistent with the category-based results.

In sex-stratified analyses, a J-shaped association was observed in men (Figure 1B), whereas the relationship was virtually null in women (Figure 1C). In men, the nadir was identified at 172 mL/d (difference = −0.34; 95% CI: −0.66 to – 0.03), with protective effects extending up to 240 mL/day (difference = −0.31; 95% CI: −0.62 to −0.00046).

The association between Mediterranean moderate wine consumption and Δage did not differ across levels of adherence to the MD (β in the low MD adherence group: = −0.25; 95% CI: −0.53 to 0.02 vs. abstainers; and β in the high MD adherence group: = −0.08; 95% CI: −0.69 to 0.54 vs. abstainers), and this was confirmed also by a formal test of interaction (p-value for interaction = 0.82) (Table 3).

Age-stratified analyses showed no difference in the association between wine consumption and Δage among participants aged 35–54 years (Supplementary Figure S2a) and in elderly participants (Supplementary Figure S2c). In middle-aged individuals (Supplementary Figure S2b), a modest inverse association was observed at moderate intake (∼100–150 mL/day), though confidence intervals widened at higher consumption and non-linear trends were borderline, indicating a weak and uncertain effect.

Results from analyses conducted in a healthy sample free from major health conditions were consistent with those observed in the whole study sample (Supplementary Figure S3a).

A J-shaped association was observed among healthy men (Supplementary Figure S3b), similar to that seen in the general male population, whereas no association was found in healthy women (Supplementary Figure S3c).

Regarding ethanol consumption, none of the drinking patterns were associated with Δage overall or by sex, although an upward trend was observed in men classified as heavy drinkers compared to abstainers (β = 0.46 years; 95% CI: −0.06–0.98) (Supplementary Table S1). Dose-response analyses indicated that low to moderate ethanol intakes (0–30 g/day) were linked to either slight decreases or negligible changes in Δage, suggesting little effect on biological aging. In contrast, higher intakes (>30 g/day) showed a progressively positive association, with β estimates pointing to accelerated biological aging at levels above 60 g/day (Figure 2A). Similar patterns were observed in men (Figure 2B) but not in women (Figure 2C).

Analyses using MDS and its individual components showed that the MDS, consumption of vegetables, the monounsaturated-to-saturated fat ratio, and meat consumption were inversely associated with Δage in a dose-response manner, with evidence of a non-linear relationship (p-values for non-linearity <0.050) (Supplementary Figure S4, 5B, 6B, 6C). In contrast, consumption of fruits, cereals, legumes, fish, and dairy were not associated with Δage (Supplementary Figures S5, S6).

Our findings from a large population-based cohort in Southern Italy indicate that moderate wine consumption, as defined by a traditional MD, is associated with slower biological aging in men. A dose-response relationship was also observed, suggesting that moderate intake, consistent with a traditional MD, may positively influence aging trajectories. On average, men consuming about 200 mL of wine per day (roughly 1.5–2 glasses) were approximately 0.4 years biologically younger than non-drinkers.

The J-shaped relationship observed in men is consistent with prior work reporting a similar pattern between cardiovascular mortality and alcohol intake [39], suggesting that even low doses of alcohol may have protective effects that do not diminish at higher intakes.

Sex related differences in alcohol’s health effects may explained by i.e., variations in metabolism and hormones [40]. Women generally have lower alcohol dehydrogenase levels, resulting in greater alcohol absorption and stronger effects at lower doses. Hormonal factors may also contribute, though evidence from human studies on estrogen-related influences is inconsistent [41].

In our study, the inverse association between wine intake and biological aging appeared stronger in middle-aged participants. This may reflect age-related declines in liver function and alcohol-metabolizing enzymes, which slow alcohol processing and can increase related health risks [42].

Our analysis on the MDS and its individual components revealed that the J-shaped association was not limited to wine consumption, but also extended to other MD components, such as vegetables and the ratio of monounsaturated to saturated fats. These findings support our main analysis on wine, suggesting that wine is not the only dietary component showing this type of J-shaped association with biological aging. The counterintuitive results for meat consumption could reflect a protective role of animal proteins, particularly in preserving muscle mass and function during aging [43], as well as providing essential micronutrients such as vitamin B12, iron, and zinc, which are critical for healthy aging [44].

To date, previous studies have primarily focused on total ethanol intake, often in the context of heavy drinking or alcohol use disorders, and apparently no research has specifically examined Mediterranean populations [24–26].

Large scale studies using UK Biobank and Generation Scotland data found no evidence of an effect of alcohol consumption on accelerated biological aging, as assessed by measures of brain and epigenetic aging [45]. A Mendelian randomization study in the UK Biobank suggested that alcohol intake may shorten telomeres, but observational analyses showed this only for high consumption (≥17–29 units/week, about two and a half to four glasses per day), not for moderate drinking [24]. Also, in these analyses, overall diet quality was not included as an adjustment factor, thereby overlooking drinking habits in the context of the whole diet.

The Framingham Heart Study found that alcohol consumption, especially at higher levels and from liquor, was linked to faster epigenetic aging in mid-to-late adulthood. Alcohol was treated as a continuous exposure, with hazard ratios reported per unit increase in consumption, and drinking patterns considered only at-risk or heavy drinkers, while moderate consumption categories were not included [25].

In the Coronary Artery Risk Development in Young Adults Study, cumulative liquor and total alcohol consumption, as well as recent binge drinking, were associated with increased GrimAge acceleration, a second-generation marker of epigenetic age. Interestingly, beer showed only marginal associations, whereas wine showed no association with accelerated aging [26].

It is worth noting that all these studies analyzed alcohol consumption without distinguishing moderate intake thresholds-levels typically linked to cardiovascular benefits, and only one considered wine specifically as the exposure [25]. This distinction may be critical, as patterns of alcohol consumption, including beverage type, frequency and consumption with food, may have different associations with human health [46].

There are several potential mechanisms that can explain our findings. Wine is a major source of polyphenols which have been implicated in reducing inflammation, oxidative stress, and improving metabolic function, all mechanisms involved in aging, and specifically reflected in our biological age measure [13].

It is worth noting that, in our analyses, ethanol intake was not associated with slower biological aging, which points to non-ethanol components (e.g., polyphenols) as a more plausible explanation for the associations observed with wine, in line with previous evidence observed in the Moli-sani cohort [10]. Additionally, previous studies have shown that the protective associations of alcohol with certain health outcomes are more pronounced among wine drinkers, suggesting that these benefits may stem from components other than ethanol [16].

Finally, it is worth mentioning that previous cohort studies examining the association between alcohol consumption and various markers of biological aging have been conducted in non-Mediterranean populations. Importantly, alcohol metabolism is known to vary considerably across ethnic groups due to genetic differences in enzymes such as alcohol dehydrogenase and aldehyde dehydrogenase [47], which may influence drinking habits [48], as well as the physiological effects of alcohol and its relationship with aging-related outcomes [49].

Notably, in our study, the association between wine consumption and biological aging was similar across levels of MD adherence, potentially reflecting wine-specific components or consumption patterns rather than a broader dietary effect.