Nutrition and Healthy Ageing in Asia: A Systematic Review

Background: Nutrition plays a key role in modulating the likelihood of healthy ageing. In the present study, we aimed to conduct a systematic review to assess the impact of nutrition on healthy ageing in Asia. Methods: The systematic review was registered in the International Prospective Register of Systematic Reviews database (CRD42023408936) and conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Web of Science, and Embase databases were searched up to February 2023 without language restrictions. We included prospective cohort studies that evaluated the associations of intake of a single food or consumption of a single nutrient at midlife; adherence to various dietary patterns at midlife; and improved adherence to dietary patterns from mid- to late life with the likelihood of healthy ageing and its components. Results: Out of 16,373 records, we included 71 papers comprising 24 cohorts from Singapore, China, Japan, and Thailand. The healthy ageing components included cognitive function, physical function, and depression. The majority of studies supported the observation that the likelihood of healthy ageing and its components in late life was positively increased by a higher consumption of healthy foods, such as vegetables, fruits, fish, nuts, legumes, tea, milk, and dairy, at midlife, and also by greater adherence to dietary patterns with high diversity scores or high total antioxidant capacities. Furthermore, improved adherence to healthy dietary patterns from mid- to late life also increased the likelihood of healthy ageing in late life. Conclusion: Consuming healthy foods and adhering to healthy dietary patterns at midlife can promote the likelihood of healthy ageing. Moreover, improving diet quality from mid- to late life can still be beneficial.


Introduction
An increase in life expectancy and a decline in fertility rates have resulted in accelerated ageing of the population in many countries, including those in Asia. By 2050, a quarter of Asia's population is predicted to be ≥60 years old, which will inevitably lead to an increased number of older adults with chronic diseases and disability, and with profound consequences for health, health systems, the workforce, and budgeting for many Asian countries [1]. To provide a public health framework for action, World Health Organization has released the "World report on ageing and health", which calls for comprehensive public health action to promote healthy ageing, the latter being defined as developing and maintaining the functional ability that enables well-being in older age [2].
Nutrition and diet have been established as possessing some of the most important influences on health and ageing, with the overwhelming majority of evidence coming The quality of the included studies, as assessed using the Newcastle-Ottawa Scale, was considered to be high for all 71 studies (Table S2). The characteristics of the eligible studies are shown in Table 1. Sixteen cohorts were from China, five from Japan, two from Singapore, and one from Thailand. Most of the studies were conducted among middleaged or older participants, ranging in age from 40 to 89.2 years. The sample size ranged between 427 and 41,447, and the follow-up period ranged between 1.4 and 25.0 years. Food frequency questionnaires (FFQs) were used for data collection in most cohorts, except for the China Health and Nutrition Survey (CHNS), the Singapore Longitudinal Aging Studies, the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA), and the Zhejiang Ageing and Health Cohort Study. In these studies, 24 h dietary recalls for 3 consecutive days [7], 3-day dietary records [8][9][10], or simple food consumption questions [11][12][13] were used. The quality of the included studies, as assessed using the Newcastle-Ottawa Scale, was considered to be high for all 71 studies (Table S2). The characteristics of the eligible studies are shown in Table 1. Sixteen cohorts were from China, five from Japan, two from Singapore, and one from Thailand. Most of the studies were conducted among middleaged or older participants, ranging in age from 40 to 89.2 years. The sample size ranged between 427 and 41,447, and the follow-up period ranged between 1.4 and 25.0 years. Food frequency questionnaires (FFQs) were used for data collection in most cohorts, except for the China Health and Nutrition Survey (CHNS), the Singapore Longitudinal Aging Studies, the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA), and the Zhejiang Ageing and Health Cohort Study. In these studies, 24 h dietary recalls for 3 consecutive days [7], 3-day dietary records [8][9][10], or simple food consumption questions [11][12][13] were used.

Association between Nutrition and Healthy Ageing
Three studies [7,14,15], which included 17,244 participants in two cohorts, investigated the multidimensional concept of healthy ageing. In the SCHS, healthy ageing was defined as the absence of specific chronic diseases; good mental and overall self-perceived health; good physical functioning; and a lack of adverse outcomes of cognitive impairment, limitations in instrumental activities of daily living (IADL), or function-limiting pain [14,15]. Data from the SCHS reported that a greater adherence to various healthy dietary patterns at midlife, defined by the alternate Mediterranean diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) diet, the Alternative Healthy Eating Index (AHEI)-2010, the overall plant-based diet index (PDI), and the healthful plant-based diet index (hPDI), was associated with a higher likelihood of healthy ageing in late life, with the odds ratio (OR) comparing the highest with the lowest quartile of diet quality scores ranging from 34% to 53% for healthy ageing [14]. Furthermore, consistent or improved adherence to the DASH diet from mid-to late life was associated with a 19% to 108% higher likelihood of healthy ageing [15]. In the CHNS, a healthy ageing score was calculated by adding up the standardized scores for physical functional limitation, comorbidity, cognitive function, and psychological stress, with a lower score indicating a healthier ageing process [7]. Data from the CHNS revealed that a higher level of dietary diversity was associated with a lower score, representing healthier ageing (T3 vs. T1: β, −0.16; 95% confidence interval [CI], −0.20 to −0.11) [7]. A summary of the associations between diet/nutrition and the outcomes of ageing is presented in Figure 2.

Association between Nutrition and Healthy Ageing
Three studies [7,14,15], which included 17,244 participants in two cohorts, investigated the multidimensional concept of healthy ageing. In the SCHS, healthy ageing was defined as the absence of specific chronic diseases; good mental and overall self-perceived health; good physical functioning; and a lack of adverse outcomes of cognitive impairment, limitations in instrumental activities of daily living (IADL), or function-limiting pain [14,15]. Data from the SCHS reported that a greater adherence to various healthy dietary patterns at midlife, defined by the alternate Mediterranean diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) diet, the Alternative Healthy Eating Index (AHEI)-2010, the overall plant-based diet index (PDI), and the healthful plant-based diet index (hPDI), was associated with a higher likelihood of healthy ageing in late life, with the odds ratio (OR) comparing the highest with the lowest quartile of diet quality scores ranging from 34% to 53% for healthy ageing [14]. Furthermore, consistent or improved adherence to the DASH diet from mid-to late life was associated with a 19% to 108% higher likelihood of healthy ageing [15]. In the CHNS, a healthy ageing score was calculated by adding up the standardized scores for physical functional limitation, comorbidity, cognitive function, and psychological stress, with a lower score indicating a healthier ageing process [7]. Data from the CHNS revealed that a higher level of dietary diversity was associated with a lower score, representing healthier ageing (T3 vs. T1: β, −0.16; 95% confidence interval [CI], −0.20 to −0.11) [7]. A summary of the associations between diet/nutrition and the outcomes of ageing is presented in Figure 2.

Association between Nutrition and Physical Function
Seven studies [14][15][16][17][18][19][20], which included 48,674 participants, studied physical function components and how they are affected by ageing. Among these, physical function was assessed using the eight-item IADL scale [14][15][16], the Long-Term Care Insurance (LTCI) certification [17,19,20], or by the self-reported ability to conduct five self-care tasks (standing up after sitting for a long time, dressing, toileting, bathing, and feeding) [18]. Inconsistent findings were found regarding the association between the dietary diversity score and IADL limitation or incident disability, with one study showing a higher average dietary diversity score to be associated with a decreased risk of ADL disability (T3 vs. T1: hazard ratio, 0.50; 95% CI, 0.39-0.66) [18], while other studies reported null associations [16,17]. Regarding dietary patterns, greater adherence to various healthy dietary patterns [14,16,19], such as aMED, DASH, AHEI-2010, PDI, hPDI diet, fruit-egg-milk pattern, vegetable-meat-fish pattern, condiment and tea pattern, and the improved Japanese Diet Index, as well as increased adherence to the DASH diet [15], was significantly associated with a lower risk of IADL limitation or functional disability. For individual nutrients, data from the Ohsaki Cohort 2006 study showed that a higher consumption of green tea was significantly associated with a lower risk of incidents of functional disability, with a hazard ratio (95% CI) of 0.90 (0.77-1.06) among respondents who consumed 1-2 cups green tea/d; 0.75 (0.64-0.88) for those who consumed 3-4 cups/d; and 0.67 (0.57-0.79) for those who consumed ≥5 cups/d in comparison with those who consumed <1 cup/d (p-trend < 0.001) [20].

Association between Nutrition and Depression
Eight studies [13][14][15][21][22][23][24][25], which included 33,935 participants, investigated the components of depression in ageing. Among these, depression was assessed using the Center for Epidemiological Scale-Depression (CES-D) score [23][24][25], the Geriatric Depression Scale (GDS) [14,15,21], the Patient Health Questionnaire-9 (PHQ-9) [13], or the PhenX Toolkit [22]. As for dietary patterns, greater adherence to established healthy dietary patterns, such as the aMED, DASH, AHEI-2010, PDI, and hPDI diets [14], as well as an improvement in diet quality measured by these patterns [15], was associated with a lower risk of depression. However, for dietary patterns identified through a posteriori analytic methodology, while there were no significant associations of 'vegetables-fruits', 'snacks-drinks-milk products' and 'meat-fish' dietary patterns with a subsequent report of depressive symptoms among Chinese in Hong Kong [21], the vegetable-egg-beans-milk dietary pattern was associated with a lower risk of depression (OR, 0.65; 95% CI, 0.49-0.87), and the salt-preserved vegetable-garlic dietary pattern was associated with a higher risk of depression (OR, 1.33; 95% CI, 1.00-1.77) according to a study from the CLHLS [22]. For individual foods, higher intakes of soy products, fruits, and vegetables were associated with a lower risk of depression [13,24,25], whereas other food categories, including eggs, meat/poultry, seafood, dairy, legumes, grains, and tea, showed no significant associations [24]. Inconsistent results were shown for fish intake, with some studies reporting an inverse association [23] and others reporting null association [24].
For dietary minerals, higher intakes of potassium, calcium, magnesium, and selenium were associated with a lower risk of dementia [54,56,76] or a reduced likelihood of reporting memory decline [37], whereas a higher iron intake was associated with poorer cognitive function [36].

Association between Nutrition and Other Components of Healthy Ageing
For other components of healthy ageing, greater adherence to various healthy dietary patterns at midlife, as well as consistent or improved adherence to the DASH diet from midto late life, was associated with a higher likelihood of having good self-perceived health and physical functioning and a lower likelihood of having chronic diseases and functionlimiting pain [14,15]. In addition, a higher dietary diversity score was associated with less psychological stress (T3 vs. T1: OR, 0.59; 95% CI, 0.49-0.72); however, the association between the dietary diversity score and the number of comorbidities was insignificant [7].

Discussion
In this systematic review, we used data from population-based longitudinal cohort studies to investigate the prospective associations between nutrition at midlife and the likelihood of healthy ageing and its components in late life in Asia. Most of the current evidence has supported the positive associations of higher intakes of healthy foods at midlife, such as vegetables, fruits, fish, nuts, legumes, tea, milk, and dairy. Furthermore, a higher dietary diversity or total dietary antioxidant capacity at midlife, as well as greater or improved adherence to healthy dietary patterns from mid-to late life, was also associated with the likelihood of healthy ageing and its components in late life.
The currently available literature supports that adherence to various healthy dietary patterns is associated with a higher likelihood of healthy ageing. These healthy dietary patterns, either determined a priori or identified through a posteriori analytic methodology, are similar in that they recommend high consumption of fruits, vegetables, and whole grains; moderate consumption of dairy products, fish, and poultry; and low consumption of sugary beverages, saturated fat, added sodium, red meat, and processed food [14,16,19,39,40,43,54,64,71]. However, these results should be interpreted with caution, given that differences exist in the major ingredients and culinary methods used between Asian and Western cuisines. For example, the Mediterranean diet emphasizes fruits, vegetables, whole grains, and olive oil as staples, while Asian diets commonly rely on white rice, noodles, and other grains as primary sources of energy [72]. This variation in staple foods may significantly impact nutrient composition and overall dietary patterns.
In addition, the findings confirmed that maintaining consistently high DASH scores was related to a greater likelihood of healthy ageing than keeping consistently low DASH scores [15]. Moreover, those who managed to improve their DASH scores by >10% from mid-to late life were able to increase their likelihood of healthy ageing [15]. Hence, our findings provide evidence for the recommendation of the 2020-2025 Dietary Guidelines Advisory Committee that "it is never too late to eat healthfully" [78]. More studies are warranted to explore strategies in order to achieve a sustained change in dietary behaviours in the real world and to create an environment in which to make healthy eating affordable and accessible.
Dietary diversity is an important index reflecting nutrient adequacy. Increasing dietary diversity can ensure sufficient nutrient intake and improve dietary quality to promote healthy ageing [7,38]. However, mixed findings were observed regarding the association between dietary diversity score and IADL limitation or incident disability. Data from the CLHLS, including 2285 subjects aged >60 years with a maximum follow-up of 7 years, reported that dietary diversity had no effect on the occurrence of IADL limitation [16]. The Ota Genki Senior Project, including 10,318 Japanese adults aged >65 years with a median follow-up of 5.1 years, found that dietary variety was not independently associated with incident disability [17]. However, data from 5004 participants in a study of the CHNS reported that higher dietary diversity scores were associated with fewer physical functional limitations [18]. There are several potential reasons for these mixed findings. First, there is substantial variability in the measures of physical function and functional disability due to the use of different scales and instruments in different studies. Second, the intake frequency and scoring criteria of dietary diversity scores varied substantially across studies. For example, the dietary diversity score was calculated according to the intake frequency of 13 food groups, and the low group was defined as <7 in the CLHLS [16], whereas it was calculated according to the intake frequency of 10 food groups and a low group was defined as <3 in the Ota Genki Senior Project [17]. Nevertheless, our review concurs with the World Health Organization [79] and Chinese dietary guidelines [80] in terms of recommending adherence to a diverse diet to achieve healthy ageing in later life.
The associations between the intakes of fruits and fish and the likelihood of healthy aging components were inconsistent, and this could be explained by differences in the ranges of consumption among different populations. For example, the Hisayama study, which included 1071 Japanese participants, observed small differences among quintiles of fruit intake, with the range of the highest quartile of fruit intake being ≥115 g/d for men (≥100 g/d for women) and the lowest quartile being ≤32 g/d for men (≤21 g/d for women) [54]. However, there were substantial differences among the quartiles of fruit intake in the SCHS, with the median fruit intake in the highest and lowest quartile being 383.44 g/d and 76.30 g/d, respectively [50]. Notably, the SCHS applied a 165-item FFQ which included 14 fruits [50], whereas the Hisayama study applied a 70-item FFQ, and might have underestimated the fruit intake in this population [54]. Differences in methods of categorizing the intake of fish across studies could also explain these inconsistent results. For example, fish intake was divided into <3 times/week and ≥3 times/week in the Survey of Health and Living Status of the Elderly, and a null effect was reported for fish intake and risk of depression [24]. In contrast, fish intake was divided according to quartile consumption in the JPHC study, and a reduced risk of major depressive disorder was found in the third quartile (111.1 g/d) [23].
To the best of our knowledge, this is the first study which has systematically reviewed the association between nutrition in midlife and the likelihood of healthy ageing in late life according to Asian cohort studies. In addition, the quality of the included studies was considered to be high. Several limitations should be considered. First, except for the analyses of the association between nutrition and cognitive function, analyses related to healthy ageing, physical function, depression, and other components of healthy ageing only included limited studies. In addition, although we included 71 studies from 24 cohorts, these cohorts were situated in China, Japan, Singapore and Thailand, and represented a small proportion of the diverse Asian population. Second, substantial variations existed across the studies in terms of the measures of exposure, definitions of outcomes, sample sizes, and follow-up durations. Nonetheless, the overall results are consistent in that they recommend the consumption of healthy foods and adherence to healthy dietary patterns at midlife for healthy ageing. Moreover, improving the quality of one's diet from mid-to late life can still be beneficial.

Conclusions
The present study identified associations between nutrition at midlife and the likelihood of healthy ageing in late life using robust data from cohort studies in Asia. Our study's results provide important evidence for policymaking and dietary guidelines aimed at promoting healthy ageing in Asia.