Nutrition and Healthy Aging

Dietary restriction (DR) is a widely used experimental intervention in aging research due to its consistent ability to extend lifespan in most species tested. DR is an all-encompassing term describing interventions that restrict some aspect of nutrition - from calorie amount to calorie type to timing of food intake - and yet share common functional endpoints including extended longevity, but also improvements in healthspan, or the time spent in good health, as well as metabolic fitness and stress resistance. Recent studies highlight the preponderance of sexual dimorphisms in the response to DR and argue for the importance of inclusion of both sexes in preclinical research.

We set out to perform a comprehensive assessment of documented health and lifespan outcomes of interventional DR studies in mice that display sexual dimorphism.

A systematic literature search was conducted according to the PRISMA statement to identify mouse DR studies in which both sexes were included using PubMed. The specific DR interventions examined included calorie restriction (CR), intermittent fasting (IF), protein restriction (PR) and methionine restriction (MetR), with experimental endpoints focused on lifespan and healthspan.

Sexual dimorphism in the lifespan and healthspan effects of various DR regimens is a common finding in mice, with the magnitude and direction of dimorphic responses influenced by the specific dietary intervention as well as the strain of mouse used in the study.

Despite the fact that preclinical lifespan and healthspan analyses in mice reveal sexual dimorphism in the response to DR, there is still a large gap in our understanding of how sex affects dietary outcomes. More preclinical research comparing both sexes in the same study with better attention to reporting metrics during peer review and in easily searchable text including title and abstract is required to further our understanding of the impact of sex on health and lifespan in response to DR in rodent studies.

Changes in DNA methylation along the life have been documented, and environmental exposures (including diet, physical activity and smoking) can accelerate or decelerate this process. The epigenetic clock estimates the biological age of an individual measuring methylation patterns in specific areas of its genome. Recently, a new epigenetic clock based on 6 CpGs has been proposed, with high potential to become an easy accessible tool able to measure the epigenetic age (EA) of an individual.

This study aims to validate the 6 CpG epigenetic clock comparing it with other biomarkers of aging such as telomere length (TL) and methylation in the long interspersed nuclear element-1 (LINE-1). The impact of lifestyle associated factors on these molecular marks has been evaluated.

200 healthy participants having extreme dietary patterns (healthy vs western diet) were selected. Dietary intakes, body composition, physical activity level and smoking has been assessed. DNA extracted from whole blood was used to measure the 6CpG-EA, TL and LINE-1 methylation levels.

6CpG-EA was positively correlated with chronological age (r = 0.591; p = 7.2*10^-20) and negatively with TL (r = –0.150; p = 0.040) and LINE-1 methylation (r = –0.240; p = 0.001). Despite the fact that no significant associations were detected with the overall diet quality (HEI), 6CpG-EA was correlated with dietary intakes of nutrients involved in the one-carbon (1 C) metabolism, especially in the western diet group.

These results support the 6CpG epigenetic clock as an easy accessible tool to estimate biological age, in accordance with other molecular markers of aging, and suggest that EA can be modulated by micronutrients involved in the 1 C metabolism.

An altered plasma fatty acid (FA) profile and desaturase activities have been associated with several metabolic diseases, including the MetS, but studies in the general populations are lacking, and only few studies have investigated a broad spectrum of FA in plasma phospholipids (PL).

We investigated, cross-sectionally, the relationship of the FA profile and desaturase activities in plasma PL with the prevalence of MetS in a general population in The Netherlands.

Baseline characteristic data from 850 participants (male: 50.2%) aged 38-68 years recruited in the Lifelines cohort study were obtained. The FA profile was determined in fasting plasma PL, and desaturase activities were estimated from product/precursor ratios. The MetS was defined according to International Diabetes Federation. Logistic regressions were used to examine the relation of the FA profile with the prevalence of MetS, and Bonferroni correction was applied to account for multiple testing.

151 participants (17.7%) had the MetS. After adjustment for several confounders and Bonferroni correction, higher tertiles of C18 : 0 (the early precursor of de novo lipogenesis pathway), C18 : 3n6 and C20 : 3n6 (both consistent with a high Δ⁶ desaturase (D6D) activity), and D6D activity itself were associated with a higher prevalence of MetS, while higher tertiles of C18 : 1n7, C24 : 0, and C24 : 1n9 (very long chain FA) as well as stearoyl-CoA desaturase (SCD)-18 were inversely associated with the MetS.

This study shows that a wide-ranging plasma PL FA profile and estimated desaturase activities were different between adults with and without the MetS in a general representative population and implicates the importance of monitoring individual FAs and desaturase activities as novel modifiable biomarkers for the MetS.

Omega-3 fatty acid (OM3) intake is associated with a lower risk of developing Alzheimer’s disease, but individuals carrying the ɛ4 allele of apolipoprotein E (APOE4) might not benefit from this prevention strategy. Indeed, they might have lower OM3 into plasma free fatty acid (FFA) and lysophosphatidylcholine (LPC) compartments, the two forms the brain can take-in.

To evaluate the docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations in the FFA and LPC pre- and post-OM3 supplementation in APOE4 carriers and non-carriers.

Plasma samples from 25 APOE4 carriers and non-carriers before and six months after receiving 2.5 g/d DHA+EPA daily were analyzed. DHA and EPA concentrations in the LPC, and FFA were compared by supplementation and genotype. A secondary analysis investigated the interaction between body mass index (BMI) and APOE genotype status.

There was no genotype x supplement interaction nor a genotype effect on LPC and FFA. However, there was a supplement effect where OM3 increased in all lipid compartment by < 1-fold to 4-fold. Individuals with a low BMI had higher OM3 increase concentrations in the LPC than those with a high BMI.

APOE4 carriers and non-carriers can both benefit from taking an OM3 supplement. However, individuals with a high BMI have lower OM3 increases than those with a lower BMI.

Pecans are rich in nutrients known to benefit cognition.

To examine the effect of daily pecan consumption on cognitive function in older adults.

In this randomized controlled trial, 42 adults (50–75y) either consumed 68 g of pecans/day for 4-weeks (pecan; n = 21) or avoided all nuts (control; n = 21). At pre- (V1) and post-intervention (V2) visits, cognitive function was assessed using a fluid composite score and four subtests from the NIH Toolbox-Cognitive Battery (NIHTB-CB) (Flanker Test, Digital Change Card Sort Test (DCCS), Picture Sequence Memory Test (PSMT), NIHTB Auditory Verbal Learning Test (RAVLT)) at fasting, 30- and 210-min after a high-saturated fat meal void of pecans.

From V1 to V2, fasting and postprandial cognitive performance did not differ between groups. There were improvements in both groups for fasting fluid composite score (p < 0.001) and performance on RAVLT, PSMT, DCCS, and Flanker tests from V1 to V2 (p < 0.001 for all), with no differences between groups. Additionally, postprandial performance on RAVLT, PSMT, and Flanker tests improved at V2 (p < 0.01 for each), with no differences between groups.

A short-term pecan-enriched diet did not provide additional cognitive benefits in healthy older adults in the fasted or postprandial state.

Due to better health care and improved nutritional status of the world’s population, many people live into old age. This has resulted in more diseases related to aging, such as neurodegenerative diseases. Bacopa monnieri (BM) is a medicinal herb found in Southeast Asia and is a popular memory-enhancing supplement.

This study aimed to investigate how BM may provide protection in neurodegenerative disease, and whether the sigma-1 receptor is involved.

PC-12 cells were differentiated with the addition of nerve growth factor. The potentiation by BM of PC-12 neurite growth was measured by counting the number of differentiated cells and by measuring their length. Differentiated PC-12 cells were also subjected to amyloid-β (Aβ) toxicity in the presence and absence of BM. The cell survival (MTT and cell counting) and neurite lengths were then measured as indicators of cellular health. Total protein was extracted from control and treated cells and expression of various signalling pathway molecules was assessed via western blotting. We also assessed the effects of BM on the lifespans of various mutant strains plus wild-type C. elegans.

We show that BM can protect against Aβ toxicity in PC-12 cells. Furthermore, BM can potentiate neurite outgrowth in PC-12, in a sigma-1 receptor antagonist sensitive fashion, and Neuro2A cell lines. BM induced a reduction in pAKT expression and upregulated BDNF expression in PC-12 cells. BM was also able to increase the lifespan and health-span of Aβ expressing C. elegans mutants via the DAF-16 mediated pathway. BM reduced oxidative stress in wild-type C. elegans exposed to UV-A with pre-exposure and post-exposure treatments.

This all further identifies BM as a potential agent to treat neurodegenerative diseases, by modulating different pathways.

Coronavirus disease-19 (COVID-19) has caused significant morbidity and mortality worldwide. Diabetes mellitus (DM) and related comorbidities have a significant impact on clinical presentation and outcomes. The aim is to compare clinical presentation and outcomes among COVID-19 patients with or without DM.

Data from 312 patients who tested positive for COVID-19 at a single hospital were collected respectively from January to April 2021. It included demographic data, clinical symptoms, underlying comorbidities, clinical chemistry, and hematological laboratory findings. Different inflammation indices were calculated. The findings of COVID-19 diabetic and non-diabetic patients were compared.

The percentage of COVID-19 patients with DM and hypertension or cardiovascular diseases was significantly higher compared to non-diabetic patients (78.6 % vs. 35%, and 46.4% vs. 23%, p < 0.001) respectively. The diabetic patients showed a significant increase in D-dimer and alkaline phosphatase levels (1922.2 vs.1154.5, p = 0.007 and 85.3 vs.75.5, p = 0.01) respectively. On the other hand, diabetic patients showed a significant decrease in serum albumin (3.5 vs.3.6, p = 0.012). The mean death probability indicator (ANDC), and ICU admission were higher in diabetic patients (72.2%, and 36.6%; respectively) versus the non-diabetic patients (60.7% and 26.1%; p < 0.001, 0.071; respectively). Also, the estimated glomerular filtration rate (eGFR) was significantly higher in diabetic patients as compared to non-diabetic patients.

The diabetic patients had more comorbidities, a higher rate of ICU admission.

The literature suggests that nutritional status is associated with the onset and maintenance of depressive symptoms, but the association is still unclear.

Describe the association between malnutrition and depressive disorder.

Cross-sectional study, in 221 non-randomly selected, community dwelling, individuals. Data were collected through individual, face-to-face interviews, which included questions on health, nutritional status, sociodemographic characteristics, and the interviewer versions of the Mini Nutritional Assessment and the Geriatric Depression Scale. Statistical analyses were conducted using IBM SPSS Statistics 27.0, and statistical significance for all procedures was set at 0.05.

The most prevalent clinical feature was pain during the last month (73.3%). 58 participants (26.2%) were at risk for malnutrition and 2 participants (0.9%) presented malnutrition. Depression was more prevalent in women (55.3%) than in men (37.5%). Odds to exhibit depression are 1.83 times higher (95% CI 1.16–3.68, p = 0.036) with malnutrition and 2.45 times higher (95% CI 1.25–4.78, p = 0.009) if reporting pain.

Clinicians should consider the assessment and intervention for both depression and malnutrition when encountering one of these conditions. Acute pain seems to have a strong association with depression and must also be addressed and considered in this regard.