ReviewChanges in plasma phospholipids and sphingomyelins with aging in men and women: A comprehensive systematic review of longitudinal cohort studies
Introduction
Aging is an intricate process that influences metabolic pathways and plays a crucial role in the incidence of chronic health conditions, such as cardiovascular complications, cancer, and neurological disorders (Harman, 1981). Beyond chronological aging, biological aging could be affected by many potential factors, including diet and genetics (Gieger et al., 2008; Low et al., 2019). Metabolomics has been used to identify predictors of healthy aging based on the levels of some metabolites that vary across pathological conditions (Idle and Gonzalez, 2007). Therefore, identifying altered metabolites during aging may provide valuable information regarding the pathogenesis of chronic diseases (Sprott, 2010).
The relationship between metabolomics and aging has drawn interest over the past few years (Weckwerth, 2003). Lipidomics, a subset of metabolomics, focuses on the identification and quantification of human lipids, which includes a vast range of metabolites (Wenk, 2005). As most of these small biomarkers represent the endpoint of cellular and molecular regulatory processes and their complex networks, they can be considered reliable proximal biomarkers of chronic disease (Wenk, 2005). It has been shown that the composition of the plasma lipidome significantly varies with increasing age (Yu et al., 2012; Darst et al., 2019a, 2019b). For example, levels of some phosphoglycerides (PG) increase during aging, while others decrease (Auro et al., 2014; Dorninger et al., 2018). Similarly, it has been shown that sphingomyelin (SM) levels change with age depending on the species of SM (Mielke et al., 2015; Darst et al., 2019a, 2019b). Differences in the plasma lipidome between men and women have also been observed (Ishikawa et al., 2014; Krumsiek et al., 2015) and some have been linked with age (Chak et al., 2019; Wong et al., 2019). For example, it has been demonstrated that levels of SMs increase in women and decrease in men during healthy aging (Mielke et al., 2015). This difference could be attributable to the distinct body composition and hormonal differences between sexes (Wang et al., 2018a, 2018b).
The levels of some lipid metabolites may be influenced by pathological conditions. For instance, disruption in the normal pattern of change in SM levels with aging is associated with developing Alzheimer’s disease (AD) (Mielke et al., 2015; Wong et al., 2019). Similarly, increases in acylcarnitine levels are correlated with an increase in risk of type 2 diabetes (Mihalik et al., 2010). These examples suggest that lipidomics investigations could reveal valuable information regarding the pathogenesis of age-related chronic diseases. Because changes in the amount of plasma lipid metabolites may be sex-dependent, we conducted a systematic review of aging-related changes in the plasma lipidome in men and women. The review was restricted to studies assessing / multiple measures per person to remove variability and potential confounding due to the strong genetic determinants of the metabolome, and possible bias due to selective survival.
Section snippets
Methods
Present systematic review was focused on the changes of plasma phospholipids and sphingomyelins with aging in healthy male and female subject in older age groups (>60 years).
Study selection
A total of 1470 studies were identified. After removing 592 duplicates, the remaining 878 studies’ titles and abstracts were screened. Based on inclusion criteria, 784 studies were considered irrelevant and excluded. The full texts of the remaining 94 articles were evaluated, and, among these, 8 studies fully met our specified inclusion criteria. However, one of these studies (Zheng et al., 2017) only reported the fatty acid composition of phospholipids, and was therefore excluded. Also,
Discussion
Through our comprehensive systematic review, we identified 6 articles comprising 7 independent cohorts that prospectively evaluated the relationship between aging, sex, and changes in the plasma lipidome. The results indicate that the plasma lipidome changes with aging and that these changes are dependent, in part, on sex. Among the studies included in our review, the overall levels of PC decreased in males and increased in females with aging. Similarly, almost all studies investigating SM
Conclusion
The systematic review presented here found that overall levels of PC, SM and PE, regardless of their subtypes, increase in females during aging. In males, PC, LPC and SM levels decrease during aging. It should be noted, however, that there were some inconsistencies across studies. The results obtained regarding LPC were more inconsistent compared to other metabolites and require further investigation. Sex-specific changes in SM levels were more consistently identified across studies, whereas
Author contribution
NMH: Contributions to concept/design, Data interpretation, drafting of the manuscript, Acquisition of data, Approval of the article; MZ: Data interpretation, Acquisition of data, Literature search, Drafting of the manuscript, Approval of the article; SAM: Critical revision of the manuscript, Contributions to concept/design, Approval of the article; AA: Critical revision of the manuscript, Contributions to concept/design, Approval of the article.
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgement
This study is supported by NIH/NINDS funding (Grant number: 3R01NS089619-05S1).
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