Fight Aging!

What can be found in a human blood sample that either correlates with or predicts exceptional healthspan or lifespan? Quite the variety of research efforts touch on this question, from the development of aging clocks to the construction of omics databases for blood and tissue samples taken from centenarians. People age as a result of the same underlying processes of damage and dysfunction, but the pace of aging clearly varies widely. It is generally accepted in the research community that efficient ways to measure the state of biological aging are needed in order to speed the development of therapies to treat aging. Without the ability to rapidly determine the effects of an alleged anti-aging therapy immediately after administration, the only recourse is to wait and see. Thus animal studies are expensive and slow, research can be stuck for years in a dead end that only later is shown to be not so great, and human data is non-existent, as no-one will fund ten year clinical studies for potential drugs.

Today's open access review paper surveys some of the work conducted to date in search of signatures of longevity that can be measured in blood samples and other non-invasive assays. In some cases, signatures can be plausibly connected to processes relevant to longevity, such as suppression of the chronic inflammation of aging. In other cases, no-one really knows why the correlation exists. It also remains a question, on a case by case basis, as to whether ways to adjust the signature will also slow aging to some degree; in most cases, probably not, as the signature is a downstream consequence of underlying processes and causes little further harm in and of itself.

The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics

In this review, we integrate longevity-related biomarkers discovered by metabolomics and proteomics and further categorize them based on different classes. The mechanisms of longevity-related metabolites have been elucidated, especially for specific fatty acids like EPA, DHA, and short-chain fatty acids, which effect lifespan by reducing inflammation and activating the Nrf2 pathway. The mechanisms underlying the health benefits of the changes in certain metabolites are still largely unknown. For example, the mechanism of some isomers of secondary bile acids affects the body's immunity remains to be further studied. Additionally, the metabolic pathways and products of metabolites should also be considered. Some intermediates (such as kynurenic acid) have neuroprotective effects, which were produced from tryptophan. Regarding proteins, APOE, FOXO, and SIRT are essential signaling proteins for cell survival, which can regulate cell proliferation, metabolism, inflammation, and stress responses by influencing multiple signaling pathways, including PI3K/Akt, NF-κB, etc. Moreover, post-translational modifications such as nitrosylation and glycosylation have important effects on the function and communication of proteins. The interaction between various modifications and star proteins creates a complex network that modulates cell survival to extend lifespan. Therefore, integrating candidate longevity-related biomarkers to conduct a "biomarker library of health and longevity" can further grasp the profile of centenarians or extreme longevity in humans and provide a theoretical foundation for anti-aging.

Appropriate analytical methods are crucial for different research objects based on the research question and sample characteristics. In metabolomics, untargeted and targeted metabolomics both have different advantages and disadvantages. It is worth noting that a certain degree of lipid metabolism dysfunction and neural functional damage happens during the aging process. Therefore, targeted metabolomics focusing on specific metabolites such as short-chain fatty acids, bile acids, and neurotransmitters can better reflect the physiological status of the elderly. In proteomics, general proteomics can provide a more comprehensive protein map for the longevity population. With an increase in age, protein homeostasis gradually declines and results in wrong translation modification such as nitrosylation and glycosylation. Consequently, post-translational modifications of proteins are considered crucial indicators affecting the function of proteins. The study of longevity cohorts based on untargeted metabolomics and general proteomics has been extensively reported. We regard that targeted metabolomics and PTM proteomics focusing on specific biomolecules will attract more attention in aging studies to discover more valuable longevity-related biomarkers, whether metabolites or proteins. Moreover, blood and fecal samples are commonly preferred for biomarker discovery due to their relatively easy access. If tissue-specific characteristics are exhibited in the liver or muscle tissues of centenarians, it potentially leads to obvious alterations in circulating blood metabolites. However, there are significant challenges in obtaining tissue samples such as liver and muscle from living individuals. We wish that better technology may have appeared in the future to offer the possibility to analyze the tissue or organ specificity of centenarians.