Evaluating the nutrient 
                                                                                           needs of older adults and 
                                                                                     actionable steps to support 
                                                                                                                       immune function
                                                                                                                                            SPEAKER BIOGRAPHY
                     Prof. Ascensión Marcos, PhD
                     Head of the Immunonutrition 
                     Research Group, Institute of                         Prof. Ascensión Marcos is a pioneer in the field of Immunonutrition in Spain. 
                     Science, Technology of Food and                      She is the Head of the Immunonutrition Research Group at the Institute of 
                     Nutrition (ICTAN). Spanish 
                     National Research Council (CSIC).                    Science, Technology of Food and Nutrition (ICTAN) at the Spanish National 
                     Madrid, Spain.                                       Research Council (CSIC). Her research focuses on varying aspects of 
                                                                          immunonutrition and her scientific contributions have been recognized with a 
                                                                          number of awards and honours. She has completed 95 research projects and 
                                                                          578 publications (papers, reviews, book chapters, etc.). Prof. Marcos holds a 
                                                                          number of leadership positions, including President of the International Society 
                                                                          for Immunonutrition (ISIN), Treasurer of the Spanish Nutrition Society, and 
                                                                          Past-President of the Federation of Spanish Societies of Nutrition, Food and 
                                                                          Dietetics (FESNAD). She is involved in the Institutional Affairs Spanish Society of 
                                                                          Microbiota, Probiotics and Prebiotics (SEMiPyP), Founder and President of the 
                                                                          International Forum of Immunonutrition for Education and Research (i-FINER) 
                                                                          between 2007-2014, and the Past-President of the Federation of European 
                                                                          Nutrition Societies (FENS) between 2015-2019. Prof. Marcos got her PhD at the 
                                                                          School of Pharmacy at the Complutense University in Madrid, Spain (UCM), and 
                                                                          her Master in Clinical Analysis by UCM.
                                                                          ABSTRACT:
                                                                          Ageing is defined as ‘‘the regression of physiological function accompanied by 
                                                                          the development of age’’. The effects of aging alter not only the capabilities but 
                                                                          also the effectiveness of the immune system.
                                                                          The term “Immunosenescence” reflects the aging of the immune system, 
                                                                          describing alterations and reflecting inappropriate increases, decreases, and 
                                                                          dysregulated immune reactivity in the elderly.
                                                                          The consequences are an increased susceptibility to infections and their 
                                                                          severity, along with a lower efficacy of the vaccines and a higher incidence of 
                                                                          tumors.
                                                                          This scenario leads to a chronic low-grade inflammation, called inflammaging, 
                                                                          which together with the action of pollutant agents, recurrent infections, 
                                                                          unhealthy lifestyles, and obesity, leads to an increase in morbidity and mortality.
                                                                          In addition, there is a strong interrelationship between the immune system and 
                                                                          the microbiota. Indeed, experimental evidence has shown that reduced levels 
                                                                          and variations in the bacterial community are associated with health 
                                                                          impairments, while increased microbiota diversity improves metabolic profile 
                                                                          and immunological responses.
                                                                          Elderly people show a reduced number of bifidobacteria that are among the first 
                  microbes to colonize the human gastrointestinal tract and are believed to exert positive 
                  health benefits, such as treating various gastrointestinal disorders (diarrhea, 
                  constipation) and diseases, like colorectal cancer. Indeed, the ageing process deeply 
                  affects the structure of the human gut microbiota, and also, the homeostasis between gut 
                  microbiota and the immune system.
                  Unfortunately, with the arrival of SARS-CoV-2, we have seen how the elderly population 
                  has been the most attacked by COVID-19, and it is when we have realized the importance 
                  of nutrition and its great role in the preservation of the immune system and the 
                  maintenance of a healthy microbiota.
                  In this context, there is evidence regarding the capability of many bioactive compounds, 
                  such as vitamins, minerals, polyphenols, fatty acids, prebiotics and probiotics, some of 
                  them already established during years and others emerging as potential ingredients, 
                  interacting among them, enhancing the microbiota composition, modulating the immune 
                  system, preventing inflammatory diseases, and promoting health. 
                  Therefore, we cannot deny the important role played by diet, food and dietary 
                  components, and it is also plausible to assume that some of their anti-inflammatory and 
                  antiviral effects could potentially contribute, at least partially or in combination with other 
                  medications, in prevention and/or alleviation of COVID-19-related symptoms.
                  Indeed, there is a strong interaction between the nutritional status and the immune 
                  system and both small deficits and chronic excesses or even the imbalance between 
                  nutrients, can jeopardize the stability of the metabolism in general. 
                  Moreover, it is very important not to forget the risk factors throughout life that develop 
                  all the non-communicable diseases, such as inactivity, obesity, smoking, excessive 
                  alcohol consumption, sleep problems, stress and obviously an unhealthy diet.
                  In addition, there is a bidirectional communication system between the gut microbiota 
                  and the brain. Thus, brain modulates the gastrointestinal function and any alteration in 
                  gastrointestinal function is communicated to the brain with the perception of visceral 
                  events (nausea, satiety, pain). Both the nutritional status and the immune system are also 
                  linked to the gut-brain axis. Therefore, the study of Immunonutrition covers all these 
                  matters and their interactions (figure), being key to understanding the nutritional 
                  situation and valid to promote life quality in order to prevent infections and inflammatory 
                  diseases.
                   
                  Normally, cells depend on antioxidants for protection from OxS, and glutathione (GSH) is 
                  the most abundant cellular antioxidant. Aging is associated with both increased OxS and 
                  with GSH deficiency, and this compromised antioxidant defense further amplifies the 
                  destructive potential of OxS in aging. Therefore, GSH is a vitally important antioxidant to 
                  sustain cellular health [4-6] and it becomes necessary to understand why GSH deficiency 
                  occurs and how to correct it, and understand the benefits of GSH restoration. Dr. Sekhar 
                  hypothesized that GSH deficiency in aging was responsible for OxS, mitochondrial 
                  dysfunction and for multiple additional abnormalities linked to aging and other diseases 
                  [7-15]. 
                  GSH is a tripeptide composed of 3 amino-acids, glycine, cysteine and glutamic acid. 
                  Dr. Sekhar  investigated and found that GSH deficiency occurs due to decreased cellular 
                  synthesis caused by decreased availability of two of its precursor amino-acids glycine 
                  and cysteine [8]. There are some challenges to correcting GSH deficiency, and doing this 
                  safely. GSH deficiency cannot be corrected by direct supplementation of GSH orally 
                  (because it is digested in the gut) or intravenously (because it is impractical and has 
                  significant risks). Providing cysteine directly is also impractical because it is oxidized in 
                  the gut. There is another important consideration – while excess ROS is toxic and gives 
                  rise to damaging OxS, cells need a small amount of ROS to maintain cellular health. 
                  If levels of ROS are excessively lowered this gives rise to ‘reductive stress’ (RedS), which 
                  is also toxic and harmful to cellular health. Therefore, cells have to manage a very 
                  delicate balancing act between preventing both OxS and RedS, and they do this by 
                  regulating synthesis of GSH in a highly controlled manner. An inherent challenge with 
                  antioxidant supplementation is how to target OxS and simultaneously avoid RedS, and 
                  this applies to correcting GSH deficiency in aging. 
                  Dr. Sekhar’s research led to the discovery that supplementing GlyNAC, a combination of 
                  glycine and N-acetylcysteine (NAC, a cysteine donor), is able to correct deficiencies of 
                  glycine, cysteine, glutathione and lower OxS without any development of RedS. 
                  His clinical trials in older humans supplemented GlyNAC for up to 24-weeks and found 
                  this to be safe and highly effective in providing cellular protection (by correcting GSH 
                  deficiency, lowering OxS and decreasing damage due to OxS), correcting abnormalities in 
                  cellular energy generation (by correcting mitochondrial dysfunction), lowering cellular 
                  injury (by decreasing inflammation, insulin resistance, endothelial dysfunction), 
                  decreasing damage to our genes, increasing muscle strength and exercise capacity, 
                  reversing cognitive decline, and decreasing abdominal obesity [7-9].  His work in basic 
                  science has shown that GlyNAC supplementation in old mice can improve cardiac 
                  function [10], and his clinical trials in older humans and HIV-patients show the potential 
                  impact of GlyNAC on improving brain health, muscle health, and quality of life [7, 12-14]. 
                  In his presentation at the EuGMS, Dr. Sekhar will discuss age-associated abnormalities in 
                  glutathione, oxidative stress, reductive stress, mitochondrial function, metabolic defects 
                  and hallmarks of aging, and present the results and health implications of GlyNAC 
                  supplementation and GlyNAC withdrawal in older humans, as outlined in his recently 
                  published clinical trial in aging.