First, let’s understand why people age, the main changes that reduce life expectancy.
Age-related changes in immune system function, a process called immunosenescence, are a major risk factor for increasing susceptibility of older people to disease. The main factor underlying immunosenescence is long-term antigenic stimulation throughout life. Age-related immunological changes are diverse among the elderly, and evidence suggests that there is an important relationship between the degree of frailty and immunocompetence.
Functions of innately adaptive “immune bridge” populations (natural killers, invariant natural killers, and T cells) seem to be better preserved with age than innate ones (neutrophils; monocytes/macrophages; myeloid-derived suppressor cells; and dendritic cells) or adaptive (T-cells – CD4+ and CD8+; B-cells) immune cells. Impaired neutrophil function leads to an increased risk of infectious disease that occurs in older people compared to younger people. At the cellular level, the number of neutrophils and adhesion abilities do not change with age, while chemotactic responses and migratory function decrease. In addition, some reports have shown that phagocytosis and production of reactive oxygen species by neutrophils decreases significantly with age.
Weakness is also associated with immune changes including
an increased ratio of neutrophils to lymphocytes and an increased content of myeloid-derived suppressor cells. This modification may explain the reduced ability of older people to elicit an immune response to antigens they have not previously encountered. In addition, there is an inversion
CD4:CD8 ratio; a decline in CD4+ T cells in the elderly is a marker of immuno aging and predictive of mortality.
In addition, aging is associated with increased levels of circulating cytokines and pro-inflammatory markers.
When debilitated, the immune phenotype is impaired due to chronic inflammation, known as the “inflammatory” phenotype, characterized by elevated levels of interleukin, C-reactive peptide, necrosis factor-alpha (TNF-α), interferon (IFN)-α, and transforming IFN-β. growth factor-β (TGF-β) and serum amyloid A
Chronic activation of T-like receptors, a consequence of the accumulation of reactive oxygen species during aging, also contribute to and exacerbate the inflammatory process.
Frailty, cardiovascular disease, and endothelial dysfunction
The prevalence of this type of aging increases in people over 65 years of age,
especially in persons over 75 years of age. Approximately 50% of patients with cardiovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, hypertension, heart failure with reduced ejection fraction develop epithelial tissue laxity. Moreover, frailty is a strong predictor of mortality in patients with cardiovascular disease. As shown in a meta-analysis of nine studies including 54,250 elderly patients, cardiovascular disease and frailty are associated with impaired inflammatory system. Several inflammatory biomarkers such as CRP, IL-6, factor VIII and D-dimer play a role in the pathogenesis of both processes.
Decreased performance of skeletal muscles
Sarcopenia, dynaponia, and loss of strength with age are important predictors of weakness. Sarcopenia is characterized by muscle degeneration caused with an altered pro-inflammatory state and is characterized by a progressive and generalized loss of skeletal muscle mass and strength. Circulating pro-inflammatory molecules affect the repair and renewal of many tissues, including skeletal muscle.
The chronic inflammatory state is characterized by a decrease in the synthesis and activity of insulin-like growth factor.
1 (IGF-1), which is critical to repair and maintain muscle integrity.
Inflammation also impairs the absorption of long branched chain amino acids, including leucine, isoleucine, tryptophan, serotonin, and methionine, which are essential for muscle anabolic processes.
HOW TO SLOW DOWN THE AGING PROCESSES
Decrease in the number of stem cells The lack of regenerative capacity of stem cells, leading to a violation of the ability to restore organs and tissues, is one of the main characteristics, which can be exacerbated by concomitant diseases. The function of stem cells is characterized by survival, proliferation, ability to differentiate, migrate and homing.
Aging is associated with the accumulation of random DNA damage, cell cycle arrest, and shortening of telomeres. These processes lead to a decrease in self-renewal, the ability to homing, and an increase in apoptosis under stress. The cellular aging biomarker p16INK4a accumulates and modulates age-related function. Transplantation of young stem cells significantly slows down the age-related loss of microstructure and bone density and increases life expectancy.
Based on clinical data indicating the beneficial effects of cell therapy in age-related conditions, the introduction of young stem cells has therapeutic value in improving health and delaying age-related decline in function.
Mesenchymal stem cells (MSCs) are multipotent progenitor cells.
characterized by self-renewal, formation of clonal cell populations, and multilinear differentiation. In addition to their antifibrotic, neoangiogenic, and cardiorepair properties, MSCs also have immunomodulatory properties.
MSCs affect the immune system in several ways. They play a role in the regulation of the innate immune response by inhibiting the maturation and antigen-presenting ability of dendritic cells, as well as reducing the proliferation and cytotoxicity of natural killer cells.
They also suppress the adaptive immune response by inhibiting both CD4+ helper and CD8+ proliferation and function of cytotoxic T cells and B cells. Additional immunomodulatory effects of MSCs are manifested through direct intercellular
the contact includes the induction of regulatory B cells and T cells, as well as the deviation of monocytes/macrophages and dendritic cells from an anti-inflammatory phenotype. Moreover, recent evidence suggests that MSCs in an inflammatory environment induce phenotypic and functional changes in monocytes, which then modulate the adaptive immune cell. These immunoregulatory properties of MSCs offer new insights into the potential treatment of injury and inflammation in any tissue. Apart from
anti-inflammatory action, antimicrobial action are also related to MSCs, including direct inhibitory action on bacterial growth and indirect effects through the secretion of immune mediators that activate inflammatory cells. MSCs enhance the microbicidal activity of macrophages by promoting the conversion of naive macrophages into inflammatory M1 macrophages without enhancing their antigen-presenting cellular function in response to pathogenic injury. These properties of MSCs promote patient response to invading pathogens, which may be of value in preventing or treating debility that greatly exacerbates morbidity and mortality.