Complexity of Anti‐immunosenescence Strategies in Humans

Abstract

Immunosenescence is characterized by three main aspects: (i) the shrinkage of the T cell repertoire and the accumulation of oligoclonal expansions (megaclones) of memory/effector cells directed toward ubiquitary infectious agents; (ii) the involution of the thymus and the exhaustion of naïve T cells; and (iii) a chronic inflammatory status called inflamm-aging. We present here possible strategies to counteract these main aspects of immunosenescence in humans with particular attention to the reduction of antigenic load by pathogens, such as CMV, and the normalization of intestinal microflora, the possible utilization of IL-7 to reverse thymic involution, the purging of megaclones, the forced expression of CD28 on T lymphocytes, the reduction of inflamm-aging and the administration of nutrients such as vitamin D. Possible drawbacks of all these strategies are discussed. Finally, the complexity of a rejuvenation approach is stressed, with particular attention to the inhibitory role played by the "old microenvironment" on the performance of progenitor cells, the best candidate to counteract the decline in regenerative potential characteristic of organs and tissues from old organisms.

Age-Related Inflammation: the Contribution of Different Organs, Tissues and Systems. How to Face it for Therapeutic Approaches

“…In any case, this antiimmunosenescence strategy needs further knowledge of dendritic cells and of their role in oral tolerance. A wide range on dendritic subpopulations is present at the mucosal immune system, some of the lineage and subset being still poorly known [39,40].…”

“…First of all, careful attention should be paid to neglected sources of antigenic stimulation, such as chronic, subclinical infections in the oral cavity and the gastrointestinal and urogenital tracts, amongst others, which probably represent a major source of chronic antigenic stimulation. From this point of view, a systematic search for chronic infections, and the setup of safe procedures to eradicate them, would be likely to have a strong, beneficial impact on health status and functional capability, but also on overall survival and life span in the elderly [39].…”

“…Therefore, the elucidation of the intestinal microbiome is likely to underpin future disease prevention strategies, personalized health care regimens, and the development of novel therapeutic interventions that takes into account the complex genetic scenario including genes embedded in human affiliated microbiome, accounting alone for > 100 times as many genes as those of the human genome [39,40].…”

Aging of the Immune System as a Prognostic Factor for Human Longevity

“…However, certain other functional characteristics of neutrophils from elderly individuals, such as superoxide anion production, chemotaxis, and apoptosis in response to certain stimuli, are reduced ( Immunosenescence and Inflamm-aging, by intimately changing the body microenvironment, have systemic effects on a variety of organs and systems and must be envisaged and conceptualized within a broad perspective, such as that proposed by Systems Biology, an approach that can help us to grasp its complexity and possibly to formulate rational anti-immunosenescence strategies (9,106). To this end, an overview of the multiple facets of immunosenescence will be given in the next section on age-related changes in innate and adaptive immune functions.…”

Inflammaging- Altern als Konsequenz chronischer Entzündungen: Das Beispiel Padma 28

“…Dies hat einerseits eine reduzierte Plastizität der Immunabwehr zur Folge, andererseits führen solche Prozesse zur Entstehung eines proinflammatorischen Milieus im Körper [3,4]. Der daraus entstehende chronische, unterschwellige Entzündungszustand äus-sert sich in der Zunahme verschiedener Entzündungsfaktoren und wird nach FRANCESCHI mit dem Begriff Inflammaging umschrieben [2,5,[6][7][8].…”