Immunosenescence: molecular mechanisms and diseases

Abstract

Infection susceptibility, poor vaccination efficacy, age-related disease onset, and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging (known as immunosenescence). During aging, organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers, termed inflammaging. This chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related diseases. Thymic involution, naïve/memory cell ratio imbalance, dysregulated metabolism, and epigenetic alterations are striking features of immunosenescence. Disturbed T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells, and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates inflammaging. Although the underlying molecular mechanisms remain to be addressed, it is well documented that senescent T cells and inflammaging might be major driving forces in immunosenescence. Potential counteractive measures will be discussed, including intervention of cellular senescence and metabolic-epigenetic axes to mitigate immunosenescence. In recent years, immunosenescence has attracted increasing attention for its role in tumor development. As a result of the limited participation of elderly patients, the impact of immunosenescence on cancer immunotherapy is unclear. Despite some surprising results from clinical trials and drugs, it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.

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“…6 Unlike germ cells and certain stem cells, most somatic cells undergo a finite number of divisions in culture before permanently ceasing to divide, entering a state referred to as cellular senescence or replicative senescence. 7,8 In fact, cellular senescence is a common phenomenon observed in various organisms, representing a relatively stable state where cells have irreversibly exited the cell cycle and lost their proliferative capacity. 9 Unlike apoptosis, senescent cells irreversibly arrest at the G1 phase of the cell cycle, no longer dividing, and lose the ability to synthesize DNA and undergo cell division, while still maintaining their basic metabolic processes.…”

“…In recent years, cellular senescence has emerged as a novel approach for targeting the perpetual growth of tumor cells and has become a focal point of research for cell biologists 6 . Unlike germ cells and certain stem cells, most somatic cells undergo a finite number of divisions in culture before permanently ceasing to divide, entering a state referred to as cellular senescence or replicative senescence 7,8 . In fact, cellular senescence is a common phenomenon observed in various organisms, representing a relatively stable state where cells have irreversibly exited the cell cycle and lost their proliferative capacity 9 .…”

Effect of C-to-T transition at CpG sites on tumor suppressor genes in tumor development in cattle evaluated by somatic mutation analysis in enzootic bovine leukosis

“…2A). This finding may be linked to immunosenescence [35]; the decline in the functions of the immune response due to aging causes a weakened elimination of precancerous abnormal cells, creating a tumor-prone condition. Considering that mutation frequencies of TP53 gene in diffuse large B-cell lymphoma, one of the nonviral and sporadic human cancers, range from 17.6% to 23.2% [36], the development of EBL in very old cattle may resemble that of spontaneous tumors rather than virus-associated tumors.…”

Unlocking the potential of T‐cell metabolism reprogramming: Advancing single‐cell approaches for precision immunotherapy in tumour immunity

“…On the other hand, it could activate downstream SREBPs and participate in the expression of fatty acid synthesis enzymes (FASN, ACC, etc. ), regulating lipid metabolism 147,169 . PIM kinase, a member of the serine/threonine kinase family, controls the phosphorylation of various proteins involved in cellular metabolism and survival and is closely associated with mTORC1 signalling activity to influence CD8+ T‐cell memory state formation 170 .…”