Aging and Age-Related Epigenetic Drift in the Pathogenesis of Leukemia and Lymphomas: New Therapeutic Targets

Abstract

One of the traits of cancer cells is abnormal DNA methylation patterns. The idea that age-related epigenetic changes may partially explain the increased risk of cancer in the elderly is based on the observation that aging is also accompanied by comparable changes in epigenetic patterns. Lineage bias and decreased stem cell function are signs of hematopoietic stem cell compartment aging. Additionally, aging in the hematopoietic system and the stem cell niche have a role in hematopoietic stem cell phenotypes linked with age, such as leukemia and lymphoma. Understanding these changes will open up promising pathways for therapies against age-related disorders because epigenetic mechanisms are reversible. Additionally, the development of high-throughput epigenome mapping technologies will make it possible to identify the “epigenomic identity card” of every hematological disease as well as every patient, opening up the possibility of finding novel molecular biomarkers that can be used for diagnosis, prediction, and prognosis.

Highlights on the Effects of Non-Coding RNAs in the Osteonecrosis of the Jaw

“…Regarding the clinical features, earlier research has revealed that most patients at risk are female, have an average age of 65.3 years, and that the mandible is the most often affected jawbone [3,4]. ONJ consists of three stages: (i) Stage 0 does not involve a fistula or exposed bone, it is considered a possible precursor to the disease; odontalgia, maxillary sinus discomfort, jaw pain that may extend to the temporomandibular joint region, and altered feeling in the maxilla and mandibular areas are among the symptoms; there could be movement of a tooth and intraoral or extraoral edema that isn't connected to periodontal disease, such as the absence of formation of new bone in the extraction socket, alterations of the structure of bone, osteosclerosis regions, and thickening of the periodontal ligament [5]; (ii) Stage 1 involves a fistula or exposed necrotic bone without any signs of inflammation; radiographic images may be limited to the alveolar bone region and resemble those of Stage 0; (iii) in Stage 2, patients exhibit symptoms such as an exposed necrotic bone or a fistula, along with signs of infection and inflammation; (iv) Stage 3 is characterized by an exposed and necrotic bone or fistulae that probes the bone, along with infection and pathological fracture, extraoral fistula, oral-antral or oral-nasal communication, osteolysis extending to the inferior border of the mandible or sinus floor, or exposed necrotic bone extending beyond the region of the alveolar bone as complications [6][7][8].…”

“…Angiogenesis inhibition prevents human endothelial cells from adhering to each other and migrating, hence preventing tumor invasion and metastases. Another theory, based on initial findings on animals, recognizes the central role of inflammation and infection, since after the sick teeth were extracted from animals receiving antiresorptive medication, the animals displayed poor healing, including mucosal abnormalities, significant inflammatory infiltrates in the sockets, bone exposure and osteonecrosis zones [6] (Figure 1).…”

“…In fact, keratinocytes were prevented from finishing their cell cycles during cell proliferation, and fibroblasts underwent apoptosis. Furthermore, in ONJ human biopsy tissue, it was found that delayed periodontal repair was associated with altered transforming growth factor beta 1 (TGFβ1) signaling [6].…”

“…MiRNA microarray investigation revealed that 44 miRNAs were downregulated and 49 miRNAs were upregulated throughout the early, middle, and late phases of murine osteoclastogenesis (Table 1) [15]; miR-29, miR-31-5p, hsa-miR-422a, hsa-miR-148a-3p, miR-183-5p, miR-214-3p, and miR-9718 were found to be expressed in a way that promoted osteoclastogenesis, while miR-7b-5p, miR-26a-5p, miR-34a-5p, miR-124-3p, miR-125a-5p, miR-146a-5p, miR-218-5p, and miR-503-5p were found to be expressed in a way that inhibited osteoclastogenesis. Furthermore, three miRNAs-miR-21-5p, hsa-miR-133a-3p, and miR-223-3p-were demonstrated to have both promotion and inhibitory effects [6]. In a recent study, patients with multiple myeloma and with or without ONJ had their miRNA levels examined and it was demonstrated that miRNAs miR-16-1, miR-21, miR-23a, miR-28, miR-101-1, miR-124-1, miR-129, miR-139, miR-145, miR-149, miR-202, miR-221, miR-424, and miR-520 were considerably overexpressed in ONJ patients compared to controls.…”

High-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries

“…Correlation of age to methylation. It is well established that human aging is associated with characteristic changes in DNA methylation throughout the genome [32][33][34]. To estimate the size of this effect in our markers, we t linear regression models between age and DNA methylation level (Additional le 1: Fig.…”