Aging and cancer最新文献

The gut microbiome changes with age and affects regions beyond the gut, including the ovarian cancer tumor microenvironment. In this review summarizing the literature on the gut microbiome in ovarian cancer and in aging, we note trends in the microbiota composition common to both phenomena and trends that are distinctly opposite. Both ovarian cancer and aging are characterized by an increase in proinflammatory bacterial species, particularly those belonging to phylum Proteobacteria and genus Escherichia, and a decrease in short-chain fatty acid producers, particularly those in Clostridium cluster XIVa (family Lachnospiraceae) and the Actinobacteria genus Bifidobacterium. However, although beneficial bacteria from family Porphyromonadaceae and genus Akkermansia tend to increase with normal, healthy aging, these bacteria tend to decrease in ovarian cancer, similar to what is observed in obesity or unhealthy aging. We also note a lack in the current literature of research demonstrating causal relationships between the gut microbiome and ovarian cancer outcomes and research on the gut microbiome in ovarian cancer in the context of aging, both of which could lead to improvements to ovarian cancer diagnosis and treatment.

Ion gradients across cell membranes generate voltage potentials that are involved in a wide range of biological processes. According to the membrane hypothesis of aging, aging is inextricably linked to a decrease in resting membrane potential (V_mem). Alterations in ion channel activity and membrane fluidity caused by aging disrupt bioelectric homeostasis, increase intracellular calcium and potassium concentrations, induce abnormal mechanistic target of rapamycin (MTOR)- and AMPK-regulated metabolism and energy dissipation, and decrease proliferation and regeneration. Failure to maintain ion channel activity and membrane potential leads to cell senescence or death. There is evidence that by manipulating ion channel activities, a cryptic memory can be recalled to restore lost proliferative or regenerative abilities. Reversal or prevention of senescence, aging phenotypes, and longevity may be achieved by fine-tuning mitochondrial membrane polarization. Therefore, there is optimism that deciphering the bioelectric codes that govern cell functions will lead to the development of new gero-electroceuticals that restore cell function and prevent tissue loss during aging.

Aging and cancer are increasingly becoming big challenges for public health worldwide due to increased human life expectancy. Meanwhile, aging is one of the major risk factors for cancer. In December 2019, the first International Conference on Aging and Cancer was held in Haikou, Hainan province (island), China, preluding the establishment of the International Center for Aging and Cancer (ICAC) at Hainan, an institute dedicated to the research at the intersection of aging and cancer. Since then, the ICAC has hosted the annual conference each December in Hainan. The 2022 ICAC conference, with the theme of “promoting longevity with less cancer,” invited 17 internationally renowned scientists to share their new research and insights. Topics included DNA methylation in rejuvenation, development, and cellular senescence; lifespan regulation and longevity manipulation; metabolism and aging; cellular senescence and diseases; and novel therapeutics for cancer and antiaging/anticancer drug discovery. The forum highlighted the interconnectedness of aging and senescence with cancer evolution and risk. Although there is hope for preventing diseases like cancer by modulating systems that also control lifespan, attention has to be paid to the conflicting needs and competing demands in human biology.

Methods to detect cellular senescence have become increasingly important, even more so in living animals and humans. This cellular state has been found to play fundamental roles in physiological processes as well as functioning detrimentally toward the advent or progression of pathological conditions. Importantly, the study of senescence involvement in these processes in vivo cannot be done without living-friendly technologies enabling senescence detection. Furthermore, senotherapies or therapies that selectively kill senescent cells have emerged as a new therapeutic strategy for aging and age-related diseases such as atherosclerosis, cancer, and neurodegenerative disorders and require tools to evaluate their use in vivo. As of now, our in vivo senescence detection toolkit includes genetically engineered reporter mouse models and small molecule imaging probes. Herein, we will focus on the detection of senescence in vivo, including a summary of its challenges, current detection methods and strategies, and a perspective on overcoming the current obstacles.

Prior to the past few years, the development of new therapies for acute myeloid leukemia (AML) has been disappointingly slow. For several decades, the standard therapy for AML has consisted of intensive induction chemotherapy, and potentially a subsequent hematopoietic stem cell transplant. Unfortunately, older patients are less responsive to, and are frequently unfit to tolerate, such intensive chemotherapy. Given that a majority of AML patients are elderly, this population has been most affected by the lack of newer less toxic therapies. However, in recent years, the treatment landscape for AML has dramatically shifted with the approval of many new drugs. As summarized in this review, several of these new drugs are targeted agents that are better tolerated than standard chemotherapy and could substantially benefit elderly patients. Although drug resistance remains a major concern, the treatment options for elderly AML patients are more numerous than ever before, bringing new promise for improved patient outcomes.