美国近85%的癌症死亡发生在60岁或以上的人群中，近30%的癌症死亡发生在80岁或以上的人群中。为何癌症（尤其是危及生命的癌症）与衰老如此紧密相关呢？
最常见的癌症源于细胞和组织，其中细胞的持续更新和补充对健康的身体功能至关重要。为了产生新细胞，基因组DNA（全部60亿个碱基对）必须准确无误地复制，这是一项几乎不可能达成的任务。有少数错误不可避免地逃脱了用于保障DNA复制的校对和修复过程，随着时间的推移导致突变的积累。当新生的细胞暴露于致癌物（如烟草烟雾中的致癌物）或活性氧（含氧的不稳定分子，与包括癌症在内的多种疾病有关）时，也可能导致突变的积累。
William G. Nelson博士
伴随着这些新生细胞的基因组受到的残酷威胁，随着年龄的增长，导致关键基因缺陷并将正常细胞转化为癌细胞的基因突变发生的概率也预计会增加。有一种现象可以支持这一观点，那就是具有遗传性DNA修复缺陷因而导致大量突变的人往往在较年轻时就患上了癌症。
最近的研究聚焦衰老对外观正常的细胞的影响（这些细胞为癌细胞提供基础结构支持）。癌细胞通常需要附近细胞的帮助，来重塑癌细胞的生长环境，通过形成新的血管为癌细胞创造营养和氧气的供应链，并确保癌细胞能够逃避或抑制可能摧毁它们的免疫反应。
Exploring the Connection Between Cancer and Aging
By Cancer Today Staff
Guest Post by William G. Nelson, MD, PhD, Editor-in-Chief, Cancer Today
Nearly 85 percent of all cancer deaths in the U.S. occur in men and women 60 or older; almost 30 percent of cancer deaths occur in people 80 or older. Why are cancers, particularly life-threatening ones, so tightly associated with aging?
The most common cancers arise from cells and tissues where ongoing renewal and replenishment of cells are essential for healthy body functions. To create new cells, genomic DNA—all 6 billion base pairs—must be copied with no errors, an all but impossible task. Inevitably, a handful of mistakes escape the proofreading and repair processes safeguarding DNA replication, leading to mutations that can accumulate as years go by. Mutations can also accumulate as renewing cells are exposed to cancer-causing chemicals called carcinogens, such as those in tobacco smoke, or to reactive oxygen species, which are unstable molecules containing oxygen that are associated with a variety of disorders, including cancer.
William G. Nelson, MD, PhD
With these relentless threats to the genomes of renewing cells, advancing age would be expected to increase the probability of a mutation leading to a defect in a critical gene and transforming a normal cell into a cancer cell. In support of this notion, people with inherited DNA repair defects that lead to greater numbers of mutations often develop cancers at younger ages.
Recent research has focused on the impact of aging on normal-appearing cells that provide infrastructure support to cancer cells. Cancer cells often require help from nearby cells to help remodel the landscape that serves as home to cancer cells, create a supply chain of nutrients and oxygen for the cancer cells via the formation of new blood vessels, and ensure that cancer cells can evade or suppress immune responses that might destroy them.
The normal cells that assist cancer cells may show the most dramatic effects of age. Some of the same stressors that create cancer cells can inflict cell and genome damage in noncancerous cells in the neighborhood. Rather than become cancer cells themselves when damaged, however, the infrastructure cells often display hallmarks of senescence, a state in which cells can no longer reproduce but can corrupt surrounding cells, influencing their metabolism and promoting the most malignant cancer behaviors.
The phenomenon of cellular senescence has become a major focus of aging research. An accumulation of senescent cells in many organs and tissues may be a significant driver of frailty associated with aging. In animal models, elimination of senescent cells appears to attenuate age-related changes. With these compelling observations, senolytic drugs able to eradicate senescent cells have been working their way into human clinical trials for a variety of age-related conditions.
Can senolytic drugs find a role in cancer treatment? Researchers are examining several scenarios. First to be evaluated may be infrastructure cell senescence triggered by cancer treatment itself, specifically radiation therapy and chemotherapy that might drive normal cells into senescence, undermining cancer control and promoting frailty among cancer survivors. The administration of senolytic drugs along with conventional cancer treatments could improve treatment outcomes and reduce nagging side effects that can compromise cancer survivorship. Senolytic drugs administered with immunotherapy could improve immune responses to cancers. Finally, if senolytic drugs can disrupt cancer metastasis, they might be used alongside surgery and other local cancer treatments to prevent cancer from spreading.
William G. Nelson, MD, PhD, is the editor-in-chief of Cancer Today, the quarterly magazine for cancer patients, survivors, and caregivers published by the American Association for Cancer Research. Nelson is the Marion I. Knott professor of oncology and director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore. You can read his complete column in the fall 2022 issue of Cancer Today.
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