The current standard treatments for cancer, chemotherapy and radiotherapy, are quite unpleasant and harmful; no-one would voluntarily undergo them given a better alternative. In fact, treatment makes people physically older, accelerating the processes of aging. There is evidence to suggest that this is due to an added burden of senescent cells. Cells become senescent in response to damage or a toxic environment, and there is plenty of that going around in any earnest attempt to treat cancer with radiation or chemical agents; in fact, many cancer therapies are intended to aggressively induce senescence in tumor cells.
The presence of senescent cells is one of the causes of aging. These cells remove themselves from the usual cycle of replication, and in normal circumstances near all self-destruct or are destroyed by the immune system. Unfortunately, enough linger to contribute to aging. They produce harm through inflammatory signaling, the senescence-associated secretory phenotype (SASP), that corrodes tissue structure and disrupts tissue function - insignificant in small amounts, but very damaging given a sizable number of such cells. There are no doubt other mechanisms by which present cancer therapies touch on the causes of aging, however; given that aging is damage, and cancer treatments are damaging in many ways, we should probably not be surprised to find that aging is accelerated.
Studies among long-term cancer survivors indicate numerous possible clinical complications resulting in considerable morbidity and mortality, related to chemotherapy, radiation therapy, or both. A wealth of observational data on the development of late complications in cancer survivors are available, but information documenting the pathological basis for development of these effects is sparse. To understand the biology of late effects better and provide a foundation for the development of interventions, it is important to characterise late effects at the cellular level. Cancer survivors, in general, appear to develop age-related diseases and phenotypes sooner than members of the general population. This is likely because damage to normal tissues from cancer therapies diminishes physiological reserve, accelerates processes typically associated with ageing, or both.
The roles of telomeres, senescent cells, epigenetic modifications, and microRNA have been described in terms of their contributions to the pathobiology of accelerated ageing. However, published data linking clinical phenotypes seen in cancer survivors with processes of accelerated ageing at the cellular level is lacking. On a microscopic level, ageing is a consequence of gradual, lifelong accumulation of molecular and cellular damage and loss of physiological integrity. Hallmarks of ageing include genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, chronic low-grade inflammation, and cellular senescence. We have demonstrated with clinical data that cancer survivors develop the health-related manifestations of ageing more quickly than their peers. While ageing prematurely is a better alternative to dying prematurely, a better understanding of what drives this process presents an opportunity for improvement.
As many cancer treatments appear to induce an accelerated ageing-like state, interventions that target fundamental ageing processes may have a role in cancer survivors. Since many cancer therapies induce cellular senescence, among the most promising agents are senolytics, drugs that selectively eliminate senescent cells and SASP inhibitors, which blunt local and systemic effects of the SASP. These agents alleviate frailty, restore progenitor function, reduce insulin resistance, rescue cardiac and vascular dysfunction, decrease adverse effects of radiotherapy and reduce osteoporosis in a variety of animal models of ageing and disease. Senolytics are effective when administered intermittently, potentially reducing toxicity, and resistance to these drugs is unlikely to develop as, unlike cancer cells or microbes, senescent cells do not divide.