The demographic and biomedical case for late-life interventions in aging

Abstract

The social and medical costs of the biological aging process are high and will rise rapidly in coming decades, creating an enormous challenge to societies worldwide. In recent decades, researchers have expanded their understanding of the underlying deleterious structural and physiological changes (aging damage) that underlie the progressive functional impairments, declining health, and rising mortality of aging humans and other organisms and have been able to intervene in the process in model organisms, even late in life. To preempt a global aging crisis, we advocate an ambitious global initiative to translate these findings into interventions for aging humans, using three complementary approaches to retard, arrest, and even reverse aging damage, extending and even restoring the period of youthful health and functionality of older people.

Fig. 1. Chronic diseases and aging

The incidence of major chronic diseases rises exponentially with age, as shown: cardiovascular disease (blue squares) [data from (32)], cancer (red diamonds) [data from (32)], AD (gray squares) [data from (33)], and influenza-associated hospitalization (green triangles) [data from (34)]. Incidence rates are normalized to the first data point.

Fig. 2. Postponing degeneration

This illustration compares the trajectories of the proposed modalities of intervention necessary to achieve the target (7) of a 7-year average postponement of the onset of age-related degeneration, depicted in terms of (A) an exponential rise in mortality rates and (B) survival. The black trajectories indicate scenarios if no interventions are applied. Nutritional and other public health interventions would need to be applied aggressively and from an early age (ideally prenatally) (yellow trajectories). Metabolic interventions applied from an early age would suffice even if they only mildly slowed the rate of accumulation of aging damage (purple). Metabolic interventions applied only from middle age would need to at least halve this rate—a daunting challenge (green). Late-onset regenerative therapies would postpone biological aging by substantially reversing the initial level of aging damage and then allowing it to continue as normal, but they would also be challenging to implement comprehensively enough (blue). A combination of more modest implementations of the late-onset metabolic and regenerative approaches seems most tractable and could lead to an equal or greater extension of healthy productive life (red).