Aging is a process of intrinsic decline that should be distinguished from damage induced by external causes, such as accidents, radiation, or predation. A system that ages typically exists far from equilibrium. Aging is a process that makes a complex system more likely to fail the longer it has been in existence. This is in stark contrast to the radioactive decay of, say, plutonium into uranium, which does not depend on how long an atom of plutonium has been around.
Most forms of life have repair mechanisms, such as molecular machines that repair genes or stem cells that regenerate tissues or chaperones that assist in restoring protein folds. The aging of living systems is therefore particularly interesting, since it occurs despite sophisticated forms of repair. This raises the question whether animals can live much longer than they actually do, even under ideal conditions. Could they, in principle, live forever?
Repair systems are imperfect. They too get damaged and decline in efficacy. Does physics set an upper limit to how long any living system can maintain itself? How is maximal lifespan linked to the organizational structures that distinguish different forms of life? Is aging in plants different from aging in animals? Is aging inescapably built into the logic of life?
Biological life spans are highly variable across species. For example, the life spans of mammalian species range from less than a year for a shrew to 200 years for some whales. Life spans also vary considerably within each species, reflecting a diversity of genetic backgrounds across individuals. We all know friends or relatives that are long-lived, while others seem to age more rapidly. Yet, even genetically identical individuals, such as laboratory populations of the nematode C.elegans, exhibit a large variation in lifespan. This fact emphasizes the random nature of the aging process. Individuals that start out with the same genetic endowment accumulate random damage that becomes either irreparable or too costly to repair given the many other tasks an organism must fulfill to get by. What are the sources of molecular damage internal to an organism? Which type of damage is most detrimental? Since damage affects the consequences of subsequent damage, we are led to wonder how much the process of aging plays out in a unique way for each individual and how much of that process is governed by regularities. Life spans not only exhibit variation, but they also seem quite malleable by environmental and genetic interventions. For example, genetic mutations in the worm C.elegans can result in a tenfold extension of lifespan. Researchers are intensely studying the processes that are affected by these mutations.
While damage may be random, its consequences are not. The consequences of random damage reflect the organizational structure of an organism. The study of aging thus stands in a certain analogy to the study of evolution. In aging, genetic change occurs throughout the lifetime of an individual in the cells that make up its body. In evolution, genetic change occurs across generations in the cells that make up the heritable germ line. In both cases, mutations or damage are random, but their consequences are not. Absent a distinction between body and germ line, as in the case of bacteria, aging and evolution begin to blend.
During the process of evolution, detrimental mutations within a population of individuals are selected against, while non-detrimental mutations pave the way towards phenotypic innovation. In the process of aging, mutations occur within the population of cells that constitute our bodies, potentially disrupting their coordinated and cooperative behavior. The forms and consequences of such disruption may reflect the ancestral conflicts between cells that had to be resolved by evolution to stabilize a multicellular organization. Cancer reminds us that the specialized cells of our bodies were once autonomous entities. Studying how an organism falls apart offers insights into how it has been put together by evolution and how it is assembled in development.
While aging is of fundamental interest to biology, in particular as it pertains to us humans, it is not a phenomenon limited to life. Complex materials that exist or operate far from equilibrium wear out. Rubber, glass, and steel, age. Nuclear weapons age, and so does our planet. Physicists think of aging as the progressive inability of a material to forget a disturbance or to maintain memory of a reference state. With age, a complex material, like a mattress, loses the capacity of returning to an original state. Likewise, the progressive loss of the cognitive capacity known as human memory might be seen as the increasing failure of an aging neurological system to return to an original state of mental identity. Cognitive systems are subject to aging, and so are cultures. Institutions, such as universities, firms, markets, and nations are aging. Cities age. Perhaps even the universe is aging. Everything organized seems to age.
Even if aging were ultimately but a process of “wearing out” – some approach to equilibrium – the study of aging is not driven by an interest in its end point. Rather, it is motivated by the need to understand the idiosyncratic dynamical trajectories that this intrinsic “wearing out” assumes, that is, the phenotypes of failing (not just of failure) and their consequences for evolution and ecosystems. If we desire to become better stewards – doctors, CEOs, political leaders, engineers – of natural and human-made organizations, we must understand how such organizations age and how aging is connected to change and evolution.
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