Читать книгу Aging - Harry R. Moody - Страница 30

Normal aging is not a disease but instead denotes a series of progressive changes associated with increasing risk of mortality. But not all age-related changes involve mortality. For example, hair often turns gray with advancing age, but hair color does not diminish survival prospects. By contrast, other progressive changes lead to losses in functional capacity or the ability of biological structures to perform their proper jobs. For example, as blood vessels age, they tend to lose elasticity, a tendency known as arteriosclerosis or hardening of the arteries. Over time, arteriosclerosis can increase the likelihood of blockage and therefore the risk of damage that we describe as stroke or heart attack.

At the biological level, aging seems to result from changes taking place at the level of molecules, cells, tissues, and the whole organism. How do we recognize such changes? The simplest way to study the effects of aging at these levels is to compare younger and older organisms and note the differences. Such studies employ a cross-sectional methodology; that is, they look at physical function of people at different chronological ages, but at a single point in time. The general conclusion from such studies of human beings suggests that most physiological functions begin to decline after age 30, with some individual variations.

A purely cross-sectional design is not necessarily the best way, however, to measure the changes presumably brought about by biological aging. For one thing, it is difficult to be sure we have taken into account all of the possible variables that might contribute to changes with age in the organism. Thus, a contrasting methodological approach, a longitudinal design, is sometimes used. The same individuals are followed over a long period to measure changes in physical function, or other abilities, at different ages. This approach also has problems. For instance, with human beings, we need to consider the influences of a changing external environment. Furthermore, carrying out longitudinal studies is expensive and not easy when the subject is a long-lived organism like a human being. But the results can be of great importance.

One of the most important studies of this kind has been the Baltimore Longitudinal Study of Aging, sponsored by the National Institute on Aging (Shock et al., 1984). In the Baltimore study, scientists looked at 24 distinct physiological functions (Sprott & Roth, 1992). These functions are called biomarkers, or biological indicators that can identify features of the basic process of aging (Shock, 1962). Some of the most commonly measured biomarkers are diastolic and systolic blood pressure and auditory or visual acuity. Others include the ability of the kidney to excrete urine and the behavior of the immune system. All of these biomarkers tend to decline with increases in chronological age (Warner, 2004), but the rate and amount of decline differ between individuals. The search for biomarkers continues, but biologists have failed to find a “magic clock” that would give us definitive measurement of the rate of aging in individuals (Carnes, 2016).

Many age-related changes in physical function have already been documented, some of them familiar. For instance, with increased age, height tends to diminish while weight increases; hair becomes thinner, and skin tends to wrinkle. Another change is the loss in vital capacity, or the maximum breathing capacity of the lungs. With aging, both respiratory and kidney function decrease. But this decline chiefly results in a loss of reserve capacity, or the ability of the body to recover from assaults and withstand peak-load demands, as during physical exertion. Diminished reserve capacity may not have any discernible impact on the normal activities of daily living. For instance, not having reserves to run a marathon race is probably irrelevant to most activities of daily life.

A key finding from studies of biological aging is that chronological age alone is not a good predictor of functional capacity or “biological age.” In other words, people of the same chronological age may differ dramatically in their functional age, which can be measured by biomarkers (Anstey, Lord, & Smith, 1996).

Scientists have not yet identified a single overall mechanism that gradually reduces functional capacity. Increasingly, however, they have come to believe that the process of aging is controlled at the most basic level of organic life. The key to reversing the process of aging may lie in the strands of the molecule called DNA (deoxyribonucleic acid), the basis for heredity in living cells. At the same time, we can recognize aging at the levels of cells, tissues, and organ systems, such as the nervous system or circulatory system.

For each species, there appears to be a maximum time, or lifespan, for how long a member of that species can survive. By contrast, life expectancy from birth is the average number of years an individual may be expected to live. Maximum lifespan, in other words, is always higher than average life expectancy. Maximum human lifespan, or longevity, may be determined by biological processes separate and distinct from those that bring about the time-related declines we see as aging. In fact, it might turn out that maximum lifespan is determined by factors much simpler than whatever degrades functional capacity. At this point, it seems likely that longevity is genetically determined. Some scientists have argued that natural selection may have promoted longevity-assurance genes (Olshansky & Carnes, 2002; Sacher, 1978). In other words, evolution may have arranged for us to live as long as we do, but not necessarily for us to have the signs and symptoms of aging that we do.

Medawar (1952) was one of the first to advance the idea that a species might carry harmful genes whose time of onset was delayed until after the period of reproduction. If those same genes had the positive virtue of promoting reproduction, then such genes would be transmitted to future generations. This idea of a trait being beneficial in early life but harmful in later life is known as antagonistic pleiotropy. For example, the disease known as sickle-cell anemia, prevalent in Africa, is genetically linked to resistance to malaria. Those people born with the sickle-cell trait are more likely to survive malaria and pass the gene on to their children. This idea helps explain how diseases and senescence could actually be the product of natural selection through evolution (Williams, 1957).

Much remains to be discovered about genetic links between evolution and longevity. Genes with a favorable influence early in life, perhaps by maintaining reproductive capacity for a longer time, could have a harmful influence later on by allowing individuals to pass on linked genes with a negative impact, such as a shorter lifespan. In contrast, the genes that determine maximum lifespan could turn out to be linked to genetic factors that forestall the degenerative diseases of late life. Thus, under the most favorable scenario, if we were to discover and intervene in the genetic causes of longevity, we might also find the key to reducing the disabilities and dysfunctions of old age.

Scientists studying genetic influences on aging and longevity have moved in a number of suggestive research directions. From an evolutionary point of view, for example, there is no obvious reason that human beings should live beyond 30 or 40 years, which gives them enough time to reproduce. There seems to be a trade-off between the biological investment made in survival for reproduction and maintaining organs and tissues beyond the end of the reproductive period.

In fact, we see from population studies of animals in the wild that aging rarely exists. The sea anemone, for example, seems to exhibit no physiological losses with chronological age at all. Animals in the wild exhibit survival curves similar to those of human populations; that is, most individuals die during a certain age range, but others die when very young or when very old. What follows from this evolutionary argument is that there is no intrinsic biological necessity for aging, and thus no reason why raising the maximum lifespan would be impossible.

According to one optimistic view, most of the decremental changes associated with aging—including potentially preventable diseases, such as Alzheimer’s—are not the result of any preprogrammed, built-in requirement for decline, but are the result of environmental causes (Cutler, 1983). However, maximum lifespan seems to be largely shaped by specific genetic endowment, rather than environmental factors. Perhaps, then, aging is a passive or indirect result of biological processes, whereas maximum lifespan is a positive or direct result of evolution. From this perspective, it follows that both the rate of aging and the maximum lifespan of a species could change—and change relatively quickly.

Some provocative questions follow: Would it be possible by direct intervention to alter the genetic code and thus delay the onset of age-dependent illnesses and perhaps to slow down the rate of aging itself (Austad, 2015)? With deeper biological knowledge, could the maximum lifespan be extended to 150 or 200 years or beyond? Even to ask these questions shows just how far we have come from a traditional view of the human life course, in which birth, aging, and death were facts simply taken for granted as part of the unalterable nature of things (Aaron & Schwartz, 2004; Pew Research Center, 2013).