Since the dawn of human consciousness, we have contemplated our own mortality and dreamed of ways of overcoming it. Until recently, achieving control over our own longevity was the stuff of fairy tales, disconnected from actual scientific progress. But new research suggests that the molecular basis of aging may soon be understood in detail. Applying this knowledge could be close behind.
Recent scientific breakthroughs have come from research not on humans, or even on rats and mice, but on simple laboratory organisms like yeast and roundworms. These primitive life forms have yielded important, generally valid clues that have forced a comprehensive re-evaluation of the nature of the aging process.
Traditional evolutionary thought views aging as a process that occurs by default in the post-reproductive phase of life. After all, Darwinian natural selection cannot prevent the wholesale decline of an individual whose genes have already been passed on to the next generation. According to this view, many cellular and organic processes thus degrade concurrently, and aging has many causes. As a result, the post-reproductive shortcomings of a great many genes would have to be remedied to slow the aging process.
Recent research on yeast and roundworms suggests otherwise. It turns out that mutations even in single genes can lead to a substantial lengthening of life span and an accompanying slowdown in the aging process.
But how can this be possible if aging has many concurrent causes, as evolutionary theory maintains?
The answer can be found by examining the molecules that make up the genes in which mutations extend life span. For example, a universal gene called SIR2 determines the life span of both yeast cells and roundworms. In both organisms, if an extra copy of SIR2 is added by genetic intervention, the life span is extended. Conversely, if the SIR2 gene is deleted, the life span is shortened.
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In both yeast and worms, SIR2 appears to sense the availability of food and stall the aging process in times of deprivation by stimulating the formation of specialized body types--spores in yeast and dauers in worms--that can survive for extraordinarily long periods without nutrition. When conditions improve, the dormant life forms revive and reproduce. The survival function that SIR2 exists to serve--forestalling aging and reproduction during famine--is adaptive and therefore pervasive in nature.
So the classical evolutionary theory of aging must be modified. In times of plenty, the aging process plays out as evolutionary biologists say, with reproduction followed by the failure of many genes and a wholesale decline of individual organisms. But in times of scarcity, the survival program kicks in to slow the aging process. Even more intriguingly, a single gene can promote this survival mechanism across a wide swath of nature's creatures.
Does SIR2 also promote survival in mammals? Interestingly, in cultured mouse or human cells, the mammalian SIR2 gene determines a cell's response to DNA damage. When faced with damaging agents, cells have the ability to commit suicide. The mammalian SIR2 gene modulates this process, and higher levels of it dampen the cell death response. Just like in yeast and worms, mammalian SIR2 promotes survival, in this case of cultured cells.
Does this mean that mammalian aging is at least partly caused by the gradual loss of cells and the accompanying failure of organs? Possibly, but we must bear in mind that the cell death response is a way to cull genetically damaged cells before they progress into tumors. So increasing SIR2 activity in mammals may actually cause cancer by keeping bad cells alive too long.
Yet this seems unlikely for two reasons. First, as an evolutionary matter, it makes little sense that a gene anointed by nature to promote survival would also cause cancer. Second, recent experiments in genetically altered mice show that the cell death response may be slowed without causing cancer. This suggests that there is a window of slowing cell death that does not cause cancer and may promote longevity.
Obviously, the practical implications of these findings could prove extraordinary. If single genes can determine the life span of mammals, it should be possible to develop drugs that bind to these genes' proteins and alter their activities. Thus, drugs that slow the aging process could be around the corner.
But will such drugs prolong youth and vitality, or simply extend our stay in nursing homes?
To answer this question, consider the effects of calorie restriction, which has been found to increase life span in organisms ranging from yeast to mammals. In yeast, where the process has been studied in molecular detail, the longevity triggered by calorie restriction is mediated by SIR2. In mammals, we have not yet discovered the molecular basis of the longevity. But we do know that restricted animals are vigorous and healthy for the duration of their longer lives.
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Since the dawn of human consciousness, we have contemplated our own mortality and dreamed of ways of overcoming it. Until recently, achieving control over our own longevity was the stuff of fairy tales, disconnected from actual scientific progress. But new research suggests that the molecular basis of aging may soon be understood in detail. Applying this knowledge could be close behind.
Recent scientific breakthroughs have come from research not on humans, or even on rats and mice, but on simple laboratory organisms like yeast and roundworms. These primitive life forms have yielded important, generally valid clues that have forced a comprehensive re-evaluation of the nature of the aging process.
Traditional evolutionary thought views aging as a process that occurs by default in the post-reproductive phase of life. After all, Darwinian natural selection cannot prevent the wholesale decline of an individual whose genes have already been passed on to the next generation. According to this view, many cellular and organic processes thus degrade concurrently, and aging has many causes. As a result, the post-reproductive shortcomings of a great many genes would have to be remedied to slow the aging process.
Recent research on yeast and roundworms suggests otherwise. It turns out that mutations even in single genes can lead to a substantial lengthening of life span and an accompanying slowdown in the aging process.
But how can this be possible if aging has many concurrent causes, as evolutionary theory maintains?
The answer can be found by examining the molecules that make up the genes in which mutations extend life span. For example, a universal gene called SIR2 determines the life span of both yeast cells and roundworms. In both organisms, if an extra copy of SIR2 is added by genetic intervention, the life span is extended. Conversely, if the SIR2 gene is deleted, the life span is shortened.
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In both yeast and worms, SIR2 appears to sense the availability of food and stall the aging process in times of deprivation by stimulating the formation of specialized body types--spores in yeast and dauers in worms--that can survive for extraordinarily long periods without nutrition. When conditions improve, the dormant life forms revive and reproduce. The survival function that SIR2 exists to serve--forestalling aging and reproduction during famine--is adaptive and therefore pervasive in nature.
So the classical evolutionary theory of aging must be modified. In times of plenty, the aging process plays out as evolutionary biologists say, with reproduction followed by the failure of many genes and a wholesale decline of individual organisms. But in times of scarcity, the survival program kicks in to slow the aging process. Even more intriguingly, a single gene can promote this survival mechanism across a wide swath of nature's creatures.
Does SIR2 also promote survival in mammals? Interestingly, in cultured mouse or human cells, the mammalian SIR2 gene determines a cell's response to DNA damage. When faced with damaging agents, cells have the ability to commit suicide. The mammalian SIR2 gene modulates this process, and higher levels of it dampen the cell death response. Just like in yeast and worms, mammalian SIR2 promotes survival, in this case of cultured cells.
Does this mean that mammalian aging is at least partly caused by the gradual loss of cells and the accompanying failure of organs? Possibly, but we must bear in mind that the cell death response is a way to cull genetically damaged cells before they progress into tumors. So increasing SIR2 activity in mammals may actually cause cancer by keeping bad cells alive too long.
Yet this seems unlikely for two reasons. First, as an evolutionary matter, it makes little sense that a gene anointed by nature to promote survival would also cause cancer. Second, recent experiments in genetically altered mice show that the cell death response may be slowed without causing cancer. This suggests that there is a window of slowing cell death that does not cause cancer and may promote longevity.
Obviously, the practical implications of these findings could prove extraordinary. If single genes can determine the life span of mammals, it should be possible to develop drugs that bind to these genes' proteins and alter their activities. Thus, drugs that slow the aging process could be around the corner.
But will such drugs prolong youth and vitality, or simply extend our stay in nursing homes?
To answer this question, consider the effects of calorie restriction, which has been found to increase life span in organisms ranging from yeast to mammals. In yeast, where the process has been studied in molecular detail, the longevity triggered by calorie restriction is mediated by SIR2. In mammals, we have not yet discovered the molecular basis of the longevity. But we do know that restricted animals are vigorous and healthy for the duration of their longer lives.