There are all these people who say that death is natural, it’s just part of life, and I think that nothing can be further from the truth,” Peter Thiel told Business Insider in 2012. The venture capitalist has spent years backing efforts to slow or defeat aging, and his provocation captures the confidence of a wider Silicon Valley project: Given enough money and biological engineering, death may become just another technical problem to solve.

Nature, it seems, remains wholly uninspired by Silicon Valley capital. Scientific insight into 3.5 billion years of evolution suggests that death isn’t a glitch—it’s working as intended. That does not mean every organism carries a simple genetic suicide switch, or that every death is adaptive. It simply means that natural selection favors reproductive success over immortality. It also explains aging as the ultimate compromise for a body balancing the competing energetic requirements of development, reproduction, and repair.

“There is a cost to living, a cost to doing everything” Nick Lane, a biochemist at University College London, told Philip Ball in an interview with Nautilus. Lane examines life through the lens of energetics. He studies how much energy is required for life’s various processes, and how organisms go about acquiring and spending it.

“If we are living our lives at a very fast rate, we tend to, in effect, wear out sooner,” Lane said. Living is strenuous work. Growth, mating, pregnancy, parental care, and immune defense all consume energy and take a physical toll. Because maintenance and repair are themselves energetically costly, they must be traded off against these processes.

Read more: “The Immortality Hype”

Across the animal kingdom, species have evolved different ways of allocating energy throughout their lives, mostly according to their size and exposure to external hazards. One consequence of this is that animals have vastly different natural lifespans.

Consider the mouse and the elephant. In the wild, a field mouse can live up to two years, whereas an elephant can live to 70. But mice are small and die easily, from predators or harsh weather. In such easy prey, natural selection is highly skewed toward early reproduction. An expensive body maintenance program for a distant (and highly unlikely) old age makes no sense. For an elephant, which matures slowly and faces fewer predators, evolution has selected for a durable body and a longer lifespan.

Overall, smaller species live fast lives, reproduce early, and die young. “There is a very strong relationship between metabolic rate, the rate at which we’re taking in oxygen and burning up food, and lifespan,” Lane said. This may help explain, at least partially, why caloric restriction can double or treble the lifespan of very simple organisms, like worms or fruit flies. Without calories, reproduction is unlikely and organisms enter a phase of “battening down the hatches and waiting out the bad times,” Lane said. But humans, of course, are far more complex. Our bodies are finely tuned to run at a metabolic rate held within narrow limits. Simply restricting calories in our diet would lead our bodies to burn up protein in muscle and other tissues.

In fact, humans are unusually long-lived for primates of our size. “Given our body mass, we live about twice as long [as we should for our size],” Venki Ramakrishnan, the Nobel Prize-winning structural biologist and author of Why We Die, told me. Improvements in nutrition, sanitation, and medicine have doubled the average human lifespan over the past 150 years, but our longevity has deeper roots. Michelangelo, Ramakrishnan noted, lived to nearly 90 in the 16th century, and some researchers believe human lifespans began lengthening as far back as 40,000 years ago. The drivers for the change remain unclear, Ramakrishnan said. A leading hypothesis links a sudden shift in human lifespan to the evolutionary perks of having grandparents in hunter-gatherer communities. Older adults helped raise children while parents were busy providing food. In times of crises, their accumulated knowledge of the environment gave their tribe a decisive edge in survival.

Given that modern humans have escaped many of the hazards that once made longevity a poor evolutionary investment, and that leaps in lifespan are possible, it makes sense to wonder if perhaps the billionaires have a case. Or, as Ramakrishnan put it, “The real question is, we have mechanisms for repairing damage, so why don’t we just keep repairing our body and live forever?”

The answer cuts to the heart of aging research.

Even in the absence of multiple stressors—we live comfortable lives indoors sheltered from environmental extremes and carry a significantly lower pathogen load than our ancestors—our bodies have evolved to keep the time. In 2022, Steve Horvath, a professor at the University of California, Los Angeles and a leading figure in anti-aging research, uncovered the existence of a molecular clock, a universal, internal mechanism that marks the age of mammalian cells and tissues. It reveals that aging is neither entirely random nor simply the accumulation of visible wear.

Throughout a cell’s life, patterns of chemical tags on DNA (called epigenetic markers) accumulate. Horvath developed a formula that reliably deciphers the pattern to predict the age of cells and tissues. This pattern is the “biological” age of the cell, which closely aligns with, but doesn’t always precisely map, chronological age. Its accuracy (for humans, it is exact to plus or minus 3.6 years) implies that aging is a carefully maintained biological process, rather than a haphazard set of events. We speed up the clock with things like smoking and excessive alcohol consumption.

Some scientists interpreted Horvath’s discovery—that all tissues count time—as indication that we are programmed to die, our cells marching inexorably toward death. But Horvath’s own interpretation swerves clear of such determinism and focuses instead on what the clock achieves in our early years.

We don’t think of babies as aging, but that is when the aging program is most active. Embryonic cells (which start off identical) need to differentiate quickly and in perfect synchrony into tissues, building organs and a body that continues to mature into adulthood. An internal metronome serves the essential function of orchestrating the elaborate process. But after adulthood, the program continues to run, and runs us all the way to the ground. “Evolution did not select a program that makes us die,” Horvath said. Instead, “Mother Nature never selected against it.”

As Ramakrishnan told me, “Death is an unintended consequence of aging.” And aging is an unintended consequence of development. Research shows that once development is complete (once we reach reproductive age), some of the genetic machinery that enabled it can keep running, or become reactivated as its regulation deteriorates, with increasingly harmful effects. In old mice, for example, the gene Hoxa9, which is essential to a developing embryo, switched back on in muscle stem cells, activating obsolete developmental pathways that hindered muscle repair.

One of the hallmarks of aging is cellular senescence. It is a state in which damaged or stressed cells permanently stop dividing yet resist dying, accumulating in tissues over time. Though senescence initially protects against cancer by halting the growth of compromised cells, senescent cells secrete inflammatory molecules that harm surrounding tissue and drive many features of aging.

The runaway developmental programs of old age stem from the same evolutionary trade-off that links metabolism to lifespans. Selection prioritizes early biological performance (the period before reproduction happens) over late-life durability. A gene that promotes development or improves fertility and survival at 20 can be favored even if it raises the risk of degeneration at 70. A defect expressed only at 90 will encounter limited evolutionary pressure. Death is a compounding of the problem across a genome composed of genes all acting under the same selection. It is the final bill for evolution’s early favors.

All of this makes anti-aging innovations extremely challenging. Roughly 2,000 master control genes orchestrate early embryonic development, supported by another 5,000 to 10,000 organ-building genes. Re-tuning them for longevity without wreaking havoc is well beyond our current capabilities. “I don’t think it’s an impossibility, but it’s incredibly difficult,” Ramakrishnan told me.

The most immediate threat of getting this balance wrong is cancer. That’s because the signaling pathways that encourage cells to divide and repair tissues in early life are the exact same pathways that tumors hijack to proliferate unchecked. Override those aging pathways, and you remove the guards keeping malignancy at bay.

Researchers have already encountered this trade-off in one of the best-studied longevity pathways, which involves growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Because IGF-1 promotes cell growth, muscle maintenance, and tissue repair, boosting its activity once seemed a plausible anti-aging strategy.

Read more: “Physics Makes Aging Inevitable, Not Biology”

But the same signals that encourage healthy cells to regenerate can also encourage precancerous cells to survive and multiply. Animal studies consistently show that reducing GH and IGF-1 signaling extends lifespan while lowering cancer incidence, whereas chronically elevated IGF-1 activity is associated with an increased risk of several cancers. The pathway that helps build and maintain the body in youth can become a liability when kept active into old age.

This compromise should not be entirely surprising. Adult stem cells possess an unusual capacity for long-term self-renewal, while cancer cells achieve essentially limitless proliferation by escaping the body’s normal controls. Efforts to make ordinary cells more regenerative inevitably edge them toward the biology of tumors. “An organism doesn’t want cells capable of indefinite reproduction,” Ramakrishnan said, “because that’s a cancer risk. You can think of senescence as evolution’s way of preventing cancer.”

The pattern is becoming uncannily familiar throughout aging biology: Molecules and pathways once cast as villains often turn out to have essential functions. For decades, scientists believed that aging was largely driven by the accumulation of damage from reactive oxygen molecules, or free radicals, produced by mitochondria. The theory was so influential that antioxidant supplements were widely promoted to slow aging. But decades of research have failed to support that idea.

Large clinical studies found little evidence that high-dose antioxidant supplements extend life or prevent age-related disease, and some have even linked them to worse outcomes. Rather than being merely destructive, Lane explained, free radicals act as vital cellular signals. “They are behaving a little bit like the smoke detector,” he said. When cells detect those signals, they activate genetic programs that repair damage, strengthen stress resistance, and help the cell survive. Blunting that signal indiscriminately is counterproductive. “The trouble with antioxidants is they’re in effect disabling the smoke detector,” Lane said.

A similar paradox occurs with anti-aging therapies that target the inflammatory response. Inflammation is essential for healing and immunity, but with age, damaged and senescent cells can keep the immune system locked in a state of chronic low-grade activation. Persistent inflammation, which longevity scientists have dubbed “inflammaging” has been linked to increased risk of diabetes, Alzheimer’s, and cardiovascular diseases.

In 2017, a Novartis trial of more than 10,000 heart attack survivors showed that canakinumab, an antibody that blocks a single inflammatory molecule, successfully cut the risk of further cardiovascular events, all without touching cholesterol. At first this was touted as progress in the fight against inflammaging. But ultimately the Food and Drug Administration declined to approve the use of canakinumab in any setting. The agency deemed that the risk of developing severe infections, which had been observed in some of the trial participants, was too high. The trial served to add further proof that the inflammatory response has evolved for good reason.

Eric Topol’s 2025 book, Super Agers, offers a discerning look at longevity medicine. The cardiologist and scientist argues that rather than chase immortality, our focus should be to extend “healthspan” by preventing or delaying the major diseases of aging, such as cancer and Alzheimer’s. Better risk prediction, vaccines, exercise, sleep, nutrition, and earlier treatment could all reduce the years people spend with disease. This would make for a scientifically serious agenda, precisely because it does not require fighting millions of years of evolution. The most plausible successes would compress morbidity, with more years of strength and independence. Even modest gains would matter enormously.

Ramakrishnan likewise sees life extension beyond the apparent human limit as an extreme and selfish undertaking by the world’s richest technocrats. “It’s just fantasies at this point, and a distraction from our real problems,” he told me. “It’s the same group of people who are touting space travel and colonization as some big hope for humanity, while ignoring all the real problems on Earth, like climate change, disease, and having enough water to drink.”

Thiel was right in one narrow sense: We should not mistake the natural for the inevitable. Nature gives us challenges and it is part of being human to strive against them. But declaring death unnatural does not make it so; it mistakes defiance for evidence. Immortality evangelists believe enough intelligence and capital can free us from the evolutionary constraints that have governed every biological lineage on Earth. Their resources may help science understand aging and extend healthy lives, but evolution has already delivered a verdict on the larger boast: Life persists. Individual bodies do not.

Lead image: Tasnuva elahi; with images by ImageFlow and alex / Adobe Stock