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Why We Die

The New Science of Aging and the Quest for Immortality, a book written by Venki Ramakrishnan

A groundbreaking exploration of the science of why and how we age and die—from Nobel Prize-winning molecular biologist Venki Ramakrishnan. The knowledge of death is so terrifying that we live most of our lives in denial of it. Throughout human history—from the immortal afterlife of Judeo-Christian thought to the cycle of reincarnation posited by many Eastern religions—we have developed beliefs that allow us to avoid recognizing its finality. One of the most difficult moments of childhood must be when each of us first realizes that not only we but all our loved ones will die—and there is nothing we can do about it. Or at least, there hasn’t been. Today, we are living through a revolution in biology. Giant strides are being made in understanding why we age—and why some species live longer than others. Could we eventually cheat disease and death and live for a very long time, possibly many times our current lifespan? Venki Ramakrishnan, recipient of the Nobel Prize in Chemistry and former president of the Royal Society, takes us on a riveting journey to the frontiers of biology, asking whether we must be mortal. Covering the recent breakthroughs in scientific research, he examines the cutting edge of efforts to extend lifespan by altering our natural biology. But might death serve a necessary biological purpose? What are the social and ethical costs of attempting to live forever? Why We Die is a narrative of uncommon insight and beauty from one of our leading public intellectuals.

Why We Die Book Review

If you're looking for an indepth introduction to longevity research, which isn't just the usual healthy lifestyle tips, then this could be it. Venki Ramakrishnan may be an outsider when it comes to ageing research, but he was president of the Royal Society between 2015 and 2020 and won a Nobel Prize in 2009 for research on the structure and function of ribosomes - so he is definitely qualified to asses the latest science advances.

The author gives a brief and interesting history to each subject area, to help the reader understand where today's knowledge comes from, before providing a more detailed discussion of our current questions and challenges. A particularly detailed introduction was given to rapamycin, understandable given its current dominance as a gerotherapeutic, though the indepth review of the biological effects of radiation made me wonder if it was his specialist subject rather than all entirely relevant.

Ramakrishnan appears to take a very open mind to the prospect of treatments that could slow, or even reverse, ageing. Though he rarely mentioned progress made with anti-ageing treatments. Towards the end of the book he outs himself as a deathist, agreeing with the oft-philosophised (but rarely, in my opinion, considered by the general public) idea that death gives life meaning. This did make me wonder whether not highlighting all of the longevity therapies being developed (though, to be fair, he does mention a number of biotechs) was due to reasonable scepticism or an underlying disapproval of the idea. Either way, that only underscores the rational approach taken by him to appraise the progress made so far in our understanding of ageing.


Here are 101 key points from Why We Die:

  • The knowledge of death is so terrifying that we live most of our lives in denial of it.
  • Much of aging has to do with how our body regulates the production and destruction of proteins.
  • The simplest way to think of aging is that it is the accumulation of chemical damage to our molecules and cells over time.
  • In each generation, our bodies, or our soma, are simply vessels to facilitate the propagation of our genes.
  • Menopause may have arisen to protect women from the increased risk of childbirth in later age, keeping them alive longer to take care of the children they had already.
  • It may be a very long time before any findings gleaned from hydra or jellyfish are useful to us.
  • Small mammals have more surface area for their size and so lose heat more easily... so burn more calories than larger animals.
  • Mammals typically have roughly the same number of heartbeats over their lifetime: about 1.5 billion.
  • Humans have an LQ of about 5, meaning that we live 5 times as long as would be expected for our body size.
  • Negligible senescence means that mortality, or the likelihood of dying, does not increase with age.
  • Even in the nineteenth century, when life expectancy was forty years, a person who reached adulthood had a good chance of living to be sixty or more.
  • Jay Olshansky argued that for life expectancy to increase dramatically, we would need to reduce mortality rates from all causes by 55 percent and even more at older ages.
  • Jan Vijg calculates that the probability of anyone exceeding 125 in any given year is less than 1 in 10,000.
  • About half of centenarians celebrated turning one hundred without heart disease, stroke, or non– skin cancer.
  • Centenarians survive for so long by staying healthy longer than most people, rather than going through a prolonged period of living with diseases of old age.
  • Not only do proteins give the body form and strength, but they also carry out most of the chemical reactions that are essential for life.
  • Non-coding sequences of DNA signal when to make the protein, when to stop, and even whether to make it quickly or slowly.
  • About a hundred thousand changes are inflicted on the DNA in each of our cells every single day.
  • Generally, the more effectively our bodies can repair our DNA, the more we can resist aging.
  • At the heart of the DNA damage response is a protein called p53... often called the Guardian of the Genome.
  • The number of times a particular kind of cell can divide is now called the Hayflick limit.
  • Cells stop dividing even before all of the telomeric region is lost.
  • When we are stressed, our body produces much more cortisol— referred to as the stress hormone— which reduces telomerase activity.
  • People with short telomeres are prone to degenerative diseases, whereas those with long telomeres face increased risks of cancer.
  • Mutations in individual genes have been associated with many diseases; examples include cystic fibrosis, breast cancer, Tay-Sachs disease, and sickle-cell anaemia.
  • Identical twins raised in the same environment can sometimes be very different.
  • By experimenting with transcription factors in various combinations, Shinya Yamanaka found that just four were enough to convert an adult fibroblast cell into a pluripotent cell.
  • As cells develop, they will methylate their DNA in the region of genes they want to shut down.
  • The exact pattern of methylation can be passed on to the daughter cell when a cell divides.
  • Our cells don’t just acquire mutations in the DNA affecting the underlying code itself. They also acquire epigenetic marks.
  • Naked mole rats' methylation pattern shows that it does age, just more slowly than other rodents.
  • A woman produces all the eggs she will ever have while she is still a foetus.
  • If we can overcome the technical problems of reprogramming cells then perhaps we could introduce new pancreatic cells that produce insulin in patients with diabetes, replace damaged heart muscles after a heart attack, or even regrow neurons in people who have suffered a stroke or a neurodegenerative disease like Alzheimer’s.
  • In England and Wales, dementia recently overtook heart disease as the leading cause of death.
  • The cell has evolved ways to detect and then destroy proteins that are defective to begin with or when they become aberrant later.
  • Even after a protein has already folded into the right shape, you can make it unfold.
  • The atoms in a protein jiggle around all the time, and the proteins themselves breathe and oscillate around their average shapes.
  • Proteasome activity declines with age, and we have reason to believe it is a cause of aging.
  • De Duve coined the term autophagy, from the Greek for “self-eating,” because the cell was digesting away parts of itself.
  • If you stress or starve the cell, autophagy goes up.
  • The tangles we see in diseased brains actually have very well-defined structures, each of which is a hallmark of a particular disease.
  • In prion diseases, the prion form assumes a different shape from the normal form, and spreads because it switches the normal version into the prion form when it comes into contact with it.
  • Today we face a widespread epidemic of obesity, which is linked not only to cardiovascular disease and type 2 diabetes but also to Certain cancers and even Alzheimer’s disease.
  • Sleep deprivation increases the risk of many diseases of aging, including cardiovascular disease, obesity, cancer, and Alzheimer’s disease.
  • When scientists look outside typical lab conditions to animals in the wild, the link between eating less and living longer becomes much more tenuous.
  • Most scientists working on aging agree that dietary restriction can extend both healthy life and overall life span in mice and also leads to reductions in cancer, diabetes, and overall mortality in humans.
  • Caloric restriction can slow down wound healing, make you more prone to infection, and cause you to lose muscle mass.
  • Fungi are more similar to us than bacteria are.
  • In the presence of rapamycin cells would appear starved and stop growing even when plenty of nutrients were available.
  • Tor is part of two larger complexes called TORC1 and TORC2.
  • Administering rapamycin in mice rejuvenates aging hematopoietic stem cells, the precursors of the cells of the immune system.
  • A study of 2,700 Danish twins suggested that the heritability of human longevity was only about 25 percent.
  • These genetic factors were thought to be due to the sum of small effects from a large number of genes.
  • Within species, smaller breeds generally live longer than larger ones which may have to do partly with how much growth hormone they make.
  • After a meal, the level of insulin surges by between ten-and fifty-fold, promoting the uptake of glucose into muscle cells.
  • The evidence for metformin concerning longevity is not at all clear.
  • It would take about a thousand bottles of wine to produce the amount of resveratrol used as a dose in those studies.
  • The results of taking either NR or NMN in humans are not yet definitive.
  • Mitochondria take less versatile forms of energy— for example, the carbohydrates that we consume— and convert them into the universal energy currency of the cell, ATP.
  • The efficient production of ATP allowed cells to become ever more complex and specialized.
  • More than 99 percent of the mitochondria’s components are made by translating genes that now reside on the chromosomes in our nucleus.
  • Mutations in the mitochondrial DNA can give rise to diseases, including diabetes, and heart and liver failure, as well as conditions such as deafness.
  • As we age, our mitochondria still work, but they have accumulated defects.
  • Reactive species can affect future generations of mitochondria by damaging our mitochondrial DNA.
  • An analysis of sixty-eight randomized clinical trials of antioxidant supplements, encompassing a total of 230,000 participants, suggested that not only did they not reduce mortality, but some of them— beta-carotene, vitamin A, vitamin E— actually increased it.
  • The naked mole rat lives many times longer than other animals of the same size, yet it has higher levels of reactive oxygen species.
  • One characteristic of aging is a chronic low level of inflammation, cleverly dubbed “inflammaging.”
  • Physical activity turns on some of the same pathways that stimulate mitochondrial production.
  • Senescent cells are often produced in response to injury or other damage, and the same secretions that set off inflammation also promote wound healing and tissue regeneration.
  • When researchers used an oral cocktail that selectively killed senescent cells, it alleviated the symptoms of both the young and old mice and reduced their mortality significantly.
  • Our tissues don’t all regenerate at the same rate.
  • Scientists have shown that some brain cells are renewed, albeit very slowly, at a rate of about 1.75 percent annually.
  • Stem cells themselves eventually suffer from DNA damage and telomere loss, and accumulate metabolic defects.
  • In theory, you could have factors in young blood that stimulate growth and improve function; by the same token, old blood might contain factors that made things worse.
  • GDF11 in mice reversed age-related deterioration of muscle tissue by reviving stem cells in old muscles and making them stronger.
  • Bryan Johnson stopped the transfusions from his son after seeing no benefits himself.
  • cryopreservation studies how to freeze samples so that they are still viable when thawed later.
  • Enter cryonics, in which entire people are frozen immediately after death with the idea of defrosting them later.
  • Not one of these cryonics companies has produced any evidence that its procedures preserve the human brain in a way that would allow future scientists to obtain a complete map of its neuronal connections.
  • I would worry about the longevity of these [cryonics] facilities, and even the societies and countries in which they exist.
  • Aubrey de Grey asserts that the first humans who will live to be 1,000 years old have already been born.
  • David Sinclair is known for excessive self-promotion and highly enthusiastic claims.
  • Telomere shortening may play a role in limiting cellular life span, but long-lived species often have shorter telomeres than do short-lived ones.
  • Today there are more than 700 biotech companies focused on aging and longevity.
  • Gerontology has gone from being a somewhat disrespectable soft science scorned by mainstream biologists to becoming a major research priority.
  • The mechanism of action of the antidiabetic drug metformin is still not well understood.
  • A variety of markers may enable scientists to measure if their treatments are having any effect on aging without having to wait an interminably— or terminably— long time.
  • In the scientific community, debate rages over whether aging is simply a normal progression of life or a disease.
  • Classifying aging itself as a disease could lead to inadequate care from physicians: rather than pinpoint the cause of a condition, they would simply dismiss it as an unavoidable consequence of old age.
  • Most people say they do not fear death so much as the prolonged debilitation that precedes it.
  • Data from the Office of National Statistics in the UK suggest that rather than compressing morbidity, advances in treatment of age-related diseases have done the opposite.
  • Although the number of centenarians has grown in recent decades, the numbers of semisupercentenarians and supercentenarians have not.
  • Virtually every part of the world is experiencing a growth in the size and proportion of the population over the age of sixty-five.
  • The poor not only live shorter lives but also spend more of it in poor health.
  • Large percentages of people dislike their jobs and look forward to retirement.
  • All the evidence suggests that in general, we are no longer as creative and bold as when we were younger.
  • As we grow older, one of the first mental abilities to decline is our short-term memory.
  • In both Britain and American, households where the head is over seventy have about fifteen to twenty times the median wealth of those under thirty-five.
  • We must not use chronological age as a proxy for ability.
  • There is a lot of evidence that having a purpose in life reduces mortality from all causes.
  • If someone were to offer a pill that would add ten years of healthy life, hardly anyone would decline it.

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See also: Academic Venki Ramakrishnan - British-American structural biologist, Nobel prize winner and author

Details last updated 23-Jun-2024

Topics mentioned on this page:
Ageing Research, How To Live Forever