I bought The Longevity Seekers in 2016, at the same time I bought a large number of other aging books. So it wound up on a shelf and by the time I left for a cruise around the world 3 years later I still hadn’t read it. So I brought it with me.
I started reading it on June 1st (2019) and finished reading it on June 6. It turned out it was a really good book, well written and entertaining, as well as having a lot of information about the pace at which aging science exploded between 2002 and 2013 when the book was published. Now I wish I had read it long before…
These are my notes on the book, listed here partly for my own use but also so my readers can have an idea of the book and perhaps encourage them to buy it.
These are my notes from reading the book:
Pg 4: Some of the theories of aging.
Pg 4: Hayflick limit (this is the number of times a cell will replicate).
Pg 5: Clive McCay in 1934 published “Prolonging the Lifespan” in which he observed calorie restriction extended the lifespan of rats and mice by 40%.
Pg 5: Walford’s book “Maximum Lifespan” published in 1983 which is what drew me firmly into the scientific field of aging. Before this book I had been keen on the subject, but this was the first hint that lifespan was flexible.
Pg 6: Disposable soma theory of aging. [$*$*link]
Pg 8: Some cells are programmed to die.
Pg 8: Just a few similar genes determine development (body plan) in many different species.
Pg 9: Paramecium rejuvenate after sex and grow old if they don’t reproduce sexually.
Pg 11: “Aging was an intractable scientific problem.”
Pg 14-22: A chapter about Cynthia Kenyon, one of the great aging scientists.
Pg 18: Stanley Prusiner discovered prions and Elizabeth Blackburn discovered telomeres.
Pg 18: The HOX genes.
Pg 20: daf-2 mutant genes doubles lifespan in C. elegans (a tiny worm).
Pg 21: daf-16 is needed for lifespan extension with daf-2.
Pg 24: Michael Rose tricked flies into extending lifespan by only allowing late breeding.
Pg 25: “Ageless Quest” book (autobiography) by Leonard Guarente.
Pg 27: Yeast UTH gene extended lifespan in yeast but also caused infertility.
Pg 30: NAD is made from Vitamin B3 (niacin).
Pg 32: Early aging gene discoveries stimulated many new researchers.
Pg 36-7: The worm daf-2 is insulin (basically).
Pg 40: Pope Innocent VII tried to revive himself with a blood transfusion from a young man (1942).
Pg 47: Ames Dwarf mice have a mutation in PROP-1 (pituitary factor-1) and live 50% longer because of it.
Pg 48: Long life linked to smaller size, but to a lesser extent in humans.
Pg 45: SAGE KE = Science of Aging Knowledge Environment (from internet: Active from October 2001 to June 2006)
Pg 49: Adrzej Bartke made a flowchart of aging theories
Pg 67: Worms modified to live 6 times longer, and 2 of them lived 10 times longer (same as a person living to 780 years old!!)
Pg 69: Metformin increased mouse longevity by 38%
Pg 69: AMPK = cell fuel gage
Pg 71: Book: The Structure of Scientific Revolutions by Thomas Kuhn
Pg 73: Molecular biology of aging made many theories of aging merge toward antagonistic pleiotropy
Pg 74: Adrzej Bartke showed that the insulin pathway worked separately from calorie restriction and when both were applied it doubled mouse lifespan.
Pg 74: Computational biology of aging is a new field in (2005?)
Pg 75: Calorie restriction started in middle life increased lifespan by increasing APM-kinase which increased FOXO.
Pg 75: Brunet lab has public and foundation funding.
Pg 76: Gene chips showed only a few genes change their transcription rate in aging.
Pg 77: Can measure aging by measuring lipofuscin levels
Pg 77: “Aging is not programmed” says Steve Austad
Pg 79: Easter Island statues “look out to sea” <–wrong
Pg 80: 20 month old mice given rapamycin lived 20% longer. This is like a 60 year old human getting 20 years of healthy life instead of 10.
Pg 81: Valter inhibited mTOR and extended yeast lifespan by 10 times!
Pg 81: Rapamycin cost (2005?) $1,000 a week.
Pg 81: The Biology of Aging, a book by R. Arking (Observations and Principals)
Pg 82: Cells treated with resveratrol increased in number and health of mitochondria.
Pg 83: Resveratrol decreases the impact of a high fat diet and increases health of mitochondria.
Pg 87: Sequoia live to 1,000 years old.
Pg 88: Bowhead whales live to 200 years old.
Pg 91: Effect of an individual’s genes shaped by diet, environment experience and chance.
Pg 91: Grandmother theory (last paragraph).
Pg 91: Kinship dynamics is a new field about grandmother effect.
Pg 92: Seabirds maintain telomere length their whole life.
Pg 93: Naked mole rat has stress-protected version of Nrf2, “which preserves to power of proteins to fold properly”.
Pg 93: Many late-life illnesses are disease of protein folding.
Pg 93: Chaperone proteins unfold and refold bad proteins.
Pg 94: Dutch in WWII famine (pg 95) led to epigenetic changes if first 3 months of gestation were in starvation.
Pg 95: FOXOa gene found in Ashkenazi Jews and others.
Pg 97: GlaxoSmithKline restructured to be units no bigger than 100 people.
Pg 98-9: Aging is a network.
Pg 103: Rando says “[aging]…decline in structure and function. The cause is a network of influences and effects with…nonlinearity and feedback.”
Pg 105: Brunet studied overlapping networks of FOXO3/calorie restriction/AMP-kinase.
Pg 105: Rapamycin extends lifespan in older mice by 30%.
Pg 106: FOXO gene triggered in worm body sets it’s embryo clock to 0.
Pg 106: Genes influence health aging by slowing it, molding it, etc.
Pg 106-7: Four molecular pathways make overlapping networks modulate longevity.
Pg 109: Derek Lowe runs a blog.
Pg 107-110: Resveratrol does not appear to affect lifespan.
Pg 111: Evolutionary distance between (human:fly) is less than (fly:work)!
Pg 115: “Proper protein shape is a key to late-life health.”
Pg 115: Misfolded proteins clump and clog signaling pathways and play a roll in aging diseases from cancer to Alzheimers and most significantly heart disease.
Pg 117: “Aging is a network of feedback loops in humans.” says Erik Kapernick.
Pg 117: 247 known or suspected longevity genes.
Pg 119: Metformin tested in 1,100 clinical trials!
Pg 122: Cancer is rare in young people because they use same cytokines as those used by the naked mole rat to attack damaged cells.
Pg 125: Epigenetics causes “gene scars” in aging lab animals.
Pg 125: Stem cells of cancer patients age faster than normal.
Pg 125: Epigenetics ==> “cell response to DNA damage is probably more important to aging than the damage” says David Sinclair.
Pg 131: FOXO gene extends lifespan when activated and can be activated by diet.
Pg 132: FOXO3a prevents bone loss.
Pg 132: Centenarians have more and larger HDL, controlled by the CETP gene.
Pg 132: Mitochondria secrete peptides that decrease with age that have anti-diabetic, anti-Alzheimers and anti-atherosclerotic properties.
Pg 133: A single gene does not create a single protein, but many.
Pg 133: Book: “Genes and What to Make of Them” by Barnes & Dupre.
Pg 134: Encyclopedia of DNA elements (ENCODE) suggested most DNA diseases are caused by switching errors.
Pg 137: “Aging programmed…proteins fall apart…[stop] reproduction.”
Pg 137: To live longer need to hit 2+ longevity programs.
Pg 142: List of non-profits about aging or that serve old people.
Pg 142: From 1990 to 2008 lifespan decrease about 3 years for males and 5 years for females.
Pg 144: By 2050 human lifespan will increase as much as 30 years.
Pg 148: Olshansky’s PhD thesis = new ways to calculate life expectancy that is still in use by some insurance companies.
Pg 149: Olshansky book: “The Quest for Immortality”.
Pg 150: UK fertility rate fell from 5 per woman to 2 took 150 years; South Korea it took 20 years (1965 to 1985).
Pg 151: Vitamin D in milk.
Pg 152: Memory is improved by motivation to improve.
Pg 154: Volunteerism is worth $272 billion in the US.
Pg 155: Fasting during chemotherapy increases resistance to radiation.
Pg 155: Mitochondria mutate as we age.
Pg 156: Science is never perfect.
Pg 158: 4 major signaling pathways control aging rate.
Pg 159: Epigenetics can be inherited through 4 generations.
Pg 164: By 2014 there were 1,400 clinical trials for rapamycin, 1,100 for metformin, 58 for resveratrol, 11 for mitiglinide, a blood-glucose lowering drug.
Pg 164: Sirolimus is the drug name for rapamycin.
Pg 165: Private money poured into aging research.
Pg 166: 1.5-2 billion invested in aging in “the last decade” (2002-2012?)
Pg 167: Aging is still an immature sciences, in the adolescent phase of rapid growth.
Pg 171-5: Where people mentioned in the book currently are (as of publishing in 2013).
Pg 179-80: Longevity gene timeline.
Pg 183: McCay’s reference (1934).
Pg 187: Reference to “A cause of Yeast Aging” in Cell 1997.
Pg 211: Reference to clinicaltrials.gov (resveratrol)