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Chapter 16 of the book

Aging Well

ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.3 things to start with3 popular claims graded103 works cited

How the chapter opens

When researchers came to scan their hearts, about sixteen thousand Tsimane lived along the Maniqui River, a tributary of the Amazon in lowland Bolivia. They grew rice, plantain, manioc and corn in plots cleared from the forest, and they hunted, fished and gathered. There was no clean water, no sewerage and no electricity, and at any one time more than two-thirds of adults carried intestinal worms. Their hearts showed the lowest levels of coronary artery disease ever recorded in any population (Chapter 3). At an average age of about sixty, they still walk around sixteen thousand steps a day.1

Researchers then turned to the brain. Among Tsimane aged sixty and over, about one in a hundred had dementia; among their neighbors the Moseten, fewer still. Almost every case, in both groups, was in someone eighty or older. Tsimane brains shrink with age, as brains do everywhere, but more slowly than American and European brains, in bodies whose blood carries the marks of constant infection and inflammation.2

What the chapter covers

The argument, the studies and the stories are in the book. Get the book.

  • ·What Your Body Expects
  • ·What It Gets Instead
  • ·Cancer and the Checks Worth Having
  • ·Men and Women at Midlife
  • ·Men
  • ·Women
  • ·The Rest of the Body at Fifty

Mismatch card

The system

The whole body over a lifetime: the cells that age and occasionally turn cancerous, and the organs that fail at the end.

What it expects

Daily physical work, food that comes and goes, constant company and microbes, and death arriving mostly from outside, after a modal age in the seventies.

What it gets

Low physical load, constant food, tobacco and alcohol, and medicine that postpones death from diseases whose causes remain in place.

What happens in the gap

Longer lives with a wider strip of illness at the end; in the United States, the widest gap between lifespan and healthy lifespan of 183 countries studied.

The handrail

The five things in Chapter 1, the screenings due for your age and sex, and kept strength (ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.).

Strength of evidence

ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials. Screening rests on trials and quitting smoking on large, consistent cohorts; the links between strength, lifestyle and a shorter sick spell at the end come from cohorts and population data.

What you've heard

Popular claims this chapter tests, each with the book's verdict and grade.

The protocol

Each action carries the book's evidence grade. How the grades work.

Start here

  1. Keep up the five things in Chapter 1

    StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.for not smokingthe rest are graded there

    How: don't smoke, drink little or nothing, walk toward seven or eight thousand steps a day, cut the ultra-processed share of your food, keep a regular wake time, and see your three to five people. Why: on this book's reading, they act on six of the ten leading causes of death.

  2. Get the screenings due for your age and sex

    StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.as guideline recommendationsPSA an individual choiceskin checks unproven

    How: go through the table above with your clinician once, put the due dates in a calendar, and set reminders for the repeats. Why: for most rows the Task Force judged that benefits outweigh harms for people at average risk.

  3. Keep your strength and grip

    StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.for strengthProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.for longer life

    How: twice a week, about half an hour: sit-to-stands from a dining chair (a cushion raises the seat if your knee complains), push-ups against a wall or counter, rows with a band, and a heavy shopping bag carried in each hand (Chapters 1 and 4). Once or twice a year, count how many times you can stand up from a chair in thirty seconds without using your hands, and write it down; treat a poor score as a reason to train rather than a forecast. Why: strength falls faster than muscle bulk with age, and weakness predicts disability and earlier death.

Then, pick from this menu

  • **Know the warning signs of colorectal cancer at any age (ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.).** Rectal bleeding, iron-deficiency anemia or abdominal pain that does not settle deserve a doctor's visit.

  • **Men: treat new erectile problems as a reason for a heart check (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism. for the link; the benefit of the check is untested).** Ask for blood pressure, cholesterol and blood sugar tests.

  • **Men who suspect low testosterone: fix weight first (ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.) and protect sleep (EmergingEvidence grade: Emerging. Early, small, animal-only, or actively contested.), then test properly.** If symptoms persist, ask for two early-morning fasting tests from an accredited lab; a single afternoon reading, a saliva kit or a clinic's "optimal range" will not settle it.

  • **Vaccines from fifty (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism. for the trials behind each vaccine; US schedule as of mid-2026, which may change).** Two doses of the recombinant shingles vaccine, two to six months apart; pneumococcal vaccination; flu every year; a tetanus booster every ten years; and RSV once at seventy-five, or from fifty if you are at increased risk. Chapter 6 has the details.39

  • **A hearing test if you are over fifty or struggle to follow conversation (ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials. for hearing).** In the US, hearing aids for mild to moderate loss are now sold over the counter (Chapter 10).

  • **An eye check by forty, and reading glasses when you need them (ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials. as specialist guidance).**

  • **Skip biological-age tests, NAD+ boosters and senolytic supplements (ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.).** Why: the tests are unreliable for one person, and no human trial shows the supplements slow aging. Spend the money on shoes, a band or a grip gauge.

If this is you

Men fifty-five to sixty-nine

decide about PSA with a clinician, using the per-thousand numbers above (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism. for the trial numbers; the choice is yours). If a result is raised, ask for a repeat test, then an MRI before any biopsy (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.). If a low-risk cancer is found, active surveillance is a mainstream choice (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.).

Black men, or men with a strong family history of prostate cancer or a known inherited mutation such as BRCA

the urologists' guideline advises starting the PSA conversation at forty to forty-five (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism. as guideline advice).

Men over seventy

US guidance is not to screen routinely (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism. as guideline advice); a decision based on your health and past results is reasonable.

Men offered testosterone, by a clinic or a doctor

ask to see the two early-morning results and the symptom being treated (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.). Expect more desire, not better erections, walking, memory or bones (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.). If you might want children in the next year or two, say so before the first dose, because it switches off sperm production (StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.).

Perimenopause and after

a mammogram every two years from forty; start loading for bone now, when it thins fastest (Chapter 4); and take breast cancer risk into the hormone therapy conversation (Chapter 15).

A family history of breast or ovarian cancer

ask for a BRCA risk assessment.

You smoke now, or quit within fifteen years, and are fifty to eighty

ask whether your smoking history qualifies you for a yearly low-dose CT scan. Quitting at any age helps.

Male, in your twenties or thirties

get a usual clinician and see them, even if you feel fine (EmergingEvidence grade: Emerging. Early, small, animal-only, or actively contested. for the benefit; the gap is well measured). Young men are the least likely adults to have seen one in the past year.

Over fifty, or stiff joints

a sore knee is a reason to adjust the range and the seat height, and to keep going; Chapter 3 has knee-friendly versions.

Tight budget

the chair-stand test is free, and the tests in the table are the high-value ones; the extras sold as "full-body" scans are not in it. Ask which screening tests your plan covers, and whether a self-collected HPV swab is offered.

Short on time

one visit to set up the screening calendar does most of the work in this chapter for years.

Safety

Never start testosterone if you want children in the next year or two. Guidelines advise against starting it with prostate or breast cancer, a raised PSA not yet checked by a urologist, thickened blood, untreated severe sleep apnea, uncontrolled heart failure, a clotting disorder, or a heart attack or stroke in the past six months; on treatment, get blood counts, PSA and blood pressure checked in the first year.40 If you have heart disease, a recent injury, osteoporosis or a past fracture, start strength work under guidance. Two RSV vaccines carry an FDA warning about an increased risk of Guillain-Barre syndrome, a rare nerve disorder, in the six weeks after the shot; ask about it. Do not take senolytic drugs outside a trial. If you have thoughts of suicide, do not wait: in the US, call or text 988; elsewhere, call your local emergency number. Screening finds some cancers that would never have caused harm, so make each decision with a clinician, and never stop or skip a treatment you have been prescribed without one.

The skeptic's box

What could overturn this chapter, from the chapter itself.

The healthspan figures are modeled averages for whole countries, built on disability weights that reasonable people dispute, and part of the modern cause-of-death table is a byproduct of survival: people who no longer die at thirty of infection live long enough to develop, and be diagnosed with, cancer and dementia. Fries's compression hypothesis is still argued over. The Tsimane data are cross-sectional snapshots of a small, selected population, and one finding cuts against any tidy story: carriers of APOE4, the gene variant most linked to Alzheimer's in industrialized countries, had better-preserved thinking when their parasite load was high.41 Screening rests on randomized trials, but its benefits are counted per thousand people, and the PSA numbers could shift as MRI changes who gets biopsied. And the claim that six of ten leading causes are largely modifiable is this book's synthesis, an argument rather than a statistic.

Go deeper in the reference library

The research this chapter was built from, as longer reference entries: each with its own mismatch card, graded recommendations and the case against it.

See also in the book

Sources behind this page

  1. 1.Kaplan, H., Thompson, R.C., Trumble, B.C., Wann, L.S., et al. (2017). "Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study." The Lancet, 389(10080), 1730-1739. https://doi.org/10.1016/S0140-6736(17)30752-3; Imms, P., Chaudhari, N.N., Cummings, D., Eid Rodriguez, D., et al. (2025). "Physical activity mediates age differences in cognition among Tsimane forager-horticulturalists." Journals of Gerontology, Series A, 80(8), glaf163. https://doi.org/10.1093/gerona/glaf163 (Imms, Table 1: 570 Tsimane adults averaging about 60; 16,401 steps a day in men and 16,283 in women, by wrist-worn accelerometers worn for a mean of 4.43 days.)
  2. 2.Gatz, M., Mack, W.J., Chui, H.C., Law, E.M., et al. (2023). "Prevalence of dementia and mild cognitive impairment in indigenous Bolivian forager-horticulturalists." Alzheimer's & Dementia, 19(1), 44-55. https://doi.org/10.1002/alz.12626; Irimia, A., Chaudhari, N.N., Robles, D.J., Rostowsky, K.A., et al. (2021). "The indigenous South American Tsimane exhibit relatively modest decrease in brain volume with age despite high systemic inflammation." The Journals of Gerontology: Series A, 76(12), 2147-2155. https://doi.org/10.1093/gerona/glab138; Kaplan, H., Hooper, P.L., Gatz, M., Mack, W.J., et al. (2023). "Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations." PNAS, 120(13), e2205448120. https://doi.org/10.1073/pnas.2205448120 (Gatz: Tsimane 1.2% and Moseten 0.6% among those aged 60 and over, with essentially all cases at 80 and older.)
  3. 41.Trumble, B.C., Stieglitz, J., Blackwell, A.D., Allayee, H., et al. (2017). "Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden." The FASEB Journal, 31(4), 1508-1515. https://doi.org/10.1096/fj.201601084r (n = 372.)
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  5. 37.Horvath, S. (2013). "DNA methylation age of human tissues and cell types." Genome Biology, 14(10), R115. https://doi.org/10.1186/gb-2013-14-10-r115; Higgins-Chen, A.T., Thrush, K.L., Wang, Y., Minteer, C.J., et al. (2022). "A computational solution for bolstering reliability of epigenetic clocks: implications for clinical trials and longitudinal tracking." Nature Aging, 2(7), 644-661. https://doi.org/10.1038/s43587-022-00248-2; Waziry, R., Ryan, C.P., Corcoran, D.L., Huffman, K.M., et al. (2023). "Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial." Nature Aging, 3(3), 248-257. https://doi.org/10.1038/s43587-022-00357-y; Epel, E.S., Blackburn, E.H., Lin, J., Dhabhar, F.S., et al. (2004). "Accelerated telomere shortening in response to life stress." Proceedings of the National Academy of Sciences, 101(49), 17312-17315. https://doi.org/10.1073/pnas.0407162101 (CALERIE: DunedinPACE slowed about 2-3%, PhenoAge and GrimAge unchanged.)
  6. 38.Martens, C.R., Denman, B.A., Mazzo, M.R., Armstrong, M.L., et al. (2018). "Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults." Nature Communications, 9(1), 1286. https://doi.org/10.1038/s41467-018-03421-7; Zhang, J., Poon, E.T., and Wong, S.H. (2025). "Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials." Critical Reviews in Food Science and Nutrition, 65(22), 4382-4400. https://doi.org/10.1080/10408398.2024.2387324; Prokopidis, K., Moriarty, F., Bahat, G., McLean, J., et al. (2025). "The effect of nicotinamide mononucleotide and riboside on skeletal muscle mass and function: a systematic review and meta-analysis." Journal of Cachexia, Sarcopenia and Muscle, 16(3), e13799. https://doi.org/10.1002/jcsm.13799; Chen, F., Zhou, D., Kong, A.P., Yim, N.T., et al. (2024). "Effects of nicotinamide mononucleotide on glucose and lipid metabolism in adults: a systematic review and meta-analysis of randomised controlled trials." Current Diabetes Reports, 25(1), 4. https://doi.org/10.1007/s11892-024-01557-z; Zhang, M., Chen, Y., Jiang, N., Zeng, J., et al. (2026). "Effects of nicotinamide mononucleotide supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials." Nutrients, 18(6), 890. https://doi.org/10.3390/nu18060890; Hickson, L.J., Langhi Prata, L.G.P., Bobart, S.A., Evans, T.K., et al. (2019). "Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease." EBioMedicine, 47, 446-456. https://doi.org/10.1016/j.ebiom.2019.08.069 (Zhang 2025 pooled 12 studies and 513 people; the senolytic study treated nine people.)
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  8. 39.Centers for Disease Control and Prevention (2025). Adult Immunization Schedule Notes (page dated 2 July 2025). https://www.cdc.gov/vaccines/hcp/imz-schedules/adult-notes.html; Congressional Research Service (2026). Changes to CDC Vaccine Recommendations in 2025 and 2026 (IN12684, updated 29 July 2026). https://www.congress.gov/crs-product/IN12684; US Food and Drug Administration (2025). FDA Requires Guillain-Barre Syndrome (GBS) Warning in the Prescribing Information for RSV Vaccines Abrysvo and Arexvy. https://www.fda.gov/safety/medical-product-safety-information/fda-requires-guillain-barre-syndrome-gbs-warning-prescribing-information-rsv-vaccines-abrysvo-and (A court stay in March 2026 left the adult schedule mostly at its January 2025 version.)

Every work this chapter cites

The chapter's 41 notes cite 103 works, listed by note number. Each is also in the full source register.

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  18. 18.Bhasin, S., Brito, J.P., Cunningham, G.R., Hayes, F.J., et al (2018). Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. 10.1210/jc.2018-00229Mulhall, J.P., Trost, L.W., Brannigan, R.E., Kurtz, E.G., et al (2018). Evaluation and management of testosterone deficiency: AUA guideline. Journal of Urology. 10.1016/j.juro.2018.03.115Wu, F.C., Tajar, A., Beynon, J.M., Pye, S.R., et al (2010). Identification of late-onset hypogonadism in middle-aged and elderly men. New England Journal of Medicine. 10.1056/NEJMoa0911101Endocrine Society (2026). Statement on testosterone replacement therapy. endocrine.org
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