Centenarian Biology: What People Who Live to 100 Actually Have in Common
Centenarian research — the systematic study of people who live to age 100 or beyond in good health — offers a different and complementary perspective on longevity compared to epidemiological risk factor studies. Rather than identifying what kills people earlier, centenarian studies ask what protects people against the diseases of aging for an extraordinarily long time. The findings are both predictable and surprising.
- Exceptional longevity runs in families: siblings of centenarians had lower death rates throughout life, and sisters died at about half the national rate at every age.1
- In Ashkenazi Jewish centenarians, mutations that reduce IGF-1 receptor activity were overrepresented, together with higher blood IGF-1 levels, pointing to reduced IGF signaling rather than low IGF-1.3
- Centenarians and their children had larger HDL and LDL cholesterol particles, a pattern linked to less hypertension, heart disease and metabolic syndrome and to a variant in the CETP gene.4
- Centenarians' children avoid or delay cardiovascular disease and its risk factors compared with people of the same age.2
- In a study that followed men from early adulthood, factors measured before age 50, several of them within personal control, predicted healthy or unhealthy aging at 70 to 80.5
Centenarian research studies the small fraction of people who reach 100. Because families share genes and environments, family studies are a natural starting point: they show where the advantage lies, though not always why.
Longevity in Families
In a study of 2,092 siblings of centenarians, compared with people born around 1900, brothers were at least 17 times and sisters at least 8 times as likely to reach 100 themselves.1 The sisters had death rates about half the national level at all ages, and the brothers had a similar advantage at most ages.1
The advantage extends to the next generation: centenarians' children avoid or delay cardiovascular disease and cardiovascular risk factors compared with age-matched controls.2 Because siblings and children share both genes and upbringing, these studies cannot separate the two.
IGF-1 and the Growth Hormone Axis
Loss-of-function mutations in the insulin/IGF-1 pathway extend lifespan in yeast, worms, flies and mice. In Ashkenazi Jewish centenarians, heterozygous mutations in the IGF-1 receptor gene were overrepresented and went with high serum IGF-1, suggesting that reduced signaling through the receptor plays a role in human lifespan.3
The CETP Finding and Lipoprotein Quality
In a study of 213 Ashkenazi Jewish people with exceptional longevity (mean age 98.2) and their offspring, both groups had significantly larger HDL and LDL particles than controls. This pattern went with a lower prevalence of hypertension, cardiovascular disease and the metabolic syndrome, and with more frequent homozygosity for a variant (I405V) in the CETP gene, which regulates lipoprotein particle size.4
Do Centenarians Stay Healthy Longer?
Often, but not always. A study of 424 centenarians aged 97 to 119 looked at when ten common age-related diseases, including hypertension, heart disease, diabetes, stroke and cancer, first appeared, using health-history questionnaires completed by the centenarians or their proxies.6 "Survivors" had been diagnosed before age 80 (24% of men and 43% of women); "delayers" reached 80 before their first diagnosis (44% of men and 42% of women); and "escapers" reached 100 without any of these diagnoses (32% of men and 15% of women).6
The very oldest show the pattern most clearly. A study that followed 104 supercentenarians (aged 110 to 119), 430 people aged 105 to 109 and 884 centenarians, along with 343 people in their nineties and 436 younger controls, for an average of 3 years, found that the older the group, the later cancer, cardiovascular disease, dementia and stroke tended to begin, and the smaller the share of life spent with disease; the relative risk of each disease also became progressively smaller with each older age group.7 Near the limit of human lifespan, the researchers generally observed a compression of morbidity: illness squeezed into a short period at the end of life.7
How Much of Longevity Is Genetic?
Less than family resemblance suggests. Using public Ancestry family trees covering hundreds of millions of historical people, researchers found that lifespan correlations between relatives matched earlier heritability estimates of about 15% to 30%, but most of that correlation also appeared between in-laws, who share no genes.8 After accounting for people's tendency to choose partners with similar lifespans, they estimated the true heritability of longevity for people born in the 1800s and early 1900s at well below 10%.8
That fits the family studies above, since relatives share homes, habits and circumstances as well as genes. Family clustering is most striking at the extreme: brothers of centenarians were at least 17 times as likely to reach 100 themselves.1
Psychology and Lifestyle
A study that followed men from early adulthood found that healthy or unhealthy aging at 70 to 80 could be predicted by factors measured before 50. Once the factors within personal control were accounted for, depression was the only factor outside personal control that still affected how well they aged.5
Studies like these show associations. They cannot show that a trait or habit causes exceptional longevity, because people who live to 100 may differ in many ways at once.
Put this research into practice: Gene Variant Lookup
References
- 1Perls TT, et al. "Life-long sustained mortality advantage of siblings of centenarians." Proc Natl Acad Sci U S A. 2002;99(12):8442-7. PubMed · DOI
- 2Terry DF, et al. "Cardiovascular disease delay in centenarian offspring: role of heat shock proteins." Ann N Y Acad Sci. 2004;1019:502-5. PubMed · DOI
- 3Suh Y, et al. "Functionally significant insulin-like growth factor I receptor mutations in centenarians." Proc Natl Acad Sci U S A. 2008;105(9):3438-42. PubMed · DOI
- 4Barzilai N, et al. "Unique lipoprotein phenotype and genotype associated with exceptional longevity." JAMA. 2003;290(15):2030-40. PubMed · DOI
- 5Vaillant GE, Mukamal K. "Successful aging." Am J Psychiatry. 2001;158(6):839-47. PubMed · DOI
- 6Evert J, et al. "Morbidity profiles of centenarians: survivors, delayers, and escapers." J Gerontol A Biol Sci Med Sci. 2003;58(3):232-7. PubMed · DOI
- 7Andersen SL, et al. "Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span." J Gerontol A Biol Sci Med Sci. 2012;67(4):395-405. PubMed · DOI
- 8Ruby JG, et al. "Estimates of the Heritability of Human Longevity Are Substantially Inflated due to Assortative Mating." Genetics. 2018;210(3):1109-1124. PubMed · DOI
