Exceptional longevity: why some people live to be more than 100-year old

Interventions that promote longevity, remembered by mnemonic: DEEP purple - “eat colorful plant foods: Dietary modification, Exercise, active Engagement, Purposeful living (click here to enlarge the image).

Based on a Mayo Clinic Proceedings article (https://www.mayoclinicproceedings.org/article/S0025-6196(18)30792-4/):

Exceptional Human Longevity: the oldest old have an extreme phenotype of delayed onset of age-related diseases and/or resistance to lethal illnesses occurring earlier in life.

Centenarians have delayed onset of chronic diseases

During the span of human history the likelihood of living from birth to age 100 rose from 1 in 20 million to 1 in 50 as of year 1995 (for females in low-mortality nations such as Japan and Sweden). By 2009, this probability increased to 1 in 2. About 1 in 5,000 persons in the United States is a centenarian or older. Human longevity now exceeds 115 years. However, maximum life span has remained largely unchanged. There is a limit to human longevity, and it may be around 120 years.

In centenarians, the age at onset of common age-associated diseases is delayed: 43% of both male and female centenarians reach the age of 80 years before experiencing age-associated illness.

There is an absence of any disease diagnosis in some 15% and 30% of female and male centenarians, respectively, at the age of 100 years!

As many as 25% of centenarians are cognitively intact.

Geographic Clusters

Geographic Clustering of Exceptionally Long-Lived Individuals: Countries with the world's oldest populations in 2015: Japan, followed by Germany, Italy, Greece, Finland, and Sweden.

Long-lived Okinawans subscribe to the nutritional behavior of “hara haci bu” or “eat until you are only 80% full.” Their “rainbow diet” is based on diverse fruits and vegetables, with soy providing the bulk of protein intake. Their daily caloric intake is reduced, accounting for their low BMI of 20.

Life span is increased in regular churchgoers, whatever their faith. Seventh Day Adventists exhibit significantly lower levels of measured stress hormones.

Behavioral and environmental influences that may contribute to longevity in the so called “blue zones”:

- Eating in moderation, mostly plant-based diet. Small-portioned “regular” meals. Lighter meals at the end of the day.
- Purposeful living: life philosophy, volunteerism, “hard work” or “work ethic”
- Social support systems: interactions with family/friends, laughter/humor
- Exercise, especially walking, gardening
- Other nutritional factors: goat's milk, red wine, herbal teas
- Spirituality
- Maintenance of a healthy body mass index (BMI)
- Other possible factors: sunshine, adequate hydration, naps

Compression of Morbidity: diseases occur later in life. Fries' “compression of morbidity” hypothesis: chronic morbidity begins at a later age.

Why Are Some People Long-Lived?

Genes: Centenarians' offspring have an increased likelihood of surviving to 100 years and exhibit a diminished prevalence of age-associated diseases.

Environmental factors exert even greater effect than genes.

Sex Differences: Universally, women live longer than men. Despite the greater longevity of women, functional status is better in older men compared with older women.

Resiliency is the capacity to adequately respond to stressors. It helps resist age-related physiologic changes. Resiliency protects against insults that shorten life and health span. Resiliency can explain why some centenarians, despite onset of chronic disease before the age of 80 years, live exceptionally long.

How Is Exceptional Longevity Achieved?

Caloric restriction delays the aging phenotype in mammals. This is shown by abundant studies. Caloric restriction delayed the onset of diabetes, cancer, cardiovascular disease, and brain atrophy.

Reduced calorie intake by 20% to 60% retards aging. It only works if such reduction is quite substantial.

What about exercise? Regular physical activity promotes healthy human life span. However, it is unclear if exercise increases maximum longevity.

Normal body weight confers the most protection from mortality.

Active engagement and development of social networks and support systems confer longevity benefits. Lack of strong social relations is associated with a mortality risk roughly equivalent to smoking.

Interventions that promote longevity can be remembered by the mnemonic: DEEP purple - “eat colorful plant foods”:

- Dietary modification
- Exercise
- active Engagement
- Purposeful living

How to Measure Successful Aging?

Several algorithms have been proposed to estimate biological age. They are based on functional as well as biochemical measurements.

Biomarkers of Aging Processes and Longevity:

Disease-free survival or disability-free survival at 6-month intervals
Time to impairment in the next activity of daily living
Length of stay after hospitalization
Height, especially in men
Facial features
Gait speed, grip strength, muscle mass, mobility stress test
Daily and instrumental activities of daily living
Cognitive tests such as the Digit Symbol Substitution Test or Montreal Cognitive Test
Blood glucose or hemoglobin A1c, hypertension and elevated lipids, interleukin 6, insulin-like growth factor 1, and insulin-like growth factor binding proteins
CD4+, CD28− and CD8+, CD28− T cells; percentage of T cells that are naive vs memory (CD4 cells, CD8 cells)
Antibody response to annual influenza vaccination; delayed hypersensitivity skin test
Threshold for hearing high-pitched tones; tests of taste and smell
Tests of proprioception and balance
Forced expiratory volume in 1 second
Number of remaining teeth
One or two parents reaching 90 years of age
Educational attainment
More speculative: DNA methylation indices; senescent cell burden



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