*3.1.2 Prevalence by country*

Currently, USA has the highest number of centenarians, followed by Japan, China, India, and Italy. Japan and Italy have the highest proportion of centenarians to the total population. By 2050, China is expected to have the largest centenarian population, followed by Japan, USA, Italy, and India (**Table 2**).


#### **Table 2.**

*Number of centenarians worldwide and in top five countries (United Nations and national sources).*

The oldest supercentenarian with well-documented age was Jeanne Louise Calment (1875–1997) from Arles, France who lived 122 years (**Figure 11**). She married at the age of 21 years, had one pregnancy (gave birth to a girl), and never worked. With the exception of migraines and bilateral cataracts, she was quite healthy and remained mentally sharp until the end of her life. She did daily gymnastics and was socially active. She never took any medication apart from aspirin for migraines. She enjoyed chocolate, drank a small daily amount of wine, smoke a cigarette after each meal, and took a nap in the afternoon. She also had a good sense of humor. To the question "Why do you live so long?", she replied "Because God has forgotten me".

#### **Figure 11.**

*Jeanne Louise Calment from Arles, France (1875–1997), the oldest confirmed supercentenarian who lived 122 years (Picture downloaded from the internet "Google Images").*

#### **3.2 Physiological profile**

Maintenance of a proper autophagic activity may contribute to extended longevity. Healthy centenarians have autophagy augmentation as reflected by increased levels of beclin-1, a key regulator of autophagy [57].

Lower thyroid hormone levels and higher TSH levels have been reported to be associated with increased longevity [31, 39, 45–47]. Centenarians have higher TSH levels compared to controls, partly due to a genetic background [31].

Adiponectin levels are elevated in centenarians and associated with a favorable metabolic phenotype. They may contribute to extended longevity [41, 54].

Frailty plays an important role in health outcomes and mortality. A study of Chinese centenarians demonstrated that centenarians are frailer than younger elders. Management of frailty can help achieving healthy longevity [58]. A study of centenarians living in New York City (USA) showed that despite reduced levels of physical functioning and social resources, centenarians were in good mental health suggesting high resilience and ability to adapt to age-associated challenges [59].

#### **3.3 Genetic/epigenetic profile**

There is a strong genetic influence in subjects with extreme longevity (**Figure 12**) [3, 8, 10, 27, 31]. Genetic component may include several genetic modifiers each with modest effects, but as a group, they can have a strong impact [27]. Several genotypes known to influence longevity are enriched in centenarians (e.g., *CETP-VV* and *FOXO3A-T*) [10]. Homozygosity in the 405*VV* variant of *CETP* (cholesterol ester transfer protein) gene is associated with lower concentrations of CETP, higher concentrations of high-density lipoprotein (HDL) cholesterol, and larger HDL particle size, all associated with protection against ischemic heart disease and Alzheimer disease. *FOXO3A* (forkhead box O3A) gene is a member of a family of transcription factors mediating insulin action and stress resistance. Several gene mutations responsible of extended longevity are components of endocrine-signaling pathways. For example, centenarians have a variety of genetic alterations in the GH/IGF-1 pathway causing reduced function of GH/IGF-1 pathway that is associated with protection from aging.

Epigenetic processes might also play a role in extreme longevity [8, 9, 11, 26, 30].

**Figure 12.** *Several longevity genes are enriched in centenarians (Picture downloaded from the internet "Google Images").*

#### **3.4 Lifestyle and environmental characteristics**

Lifestyle is an important signature of healthy aging and extreme longevity [26]. There are significant lifestyle (e.g., diet) and cultural (e.g., social life) differences between the native of the top five countries (e.g., USA, Japan, China, India, and Italy) that have the highest numbers of centenarians. However, centenarians share

#### *The Centenarians: An Emerging Population DOI: http://dx.doi.org/10.5772/intechopen.96327*

similarities for several lifestyle characteristics (**Figure 13**). The global calorie ingestion is reduced in centenarians in comparison to younger elders. Most centenarians have a plant-based diet, rich in vegetables, fruits, and oils, and usually a restricted intake of dairy products, red meat, and poultry [60]. A study of lifestyle of centenarians living in Zhejiang Province (China) showed significantly higher consumption of fruits, coarse cereals, and pasta, and lower percentage of smoking and engagement in daily recreational activities (watching television, listening to radio) compared to noncentenarians [61].

Additional important lifestyle and environmental characteristics of centenarians are the presence of physical and mental activities (with daily objectives), psychological resilience, optimism, flexibility, and life in small towns with little pollution and significant social relationships. A study of health and functional status of Japanese centenarians suggested that maintenance of physical independence is a key factor of survival into extreme old age [62].

**Figure 13.**

*Centenarians have several common lifestyle characteristics (Picture downloaded from the internet "Google Images").*

## **3.5 Disease occurrence and mortality**

Centenarians have variable clinical conditions. Some may have multimorbidity while others have no significant diseases. However, some of the "healthy" centenarians have signs of advanced aging (e.g., visual disorder, hearing loss, and limited locomotor capacity). Centenarian men tend to have better cognitive and physical functional status than centenarian women [3].

Most centenarians have managed to avoid ("escapers"), postpone, or overcome ("survivors") the important age-related and life-threatening diseases and disabilities (e.g., ischemic heart disease, stroke, chronic obstructive pulmonary disease, cancer, respiratory infection, type 2 diabetes, osteoporosis, and dementia) [3, 5, 6]. Supercentenarians can compress morbidity and disability to the very ends of their lives.

A study assessing the place and cause of death of centenarians in England showed that centenarians more likely die of old age/frailty and respiratory infection and less likely of ischemic heart disease and cancer compared to younger elders [4]. Centenarians are relatively protected from cancers (lower incidence, lower metastatic rate, lower mortality). It has been hypothesized that the tumor suppressor gene p53 is a key element in protecting centenarians from cancers [6]. In Spanish centenarians, the likelihood of having the wild-type genotype of *GSTT1*, which is associated with lower cancer risk, was found to be higher than control, young subjects [63]. The top cancers in centenarians are breast, colorectal, prostate, and lung cancers [64].

The main causes of mortality in centenarians compared to younger elders are reported in **Table 3**.


**Table 3.**

*Main causes of mortality in centenarians compared to younger elders.*
