**2.2 Animals**

The lifespan in animals is between few hours to few hundred years. The shortest lifespan is seen with mayfly (up to 24 hours). The longest lifespan is observed with clam (more than 400 years). Ming the clam was the oldest clams ever discovered (507 years old). Ming was accidentally killed in 2006 during a fact-finding mission (**Figure 2**).

**Figure 2.** *Ming the clam lived 507 years (Picture downloaded from the internet "Google Images").*

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

#### **2.3 Humans**

The theoretical lifespan in humans is around 120 years. However, very few individuals reach this theoretical age since several events can impact longevity (e.g., diseases, suicide, accident, and war).

Human aging results from accumulation of genetic, molecular, and cellular damages. It is a multifactorial process. There are several theories explaining the aging phenomenon. The most wildly accepted theory of aging is the free radical theory [7]. According to this theory, continuous, unrepaired oxidative damage of macromolecules constitutes the molecular basis of aging.

Aging and lifespan are influenced by multiple factors including genetic, epigenetic, lifestyle, environmental, metabolic, and endocrine factors [3, 8–14, 21, 26–41].

Extending longevity while keeping health and vitality has been a dream for mankind since ancient times. The "successful aging" which is a high priority for individuals and societies, is aging without any disabilities and severe diseases [42, 43]. The fountain of youth is a mythical spring capable of restoring the youth of anyone who drinks or bathes in its water (**Figure 3**).

#### **Figure 3.**

*The fountain of youth (from Erhard Schön, 1525) is a mythical remedy to aging (Picture downloaded from the internet "Google Images").*

#### *2.3.1 Physiological changes associated with aging*

With aging, there is a gradual, time-dependent, and heterogeneous decline of physiological functions (**Figure 4**). The human body goes through multiple physiological changes including an overall decrease in the size of organs (e.g., brain shrinkage), endothelial pro-atherosclerotic changes, ovarian atrophy, osteopenia (predominantly in women), sarcopenia (mainly in the lower body), adipose tissue enlargement (mostly visceral fat), and skin atrophy (especially in women) (non-exhaustive list) [9, 10, 32, 41]. Some changes are very subtle (within normal ranges) with no or unknown clinical consequences. Lifestyle conditions (e.g., diet, exercise, and medications) and environmental factors (e.g., noise, temperature, and air quality) can delay or potentiate these changes.

Autophagy ("self-eating") is a major protein turnover pathway where cellular components are delivered into the lysosomes for degradation and recycling. It maintains cellular homeostasis under stress conditions. The autophagic activity decreases in aging individuals [21].

#### **Figure 4.**

*Aging is associated with a gradual decline of different functions and performances (Picture downloaded from the internet "Google Images").*

Mitochondria are major contributors to the maintenance of energy homeostasis. They are important sources of reactive oxygen species (ROS) generation. ROS can cause oxidation of macromolecules including DNA. Aging subjects have progressive mitochondrial decline [10, 11, 39, 44].

Aging is associated with a mild inflammatory state that is sometimes referred to as "inflammaging". This inflammatory state is characterized by increased blood levels of several adipokines (e.g., interleukin 6 and tumor necrosis factor alpha). Environmental factors can further modify the inflammatory state of aging [32].

Multiple endocrine changes occur with aging, affecting the body functions [9, 10, 12, 31, 35–37, 39–41, 45–49]. The hypothalamus, an endocrine structure located in the brain that is a master regulator of multiple hormonal secretion, plays a central role in aging. With aging, the sensitivity of the hypothalamus to different feedback signals decreases [36]. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels decline during aging [37]. According to most studies, free triiodothyronine (T3) levels decrease while reverse T3 (rT3) and thyroid-stimulating hormone (TSH) levels increase [45–47] with aging. Significant hormonal change occurs in women at menopause with important reduction in estrogen (E) levels [48]. In men, testosterone (T) levels decrease gradually with age [40]. There is an important decrease in dehydroepiandrosterone (DHEA) levels in aging individuals [49]. Adipose tissue, which is the largest endocrine gland, secretes several adipokines. With aging, there is an increase in the levels of most adipokines (e.g., leptin, resistin, interleukin 6, tumor necrosis factor alpha, and adiponectin) [41].

**Parameter Change** Mitochondrial activity Decrease (gradual) Autophagic activity Decrease (gradual) Inflammatory state Increase (gradual) GH Decrease (gradual) IGF-1 Decrease (gradual) T3 Decrease (gradual) rT3 Increase (gradual) TSH Increase (subtle, at old age) E (females) Decrease (abrupt, at menopause) T (males) Decrease (gradual) DHEA Decrease (gradual) Adipokines Increase (gradual) Insulin resistance Increase (gradual)

The relevant metabolic/hormonal changes during normal aging are reported in **Table 1**.

**Table 1.** *Relevant metabolic/hormonal changes during normal aging.* *The Centenarians: An Emerging Population DOI: http://dx.doi.org/10.5772/intechopen.96327*

### *2.3.2 Genetic and epigenetic factors affecting aging and lifespan*

Genes play an important role in the regulation of aging and lifespan [3, 8, 10, 27–29, 31, 50]. Extensive number of genes (between 300 to over 700 genes) have been listed [28, 29]. Genes include *APOE1*, *ATM*, *BCL*, *CETP*, *FOXO3A*, *HSPA*, and *TERC* (non-exhaustive list). Genetic factors that are associated with longevity are heritable [27]. Several endocrine and metabolic pathways are linked genetically with aging and contribute to different phenotypes [31]. Multiple gene mutations leading to delayed aging and increased lifespan have been discovered over the last three decades. Many of the affected genes are components of endocrine-signaling pathways (e.g., GH and IGF-1 pathways).

A dramatic example of genetic impact on aging and lifespan is observed with Hutchinson-Gilford progeria syndrome, a rare sporadic, autosomal dominant syndrome that causes premature aging. In most cases, the disorder is due to a mutation characterized by a change from glycine GGC to glycine GGT in codon 608 of exon 11 of the lamin A (*LMNA*) gene causing the production of an abnormal lamin A (progerin). Progerin accumulates in cells' nuclei and exerts multiple toxic effects [50]. The affected individuals generally die from myocardial infarction or stroke around a mean age of 15 years (**Figure 5**).

Epigenetic processes also influence aging and lifespan [8, 9, 11, 26, 30].

#### **Figure 5.**

*Subject with premature aging due to Hutchinson-Gilford progeria syndrome (Picture downloaded from the internet "Google Images").*

#### *2.3.3 Lifestyle and environmental factors affecting aging and lifespan*

Lifestyle (e.g., diet, sleep, smoking, exercise, stress, and medications) and the environment (e.g., household, social condition, noise, temperature, and air quality) play an important role in the aging process and lifespan (**Figure 6**) [8, 9, 26, 51].

Caloric restriction, physical fitness, and good air quality can delay aging and increase lifespan. Conversely, excessive food consumption, sedentary lifestyle, and air pollution will have a negative impact on aging and lifespan.

#### **Figure 6.**

*Lifestyle and environmental factors can affect aging and lifespan (Picture downloaded from the internet "Google Images").*
