Path 8 - Aging and Cell Senescence

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Aging

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the accumulation of deleterious changes in a person over time. Age is measured chronologically.
Changes are progressive, unidirectional, irreversible, and result in death
- Chronological aging may also be distinguished from "social aging" (cultural age-expectations of how people should act as they grow older) and "biological aging" (an organism's physical state as it ages).

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defined by decline of physiological functions, decreased capacity to respond to stress, and exponential increase of age specific mortality rate.
- Differences are sometimes made between populations of elderly people.
- Divisions are sometimes made between the young old (65-74), the middle old (75-84) and the oldest old (85+).

Population Aging

the increase in the number and proportion of older people in society.

Aging and Disease

Aging is NOT a disease, but can make one more susceptible to disease

Life Expecancy

the expected (in the statistical sense) average number of years of life remaining at a given age.
This parameter can vary with age.
e.g. in a population with a high infant and childhood mortality the life expectancy would be low. However, the cohort that survives to early adulthood would have a significantly higher life expectancy. e.g., the best evidence indicates that life expectancy at birth in medieval Britain was 30 years; however, the cohort that survived age 21 the life expectancy increased to 43 years to a total age of 64.

Maximum Life Span (MLS)

has stronger genetic component than life expectancy and is determined by the rate of aging.
- Can be defined as the mean life span off the most long-lived 10% of a given cohort.
- Alternatively, has been defined by the age at which the oldest known member of a species or experimental group has died.
- In humans the MLS as defined by the former definition is somewhere between 100 and 110
120

Experimental Conditions that can Increase MLS

- caloric restriction
- pharmacologic or genetic activation or inactivation of metabolically critical genetic loci
- transgenic up regulation certain genes

Infant Mortality and Life Expectancy

Life expectancy is often confused with life span to the point that they are nearly synonyms; when people hear 'life expectancy was 35 years' they often interpret this as meaning that people of that time or place had short life spans. The life expectancy generally quoted is the at birth number which is an average that includes all the babies that die before their first year of life as well as people that die from disease and war. This parameter can vary with age. For example in a population with a high infant and childhood mortality the life expectancy would be low.

In this graph, infant mortality rates in 1900 are quite high; correspondingly, average life expectancy of newborns in 1900 is very low at 47.6 years. In 1992 infant mortality rate drops to < 1% and we find that life expectancy has risen by nearly 30 years compared to data from the year 1900.

Changes in Life Expectancy

Changes in Life Expectancy at specific ages decreases as the age gets closer to the MLS
- While Life Expectancy has increased in most developed countries, the Maximum Life Span has NOT changed.

Rectangularization

The change observed in the shape of survival curves, which has been termed rectangularization, shows that more and more individuals survive to very old age, and all of them die in a very narrow time window. It has been proposed that this "compression" is due the fact that, as human life approaches its absolute biologic limits, improvements in health will contribute mostly to a reduction of morbidity but very little to further increases in life expectancy.

Healthspan

the duration of good health - NOT the same as lifespan

Lifespan Increase

The issue has significant financial and therefore political implications; a one year increase in life expectancy is estimated to cost the U.S. Social Security Administration ~$50 billion.

Aging US Population

Average life span and life expectancy in the US since 1990 have grown dramatically
--> Overall increase in the proportion of older people in the society geometrical increase in survival of older ppl --> increased medical care and social needs
- This advance in age is mostly due to improvements in sanitation, the discovery of antibiotics, and medical care
- Growth of the older population mostly due to general increase in overall population size but also influenced by declines in leading causes of mortality
Overall Increased Life Expectancy due largely to decreased infant mortality and vaccines

Population Aging Worldwide

Population aging is taking place throughout the world.

Improved survival at older ages and a low birthrate have resulted in European countries having the oldest populations in the world. Italy and Germany are estimated to have the oldest populations in Europe and the second and third oldest in the world at approximately 19% each.

Diseases of Aging = (Conditions)

Conditions, not necessarily true diseases, with no associated mortality
- common ("senile", "age-related") cataract
- common "essential" hypertension
- osteoporosis
- osteoarthritis
- nodular prostate hyperplasia (men)
- wrinkled skin
- presbyopia (loss of vision)
- brain cell loss
- monoclonal gammopathy of uncertain significance (MGUS)

Path 8 - Aging and Cell Senescence

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