In 2010, individuals aged 65 years and older constituted approximately 12.9% and 8% of the population in the United States and worldwide, respectively [1
]. This number is expected to increase dramatically as millions of individuals from the baby boom generation born between 1945 and 1964, continue to reach this age. Thus, the ability to prevent and treat aging-associated diseases is rapidly becoming a primary focus in various sectors of the biomedical field.
Aging-associated diseases include degenerative conditions affecting tissue and organ function. For example, neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS) are conditions marked by the progressive deterioration of structure and function leading to neuronal death. A retinal disorder, age-related macular degeneration, is caused by the gradual degeneration of cells in the macula of the retina and is the leading cause of vision loss in adults over age 55. Conditions such as osteoarthritis and osteoporosis, which are marked by the degeneration of cartilage and bone, respectively, cause the majority of knee, joint, hip, and spine injuries in older individuals.
Aging-associated diseases may also arise from cell dysfunction. Such conditions may include cancer, heart disease, chronic obstructive pulmonary disease (COPD), and diabetes. Cancer is caused by metabolic changes in cells that lead to DNA damage that can fuel the uncontrollable and inappropriate proliferation of cells. The risk of cancer increases significantly with age. Heart disease is typically caused by prolonged exposure of the heart to hypertension, hypercholesterolemia,diabetes, and other cardiovascular risk factors, as well as an age-dependent increase in the prevalence of left ventricular hypertrophy, diastolic dysfunction, and atrial fibrillation [2
]. COPD is a group of progressive diseases of the respiratory system that includes emphysema, characterized by the destruction of alveolar cells lining the lung epithelia, and chronic bronchitis, which is caused by abnormal mucus production along the bronchial airways [3
]. In the case of ‘adult-onset’ type 2 Diabetes, pancreatic islet β-cell function can be impaired such that insufficient insulin is produced, or cells become resistant to insulin [4
The prospect of repairing or replacing damaged, dysfunctional or missing cells with new functional cells has shifted the therapeutic paradigm toward restoring tissue function in individuals affected with aging-associated diseases. The primary candidate for the development of these therapies is stem cells, particularly human embryonic stem cells (hESC), which has the capacity to self-renew indefinitely and differentiate into all tissue-specific cell types (Figure ). In this review, we will describe the derivation, maintenance, and properties of pluripotent hESCs. We will also outline the methods used to induce the generation of specific cell types from hESCs, with primary focus on cell types that are applicable in understanding the pathology, as well as a potential source of cell-based therapies, in aging-associated diseases.
Generation of pluripotent human embryonic stem cell lines.