B I O LO GY
Reversal of Aging in Mice
Image courtesy of Wikimedia Commons. Available at http://upload.wikimedia.org/wikipedia/commons/8/8d/Botulinum_toxin_3BTA.png
BY HEERUK BHATT ’18 Figure 1: Botulinum toxin is a neurotoxic protein marketed under the name Botox for cosmetic use in preventing wrinkle development.
Aging is often associated with a general decline in the functions of the body. As individuals age, their muscles reduce in size, their bones become more fragile, and their heart pumps blood at a slower rate (1). Although all organisms must grow old, mankind seems to have an obsession with reversing the aging process. From a global perspective, the value of the anti-aging market has increased by nearly $100 billion in the past five years. Plastic surgeries involving botulinum toxin, commonly referred to as Botox, that can remove facial wrinkles and restore a youthful look increased by 680 percent from 2000 to 2012 and continue to gain media attention (2). In the past two years, several scientific breakthroughs have emerged in anti-aging. In December 2013, Dr. David Sinclair of Harvard Medical School published a study in which he established a functional link between aging and the loss of a coenzyme in the bodies of mice as they age (3). Complementing this study, in May 2014, research from the Harvard Stem Cell Institute showed that injection of a certain protein in aging mice could strengthen their hearts, muscles, and brains so that they more closely resembled those of younger mice (4). And, very recently, on March 9th, 2015, scientists from the Scripps Research Institute found that an anti-cancer drug and an antihistamine may be the key in reversing the aging process (5). Although significant, none of these studies have garnered much attention from the media.
The Biology of Aging Several explanations exist for the cause of aging, although a single reason has not yet been clearly identified. When the major molecules in cells, such as DNA and proteins, become damaged, 16
cells lose their ability to divide and subsequently undergo apoptosis, or programmed cell death. Apoptosis often leads to the destruction of surrounding stem cells, resulting in inhibition of regeneration (6). This “damage” theory also seems to account for increased susceptibility to cancer (7). The shortening of telomeres is also often associated with aging. These repetitive DNA sequences are found at the ends of sister chromatids that make up chromosomes in human cells. Every time a cell divides, its telomeres shorten. When these telomeres reach a certain minimum size after around fifty rounds of division, known as the Hayflick limit, the cell loses its capacity to divide and becomes a senescent cell (6). Senescent cells are unique in that apoptosis cannot target them. When too many senescent cells accumulate in the body, they secrete harmful substances that can affect other, “healthier” cells that have not reached their division limit, accelerating the aging process (5). Other processes in the cell contribute to aging. Normally, when oxygen enters the body, it aids in the process of cellular respiration in the mitochondria by acting as the final electron receptor in the electron transport chain. Under ideal conditions, molecular oxygen accepts four electrons and is converted to water. Oxygen may accept fewer electrons, however, and, when this occurs, the molecule becomes a highly unstable and reactive species that can exit the mitochondria and damage other parts of the cell. This “oxidative stress” can damage multiple components of the cell, including proteins and the cell membrane, and can lead to widespread apoptosis, triggering the aging process. Some scientists believe that aging coincides with a reduction in sex hormones in the body, DARTMOUTH UNDERGRADUATE JOURNAL OF SCIENCE