Behind the Brain

Aging has conventionally been viewed as both a natural and an inevitable process. However, recent developments in neuroscience and biology suggest that the pace of aging might not necessarily be the one we conventionally experience. So let’s look closely at the process of aging itself and some of the most recent research in this area.

The Neuroscience of Aging

Aging is a fundamental biological process involving the deterioration of every organ, including the brain. Aging causes cognitive decline and the loss of neural plasticity. Its causes are many and involve:

1. Cellular Senescence: The cell’s ability to proliferate and function declines with time. These senescent cells accumulate in an organ and release inflammatory signals, further contributing to the degeneration of tissues.
2. Telomere Shortening: Telomeres are the protective caps on the end of chromosomes that shorten every time a cell divides. When they become too short, the cell can no longer divide, a process that accelerates aging. This leads to either cell death (apoptosis) or senescence.
3. Oxidative Stress: Reactive molecules containing oxygen destroy cellular and nuclear structures through a gradual process that undermines cellular function. The brain has greater susceptibility to oxidative damage being a highly metabolic organ.
4. Epigenetic drift: As time passes, changes in the epigenome (chemical modifications that regulate gene expression) disrupt cellular processes, leading to aging.

Can Science Stop Aging?

While complete halting of aging is still speculation, remarkable progress has been made in understanding and delaying the aging process. Some of the promising avenues of research involve:

1. Senolytics: Senolytics represent a class of drugs that work on the selective clearing of senescent cells. With the removal of such dysfunctional cells, reduction of inflammation, and restoration of tissue function are expected. Initial studies in animals have shown improvements in healthspan by delaying the onset of age-related diseases.
2. Telomere Extension: So far, one enzyme known to extend telomeres, telomerase, has been studied as an intervention against its shortening. In animal models such as mice, activation of this enzyme resulted in the reversal of certain signs of aging without increased risk for cancer, though translation into human therapy is still difficult.
3. NAD+ Boosting: Nicotinamide adenine dinucleotide, or NAD+, is one important molecule that helps in the generation of cellular energy and in the repair of DNA. It declines with age, so supplementing its precursors has identified a new way of providing for better mitochondrial function, which may delay the aging process.
4. Gene Therapy: Gene-modifying methods, including CRISPR, are under study in attempts to alter genes associated with aging. For example, FOXO and SIRT genes associated with longevity and resistance to stress across a wide range of organisms have been targeted.
5. Neurogenesis Enhancement: Neurogenesis is the generation of new neurons, which, with increasing age, slows but still continues in discrete regions of the brain, including the hippocampus. Growth factors, exercise, and pharmacological agents are examples of methods under investigation to enhance neurogenesis.
6. Epigenetic Reprogramming: So far, one of the most encouraging ways toward cellular aging reversal in animal models has been the application of Yamanaka factors, four genes which reprogram adult cells to an induced pluripotent stem cell state. These cells then can become any type of cell, thus helping with reversing aging.

Ethical Issues

While from a purely scientific point of view, the quest for life prolongation is exciting, from a broader perspective, there is a number of ethical issues emerging. Does anti-aging therapy widen disparity across socioeconomic classes? How do global resources and social systems affect a more aged population? Perhaps, rather than reversing aging, longevity research may be more useful. Rather than focusing on reversing aging to extend lifespan, we may have to research on how to live healthier.