Turning The Hourglass Sideways

Science is challenging the notion that aging is an inescapable fact of life. Here are six strategies that have been shown to prolong life in model organisms, and, in some cases, even humans.

AsianScientist (Aug. 15, 2018) – The fountain of youth; the elixir of life; the philosopher’s stone. Myths of places and items that slow down or stop the relentless forward march of aging have sprung up over millennia, evidence of humankind’s undying desire to remain forever young.

Quests for eternal youth endure to this day, but they no longer entail oceanic voyages or the perusal of mystical texts. Rather, the search has turned inward—the systematic study of biology in model organisms and humans is yielding insights into the processes involved in aging, potentially showing us how we may avoid shuffling off the mortal coil.

Here are six strategies being investigated by scientists to hold off aging and increase longevity (though not all have been proven to be effective in humans—yet).

1. Eating fewer calories

In what might seem like an ironic twist, more people are dying today from over-nutrition than under-nutrition. According to a study in The Lancet, in the 1990s, undernutrition was the leading cause of disease burden worldwide, while obesity came in at tenth place. By 2010, however, under-nutrition was ranked eighth, while obesity had climbed to sixth place.

Caloric restriction, where one’s daily nutritional intake is reduced by 20 to 30 percent, has been shown to extend lifespan in many organisms, ranging from the humble nematode worm to monkeys and even humans.

In caloric restriction experiments, rhesus monkeys lived up to 40 years of age, beyond their typical 26 years in captivity. Similar caloric restriction experiments have been performed in humans. For example, the second phase of the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE-II) trial in the US involved 238 individuals put on a 25 percent calorie-restricted diet for up to two years. The researchers observed improvement in proxy indicators of longevity such as body fat composition, glucose tolerance and cardiovascular system function in trial subjects.

2. Good ol’ exercise

Exercise has consistently been found to have positive effects on aging and health. One study analyzing data from 654,827 individuals reported that physical activity amounting to 75 minutes of walking per week was associated with an increase in life expectancy by 1.8 years. Scientists have since uncovered several mechanisms by which exercise helps maintain the normal functioning of organ systems.

For one, exercise triggers a stress response in cells resulting in the production of antioxidants that scavenge or neutralize reactive oxygen and nitrogen species. By lowering the levels of free radicals in the body, the likelihood of oxidative damage to DNA and protein constituents of cells is reduced, thus averting a range of diseases, many of which are associated with aging. In addition, exercise induces cells to generate more mitochondria—structures inside our cells that are critical for normal energy metabolism.

While the positive physiological impacts of exercise are many, much is still debated about the type, intensity and duration of exercise that can optimally prolong life in humans.

3. A re-purposed pill

If forgoing hearty meals and working out do not sound like the most appealing of methods to achieving longevity, then popping a pill might be an ideal alternative. Drug candidates that may stave off aging have surfaced in recent years, many of them acting on our body’s metabolic pathways.

Metformin, which has been prescribed for more than half a century to patients suffering from type 2 diabetes, is considered to be one of the most promising candidates for a life-extending drug. It modifies glucose metabolism, with beneficial effects on multiple organ systems that could result in a longer lifespan.

The Targeting Aging with Metformin (TAME) trial currently being conducted in the US will enroll 3,000 individuals over at least five years to investigate whether prolonged use of metformin prevents myriad aging-related diseases. (Read more about metformin and other potential anti-aging pills here.)

4. Young blood

The old and infirm may gaze upon the young with envy, lamenting their own loss of vitality. But what if youth and health were transferable? Experiments in rodents have revealed that such a notion may in fact be possible.

In a Frankenstein-esque procedure known as parabiosis, researchers sewed together the bodies of an old mouse and a young mouse, while keeping the two experimental subjects alive. When the mice healed, their circulatory systems became intertwined, and their blood mixed.

Encouragingly, the old mice were rejuvenated by the influx of young blood, exhibiting better muscle tone and liver function as well as improved cardiovascular health.

Researchers hypothesize that certain factors present in young blood help activate and sustain stem cells—cells required for the repair of worn or damaged tissues and organs—in the old mice, resulting in a more youthful constitution. The search is underway to identify these factors so that anti-aging effects can be replicated in humans sans parabiosis or frequent blood transfusions.

5. Cellular spring cleaning

“Out with the old, in with the new,” is another strategy that scientists have considered for increasing lifespan. Each organ in the body is a composite of young and old cells, as well as cells that have been damaged. Cells that are old or damaged are referred to as senescent—these cells no longer divide or self-renew.

As we age, the accumulation of senescent cells results in a decline in organ function. Senescent cells have also been shown to promote the onset of age-related diseases such as arthritis and malignant cancers.

Some candidate compounds such as quercetin and navitoclax have been identified for their ability to slow down senescence. In mice, they destroyed old and damaged cells while leaving younger, healthy cells unscathed. However, it remains to be seen whether these drugs can increase lifespan in monkeys and humans.

6. Go with your gut

The cells that make up our bodies are outnumbered by the bacteria that live in and on us. Collectively known as the microbiome, these microscopic organisms are increasingly recognized as key mediators of human health. For example, bacteria in the intestinal tract play important roles in liberating nutrients from food and controlling appetite, among other diverse functions.

Is there a link between the microbiome and longevity? One hint is that the microbiome in humans changes with age. Another comes from a study that examined 24 centenarians (individuals aged 105-109 years), revealing a unique microbiome composition in the extremely longlived. While these observations suggest a relationship between the microbiome and longevity, it is unclear whether specific strains of bacteria directly cause an increase in human lifespan.

Experiments in fish, on the other hand, have hinted at a causal link between the gut microbiome and increased lifespan. When researchers transferred gut bacteria from young African turquoise killifish into older ones, the median survival for the older fish increased by nearly 40 percent compared to controls that did not receive bacteria from young donors. The results suggest that the gut microbiome of the young fish was directly responsible for life extension in their older recipients.

This article was first published in the July 2018 print version of Asian Scientist Magazine.
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Copyright: Asian Scientist Magazine; Illustration: Maxim Usik/Asian Scientist Magazine.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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Jeremy received his PhD from Nanyang Technological University, Singapore, where he studied the role of the tumor microenvironment in cancer progression.

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