What can hold back the hands of time? Scientists have looked at these five treatments

Joanne Laucius, Ottawa Citizen 7 minute read January 30, 2020

"Gene Editing." Mike Faille / jpg

Scientists have been researching ways to increase a human’s healthspan — and possible lifespan — for decades. Here are things they have considered, and what they have learned.

The intervention: Rapamycin

What is it? First identified in the 1970s in a soil sample from Easter Island, this FDA-approved drug is used to suppress the immune system in transplant patients. Counterintuitively, it also appears to boost immune function in healthy animals. Rapamycin may reduce inflammation, which increases with age. One study found that rapamycin rejuvenated the hearts of old mice. After treatment, there were significant improvements to cardiac function. Research with mice has also found that even when they where administered rapamycin late in life, the mice still had improvements to lifespan and their healthspan.

The verdict: Geroscientist Matt Kaeberlein said rapamycin shows the most promise of any drug that targets aging, in his opinion, although he doesn’t necessarily think rapamycin will increase lifespan by 20 to 30 years on average in people. “Although it might at the right dose. I do think there’s reason to believe that rapamycin could improve several age-related health problems, including boosting immune function and protecting against dementia, cancers, and heart disease.”

But critics say it is unclear what the downstream effects could be. “If you take a compound like that for a few decades, there may be downstream effect  — a small epidemic of lymphoma, perhaps,” said geriatrician Dr. Peter Boling. While it is approved to prevent rejection in organ transplant patients, it is not approved to treat aging.

There are also questions about side effects, which may include susceptibility to infection and the possibility of developing lymphoma.

“We still don’t know about all of the hidden dangers. As hopeful as we might be, we have to be aware of the limitations,” said Boling.

The intervention: Metformin

What is it? This drug has been prescribed to millions of people to treat diabetes. Among other effects, it decreases insulin levels. It also appears to target biological mechanisms related to aging. Its anti-aging effects may be linked to its influences on metabolic and cellular processes associated with inflammation. It has been linked to lifespan extension and protection against age-related diseases in animal models.

The verdict: The speculation in scientific circles has been that many of the drugs used to treat early-stage chronic disease may be effective, at least in part, because they target aging itself.

“Metformin is an interesting case,” said Kaeberlein. It clearly increases survival in people with diabetes and likely would do the same for pre-diabetics and others with significant metabolic disease, which represents a growing percentage of adults, he said. However, it’s less clear whether metformin will be beneficial in people who are metabolically healthy and exercise regularly.

“The studies in mice suggest that metformin is different from rapamycin, in the sense that metformin only increases lifespan by a very small amount and in some cases has been reported to have no effect or even shortens lifespan in mice.”

The FDA has accepted a clinical trial, Targeting Aging with Metformin, known as TAME, which will test whether metformin can delay the onset of age-related diseases and conditions including cancer, cardiovascular disease and Alzheimer’s disease. The goal of the trial, which is estimated to cost $55 million, is not to help people live to be 120 years old but “to add health to our years,” said the American Federation for Aging Research.

“Like metformin, several promising drugs show great potential and await trials. If successful, the TAME trial would give the pharmaceutical industry impetus to advance these drugs and transform aging from a period of sickness to a time of extended vitality.”

The intervention: Caloric restriction

What is it? A dietary regimen that reduces calories while maintaining nutrients. Research in lab animals, which started almost a century ago, has shown that it is possible to delay age-related diseases in mice and rats through dietary and caloric restriction, but results have varied.

A parallel study of two groups of rhesus monkeys, one at the University of Wisconsin and the other at the U.S. National Institute on Aging, looked at the life-prolonging and health effects of a calorie-restricted diet. The researchers found that the Wisconsin monkeys on a diet with 30 per cent fewer calories than the control group survived to about 28 years for males and about 30 years for females — a couple of years above average for monkeys in captivity. Calorie-restricted monkeys in both groups showed fewer age-related health conditions compared to the control monkeys.

Some “biohackers” — people who use biological interventions to optimize health — have embarked on caloric restriction diets, with the goal of living longer. Entrepreneur Dave Asprey, author of Bulletproof Diet, has said he plans to live to be 180 and is hacking his own biology with a number of interventions, including supplements and a strict diet.

The verdict so far: The rhesus monkey study also produced some contradictory findings. The National Institute on Aging’s study found that while the dieting monkeys showed improved health, they didn’t necessarily live longer than the control monkeys. It’s not clear why there was a difference between the two groups of monkeys, although they were fed different diets and had different feeding times and access to food. The ages at which they dieted may also have come into play.

“There is no compelling evidence caloric restriction will work with people,” said Doug Gray, a molecular biologist with an interest in the role of protein homeostasis in aging and diseases of aging at the Ottawa Hospital Research Institute.

If this sounds like a depressing route to extreme longevity, even scientists agree. Noted one researcher: “Life might seem longer, but it wouldn’t necessarily be longer.”

The intervention: Gene editing

What is it? Genome editing, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced.

Last February, for example, the journal Nature Medicine reported on a therapy using CRISPR-Cas9 genome editing technology aimed at suppressing rapid aging in mice with the rare genetic disorder progeria, which causes accelerated aging. According to the report, two months after the therapy, the progeria mice were stronger and more active and had better heart health. Their lifespan also increased by about 25 per cent.

The verdict so far: Not ready for prime time, said Boling. Even though we have successfully mapped the human genome, and it’s technically possible to remove a gene sequence and replace it, we have yet to successfully edit genes in a complex organism. Many people don’t want to eat food containing genetically-modified organisms, let alone become one, he said.

“I don’t think we have a clear handle on a special gene sequence that would essentially change the aging process. I would want to see if we could do it in a limited and focused way without undue downstream consequences.”

In 2017, researchers at Stanford University medical school reported that injections of blood plasma from donors between the ages of 18 and 30 showed promise for helping human Alzheimer’s patients with mild to moderate symptoms regain some ability to perform basic daily tasks. COLLEEN DE NEVE COLLEEN DE NEVE / CALGARY HERALD

The intervention: Young blood

What is it? There have been a number of studies that looked at whether giving old mice blood from young mice could reverse some signs of aging. Even the researchers admitted it sounded creepy, but the results were intriguing. One study at the University of California, Berkeley, published in 2018, found that

old mice showed benefits, including better muscle repair, from receiving blood from young mice. But young mice who received old blood had negative effects, including performing poorly on a strength test.

In 2017, researchers at Stanford University medical school reported that injections of blood plasma from donors between the ages of 18 and 30 showed promise for helping human Alzheimer’s patients with mild to moderate symptoms regain some ability to perform basic daily tasks, such as remembering to take their medications or preparing meals. The results were based on reports from the patients and their caregivers. The researchers cautioned that more research is needed, since the trial involved only nine patients who had received plasma infusions and nine who had received a placebo saline infusion.

The verdict so far: Don’t try it. In a statement last February, the FDA said it had “significant public health concerns” about establishments that offer infusions of plasma from young donors to treat conditions ranging from normal aging and memory loss to Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, and PTSD.

“Simply put, we’re concerned that some patients are being preyed upon by unscrupulous actors touting treatments of plasma from young donors as cures and remedies. Such treatments have no proven clinical benefits for the uses for which these clinics are advertising them and are potentially harmful,” warned the FDA. “There are reports of bad actors charging thousands of dollars for infusions that are unproven and not guided by evidence from adequate and well-controlled trials.”