What a Blood Transfusion Experiment in mice can teach us about aging

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What a blood transfusion experiment in mice can teach us about aging

Written by Deep Shukla on August 13, 2022 — Fact checked by Hilary Guite, FFPH, MRCGP

Scientists transfused blood from old mice into young ones in a bid to better understand how to mitigate the effects of aging. Image credit: Buena Vista Images/Getty Images.

One of the hallmarks of aging includes senescence, a state in which cells stop growing and dividing.

A new study shows that receiving a single blood transfusion from old mice caused the aging of tissue in young mice.

Treatment of older mice with senolytic agents, which are drugs that eliminate senescent cells, before blood transfusions to young mice reduced the levels of senescence markers in young mice.

The study shows that senescence can occur not only due to wear and tear associated with aging but also bloodborne factors.

A recent paper published in Nature MetabolismTrusted Source shows that a single blood transfusion from old mice to young animals can induce senescenceTrusted Source — cellular aging — in young mice.

The identification of factors in the blood of aged animals that induce aging could help develop therapeutics that slow down aging

Study author Dr. Irina Conboy, a professor at the University of California Berkeley, told Medical News Today:

“[Our study shows that] cellular senescence is neither cell intrinsic nor a purely chronological — damage accumulation phenomenon; it can be quickly induced in 2 weeks in young animals. SenolyticsTrusted Source only partially reduce the negative effects of old blood on young cells and tissues, suggesting additional therapeutic avenues.”

Dr. Conboy added that this study further substantiates the role of factors in old blood in promoting aging.

Causes of cellular aging

Cells tend to respond to injury or stress by either undergoing cell death or entering a state where they stop multiplying. This state in which cells stop growing and dividing is known as cellular senescence.

In addition to external stimuli such as stress, intrinsic factors such as changes in DNA structure with aging can also cause senescence.

Upon undergoing senescence, cells can send signals to the immune system, facilitating their removalTrusted Source by immune cells.

A gradual decline in the ability of the immune system to remove these senescent cells occurs with aging, resulting in the accumulation of senescent cells. The accumulation of senescent cells contributes to the aging of organs and is associated with chronic diseases.

Senescent cells can also secrete molecules that signal neighboring cells to also undergo senescence. These molecules secreted by senescent cells, known as the senescence-associated-secretory phenotype (SASP), include pro-inflammatory proteins and other factors that remodelTrusted Source the neighboring tissue.

However, the influence of these factors secreted by senescent cells in promoting aging is not well understood.

Evidence from previous studies suggests that molecules or cells present in older animals can induce tissue in younger animals to undergo aging.

For instance, studies have shown that surgically joining a young mouse with an older one can rejuvenate the tissue in the older mouse. At the same time, this procedure results in the aging of the tissue in the younger animal.

Besides having a common circulatory system, the surgically joined animals also share organs and are exposed to a similar environment. This makes it hard to single out the potential source of the pro-aging or rejuvenating factors.

Likewise, blood transfusion from aged mice to younger mice can cause tissue in the younger animal to age. These studies suggest that certain factors present in the blood of older mice can induce aging in their younger counterparts. However, whether these pro-aging effects of old blood are due to senescent cells is not known.

In the present study, the researchers examined whether senescence could be transferred from older mice to younger ones through blood transfusions.

Blood transfusions and senescence

To assess the ability of old blood to induce senescence, the authors transfused blood from aged mice (22-24 months) to their younger counterparts (3 months). The control group consisted of young rats (3 months) receiving blood transfusions from other young rats of the same age.

At 14 days after receiving the blood transfusion, the young mice receiving blood from the older mice showed increased expression of senescence biomarkers in the muscle, kidney, and liver. However, such an increase in the levels of senescence markers was absent in the lungs, heart, and brain.

The young mice that received blood transfusions from older mice also showed deficits in tasks assessing muscle strength and exhibited lower physical endurance.

Similar to skeletal muscle tissue, young mice receiving blood from older mice also showed elevated levels of biomarkers for tissue damage and impaired or suboptimal function in the liver and the kidney.

The researchers also transfused blood from younger mice to older mice and found that receiving young blood decreased tissue damage in the liver, kidney, and muscles of old mice.

In sum, these results suggest induction of senescence in young mice after receiving blood transfusions from older mice. Moreover, senescence induced in young animals after receiving blood from old mice was tissue-specific.

The effects of senolytics

The researchers then investigated whether the elimination of senescent cells in aged mice could prevent the induction of senescence in young mice after blood exchange.

For this experiment, the researchers maintained the older mice on a regimen of senolytic drugsTrusted Source that eliminate senescent cells for around 4-6 weeks. As expected, treatment with the senolytic drugs reduced the levels of secreted factors associated with senescence in the plasma of the old mice.

The researchers then transfused blood from older mice treated with either senolytic drugs or a vehicle to young mice.

Young mice receiving blood from older mice treated with senolytics showed reduced expression of senescence markers in the muscle, liver, and kidneys than young mice receiving vehicle-treated old blood.

Treatment with senolytics also attenuated the decline in liver, muscle, and kidney function and reduced the damage to these organs in young mice receiving old blood.

Moreover, administration of senolytics to older mice also reduced the adverse effects of old blood on physical activity levels and energy balance in young mice.

Young mice receiving blood from older mice treated with senolytic drugs also showed lower levels of proteins associated with inflammation, a hallmark of senescence.

However, young mice receiving blood from senolytic-treated old mice did show some negative effects associated with the transfusion of old blood. For instance, the administration of senolytics to old mice before the blood transfer failed to prevent some of the negative effects on kidney function in young mice.

These experiments show that the clearance of senescent cells in older mice attenuated the pro-aging effects of the transfer of old blood to young mice. In other words, besides being caused by stress or aging, senescence can also occur due to exposure to factors present in old blood.

Further research is necessary to identify the factors — such as molecules, organelles, or senescent cells themselves — present in the blood that were responsible for the induction of senescence in young mice.

Senescent cells secrete a number of signaling molecules in the circulation and these molecules might, at least in part, be responsible for the induction of senescence. The identification of these factors could help develop therapeutics to retard the aging process.

Study implications

Dr. James Kirkland at the Mayo Clinic Kogod Center on Aging told us:

“[This is an] interesting study that supports the effectiveness of senolytics in alleviating age-related dysfunction. It confirms and extends previous findings that transplanting senescent cells from old into young animals causes dysfunction and that removing those senescent cells from the transplanted mice restores function as well as the finding that transplanting hearts from old into young mice causes the spread of senescence and dysfunction in the young mice while transplanting hearts from young into young mice does not.”

The results of this study raise several interesting questions about aging and potential treatments for slowing down the aging process.

Dr. Stefan Tulius, director of the Transplant Surgery Research Laboratory at Brigham and Women’s Hospital noted that “[a]s any great scientific contribution, this study raises many open questions in addition to providing us with a most relevant aspect on an improved understanding of aging and the potential of increasing health life-span.”

“Those open questions relate particularly to the clinical relevance of the predominantly experimental findings: How much blood will need to be transferred to observe effects? Will a single human blood transfusion make a difference, or will the blood exchange need to go significantly beyond that? For how long will the effects last? Will they be reversible and ‘only’ temporary?”

“The authors report on changes that included long-lasting end-organ damage with scarring in livers and kidneys,” Dr. Tulius added.

“Understanding the mechanisms involved in this process may be most interesting and revealing. Interestingly also, functional effects including compromised physical activities have been observed in mice. Will those be long-lasting or just temporary? Moreover, if physical capacities are compromised, can we then also expect cognitive compromises? Indeed, the authors present fascinating findings raising many intriguing open questions that may guide us to understand aging better and to develop novel approaches facilitating healthy aging,” he went on to note.

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Biology / BiochemistrySeniors / AgingComplementary Medicine / Alternative Medicine

MEDICAL MYTHS

Medical myths: All about aging

In the latest installment of our Medical Myths series, we tackle myths associated with aging. Because aging is inevitable and, for some people, frightening, it is no surprise that myths abound.

Written by Tim Newman on September 7, 2020 — Fact checked by Anna Guildford, Ph.D.

In our Medical Myths series, we approach medical misinformation head on. Using expert insight and peer reviewed research to wrestle fact from fiction, MNT brings clarity to the myth riddled world of health journalism.

Addressing the “inevitabilities” of aging.

Around 300,000 generations ago, the human species split from an ancient ancestor that we share with chimpanzees. Since then, human life expectancy at birth has doubled.

Over the last 200 years, life expectancy at birth has doubled again. As animals go, humans perform well in longevity.

According to the World Health Organization (WHO), “Between 2000 and 2050, the proportion of the world’s population over 60 years will double from about 11% to 22%Trusted Source.”

With these facts in mind, dispelling the many myths associated with aging seems more pressing than at any point in our evolutionary history. In this article, we will tackle myths associated with exercise, cognitive ability, sex, and more.

1. Physical deterioration is inevitable

This is not entirely untrue. As we age, our body does experience wear and tear from decades of use. However, physical deterioration does not have to be complete, and people can often slow it down.

As the WHO explain, “Increased physical activity and improving diet can effectively tackle many of the problems frequently associated with old age.” These problems include reduced strength, increased body fat, high blood pressure, and reduced bone density.

Some research suggests that merely expecting physical deterioration increases the likelihood that someone will physically deteriorate.

In one studyTrusted Source, scientists surveyed 148 older adults about their aging, lifestyles, and general health expectations.

They concluded that expectations regarding aging “play an important role in the adoption of physically active lifestyles in older adults and may influence health outcomes, such as physical function.”

So, although some deterioration is likely, managing expectations will help individuals make better life choices to maintain physical health and fitness later in life.

An older study investigated how perceptions of aging influenced an individual’s likelihood of seeking medical attention. The authors of the study, which included data from 429 older adultsTrusted Source, concluded:

“[H]aving low expectations regarding aging was independently associated with not believing it important to seek health care.”

Another studyTrusted Source looked at individual attitudes to aging during late middle-age and how they might influence their overall lifespan. The authors concluded that “older individuals with more positive self-perceptions of aging, measured up to 23 years earlier, lived 7.5 years longer than those with less positive self-perceptions of aging.”

In short, keeping active, eating right, and maintaining a positive outlook can often slow the physical deterioration associated with older age.

2. Older adults should not exercise

From the previous section, it is clear that this is a myth. According to an older article in Neuropsychobiology, keeping active can boost muscle strength, reduce fat, and improve mental health.

Some people think that, once they reach a certain age, there is no point in exercising, as they believe that it will provide no benefit. This is another myth. In one studyTrusted Source, researchers put 142 adults aged 60–80 through a 42-week weight-lifting regime.

The scientists found that the course increased “dynamic muscle strength, muscle size, and functional capacity.”

There is also good evidence that regular exercise can reduce the risk of developing Alzheimer’s disease and other forms of dementia. A study, which involved 1,740 older adults, found that regular exercise was “associated with a delay in onset of dementia and Alzheimer’s disease.”

However, people should consult their doctor before embarking on a new exercise regime if they have a medical condition. For example, the National Health Service (NHS) in the United Kingdom indicate that people with certain conditions associated with age, such as osteoporosis, should avoid high impact exercise.

However, the vast majority of older adults can indulge in some form of physical activity.

3. Older adults need less (or more) sleep

Some people believe that older adults need more sleep than younger adults, perhaps because of the stereotype that older people enjoy a nap. Others say that older adults need less sleep, which might stem from the stereotype that older adults rise early in the morning.

These myths are relatively difficult to unpick because there are many factors involved. It is undoubtedly true that older adults have more difficulty getting to sleep and that their sleep tends to be more fragmentedTrusted Source.

This might help explain why some older adults need to nap in the day. As the human body changes with age, it can disrupt the circadian (daily) rhythms.

This, in turn, can impact sleep. The relationship is multifaceted, too: if a person’s circadian rhythms become disrupted, it can influence other aspects of their physiology, such as hormone levels, which might also impact their sleep.

Aside from circadian disruptions, certain diseases that occur more commonly in older adults, such as osteoarthritis and osteoporosis, can cause discomfort, which might adversely influence an individual’s ability to get to sleep or stay asleep.

Similarly, some conditions cause shortness of breath, including chronic obstructive pulmonary disease (COPD) and congestive heart failure; this can also make sleeping more challenging.

According to an older articleTrusted Source, certain medications, including beta-blockers, bronchodilators, corticosteroids, decongestants, and diuretics, can also interfere with sleep. Older adults are more likely to be taking these types of medication, sometimes together.

The Centers for Disease Control and Prevention(CDC)Trusted Source state that people aged 61–64 need 7–9 hours, and people aged 65 or older need 7–8 hours of sleep each night. It just might be more difficult for them to get that all-important shut-eye.

As a silver lining, some research suggests that older adults can handle sleep deprivation better than young adults. A study in the Journal of Sleep ResearchTrusted Source found that older adults scored better following a sleep deprivation intervention than younger adults in a range of measures, including negative affect, depression, confusion, tension, anger, fatigue, and irritability.

4. Only women get osteoporosis

Osteoporosis is a condition where bones gradually become weaker. Some people believe that it only affects women. This is not true; it can affect either sex and people of any age. However, osteoporosis is indeed much more common in older people, white people, and females.

According to an overview articleTrusted Source, the International Osteoporosis Foundation estimate that globally, around 1 in 3 women over 50 have osteoporosis, and about 1 in 5 men will experience a bone fracture related to osteoporosis in their lifetime.

Another related myth is that osteoporosis is inevitable for women as they age. As the figures above attest, two-thirds of women over 50 do not have osteoporosis. To minimize risks, the National Institute on AgingTrusted Source advise people to eat foods rich in calcium and vitamin D and exercise regularly.

5. As you age, your brain slows

The term cognitive decline refers to a gradual decrease in mental functioning with age, but before we tackle the facts of the matter, we dismiss a couple of associated myths:

Dementia is inevitable as you age

According to the WHO, the risk of developing dementia increases with age, but it does not affect all older adults. Worldwide, an estimated 5–8%Trusted Source of people over 60 have dementia. That means that 92%–95% of people aged 60 or older do not have dementia.

In the United States, an estimated 13.9%Trusted Source of people over 71 have dementia, meaning that 86.1% of people over 71 do not have dementia.

Cognitive decline leads to dementia

Contrary to popular opinion, cognitive decline does not necessarily signal the start of dementia.

People who go on to develop dementia tend to experience cognitive decline first. However, not everyone who experiences cognitive decline will develop dementia.

One older studyTrusted Source estimated that 22.2% of people in the U.S. aged 71 or older experience cognitive decline. Of these, each year, 11.7%–20% develop dementia.

Cognitive decline is inevitable

As the above statistics show, cognitive decline is not inevitable, regardless of the long-held myth that older adults experience a mental slowing down. And, importantly, there are ways to reduce the risk.

In 2015, the Alzheimer’s Association evaluated the evidence of modifiable risk factors for both dementia and cognitive decline. Their reportTrusted Source, presented to the World Dementia Council, explains that “there is sufficient evidence to support the link between several modifiable risk factors and a reduced risk for cognitive decline.”

They identified that maintaining regular physical activity and managing classic cardiovascular risk factors, such as diabetes, obesity, smoking, and high blood pressure were strongly associated with a reduced risk of cognitive decline.

They also found good evidence that a healthful diet and lifelong learning or cognitive training also reduce the risk of cognitive decline.

6. There’s no point giving up smoking now

Whether this is a genuine myth or merely an excuse, some older adults say that there is no point in giving up smoking at “their age.” This is not true. As the NHS clearly explain:

“No matter how long you have smoked for and no matter how many cigarettes you smoke a day, your health will start to improve as soon as you quit. Some health benefits are immediate, some are longer-term, but what matters is that it’s never too late.”

7. Sex is rare or impossible as you age

Some people believe that older adults lose their ability to enjoy sex and that their sexual organs become unfit for purpose. This, thankfully, is a myth.

It is true that the risk of erectile dysfunction (ED) and vaginal dryness increases as people age, but for most individuals, these are not insurmountable problems.

Sildenafil (Viagra) and lubricants or hormone creams can work wonders in many cases. Before taking Viagra, though, it is essential to speak with a doctor, as it is not suitable for everyone.

An article in the International Journal of Clinical PracticeTrusted Source indicates that around 0.4% of men aged 18–29 experience ED, compared with 11.5% of men aged 60–69. However, flipping that statistic on its head makes it much less daunting — almost 9 out of 10 men in their 60s do not have ED.

Intercourse between older people may be less fast and furious, but that is not necessarily a bad thing. As one author writes, “Growing old does not necessarily discontinue a healthy sexual life, but it does call for redefining its expression.”

There are certain benefits, too. For instance, a male’s penis often becomes less sensitive, helping them maintain an erection longer.

It is true that as some people grow older, they do not have the same sexual desire or drive as when they were young, but this is by no means the case for everyone.

To end this section on a high, below is a quote from a survey study that involved 158 older adults. Although the participants reported that they were having less sex than a decade earlier, the authors write:

“A remarkably robust sex life was evidenced by both the men and the women, even until advanced old age.”

The takehome

Overall, most of the myths surrounding age seem to center on inevitability. People believe that it is inevitable that they will gradually crumble into dust as their lives become increasingly unbearable, boring, passionless, and painful.

Although certain aspects of health might decline with age, none of the above is inevitable for everyone. As we have discovered, a positive psychological outlook on aging can benefit the physical aspects of aging.