Late-in-Life Interventions to Improve Cardiac Health

In a new research perspective, researchers discuss spermidine, rapamycin, caloric restriction, and exercise training to improve cardiac health in aging individuals.

Figure 1. Late-in-life exercise training boosts autophagic flux to an extent that rejuvenates cardiac function.
Figure 1. Late-in-life exercise training boosts autophagic flux to an extent that rejuvenates cardiac function.
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Cardiac dysfunction is a major public health concern. While it can occur for various reasons at any age, the prevalence of cardiac dysfunction dramatically increases with advancing age. Unfortunately, the underlying mechanisms of age-related cardiac decline are still largely unknown. Thus, it is essential for researchers to uncover novel strategies to improve cardiac health at advanced ages.

Autophagic Flux

An important physiological process involved in maintaining cardiovascular homeostasis is autophagic flux. Autophagic flux is the process by which cells break down and recycle their own cellular components after they have become damaged or unnecessary. This process is essential for maintaining healthy cardiac function, as it slows age-related oxidative damage, reduces the accumulation of toxic lipid and protein aggregates, and improves energy metabolism. However, the efficiency of autophagic flux decreases with age, resulting in declined cardiac function.

Given its crucial role and fading functioning, the search for strategies to improve autophagic flux may be essential for improving cardiovascular health as humans age. Researchers Jae Min Cho, Rajeshwary Ghosh, Sohom Mookherjee, Sihem Boudina, and J. David Symons from the University of Utah authored a new research perspective about nutraceutical, lifestyle and pharmacological interventions that can reduce age-associated cardiac dysfunction. On December 1, 2022, their research perspective was published in Aging’s Volume 14, Issue 23, entitled, “Reduce, Reuse, Recycle, Run ! : 4 Rs to improve cardiac health in advanced age.”

“In the following sections we review evidence that age-associated cardiac dysfunction can be Reduced by boosting cardiomyocyte autophagy (i.e., the ability to Reuse and Recycle damaged/dysfunctional proteins) via spermidine, rapamycin, and caloric-restriction. In addition, we highlight a new report indicating that a physiological intervention i.e., Running, rejuvenates cardiomyocyte autophagic flux to an extent that lessens age-associated cardiac dysfunction.”

Late-in-Life Interventions

Late-in-life interventions to improve cardiac health are particularly important since many of the world’s elderly populations are reaching advanced age with limited resources. This means that proven, inexpensive and accessible interventions to reduce cardiac dysfunction may have a profound impact on these populations. In this research perspective, the authors discuss four key interventions that reduce age-associated cardiac dysfunction: spermidine, rapamycin, caloric restriction, and exercise training. These interventions can reduce age-associated cardiac dysfunction by improving cardiac autophagy.

In October 2021, Cho et al. published a novel research paper about their study on late-in-life treadmill training in mice and its impact on autophagy, protein aggregates and heart function. The results of this study provided the first evidence that late-in-life exercise training can rejuvenate autophagic flux, clear protein aggregates and attenuate aging-associated cardiac dysfunction. In another murine study, researchers demonstrated that calorie restriction activates AMPK and increases the expression of autophagy-associated genes in the heart muscles.

Spermidine is a polyamine found in certain foods, such as legumes and nuts. A 2016 study linked spermidine to reduced age-associated cardiac dysfunction by attenuating cardiac hypertrophy and preserving diastolic function. Rapamycin is an mTOR inhibitor, immunosuppressant and anti-cancer drug. In a 2013 study, Flynn et al. were the first to report the cardiovascular effects of rapamycin in the context of aging. Rapamycin’s cardiovascular benefits include repressed pro-inflammatory signaling in heart muscles, reduced hypertrophy and preserved systolic function.

Conclusion

As the world’s population continues to age, it is increasingly important to identify interventions that can reduce age-associated cardiac dysfunction while avoiding high costs and potential side effects. In this research perspective, the researchers discussed evidence that spermidine, rapamycin, calorie restriction, and exercise training can improve autophagic flux and reduce age-associated cardiac dysfunction. While the mechanisms responsible for these improvements have yet to be fully elucidated, these strategies are cost-effective, accessible and relatively safe for elderly populations, and could provide a valuable way to improve cardiac health in advanced age.

“Findings from Cho et al. suggest that age-associated cardiac dysfunction can be re-established by Reducing (physical inactivity), Reusing (lysosomal degradation products e.g., amino acids for ATP synthesis), Recycling (damaged intracellular organelles via the lysosome and other protein degradation pathways), and Running (or increasing physical activity via any mode that can be enjoyed regularly and safely by the individual) (Figure 1).”

Click here to read the full research perspective published by Aging.

Aging is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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TRENDING WITH IMPACT: EFFECTS OF EXERCISE ON AGING

Researchers surveyed available literature related to exercise and its association with longevity and aging. This extensive review expands on exercise as a lifestyle intervention and its ability to counteract cellular and tissue aging.

Figure 4. Conceptual overview. Created in BioRender.

The Trending with Impact series highlights Aging publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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Regular physical exercise provides benefits for both the body and mind, but how exactly does this healthy habit benefit our cells, signaling pathways, organs, and even bones? Furthermore, how can we employ regular exercise as part of an anti-aging strategy to extend our healthspan and lifespan?

Two researchers from the Beta Cell Aging Lab at Harvard Medical School authored a recent review paper which breaks down the currently available research on this very topic, with a special focus on pancreatic beta-cells and Type 2 diabetes. The authors detailed the recorded effects of exercise at systemic and cellular levels, its effects on each of the hallmarks of aging, and a potential molecular regulatory node that may integrate those effects. This review was published in May of 2021 by Aging, and entitled: “Effects of exercise on cellular and tissue aging.”

THE NINE HALLMARKS OF AGING

With age, cellular functions and systems in the human body progressively decline and destabilize, which eventually leads to disease and all-cause mortality. There are nine hallmarks of aging, which are classified as either primary, secondary, or integrative: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. 

“Exercise is a promising lifestyle intervention that has shown antiaging effects by extending lifespan and healthspan through decreasing the nine hallmarks of aging and age-associated inflammation.” 

The researchers in this review explain that exercise is capable of counteracting each of these hallmarks of aging at systematic and cellular levels. They used publicly available research to cite and discuss the effects of exercise in each hallmark of aging in clear and thorough detail. The purpose of this article is to summarize this review, though readers are highly encouraged to read the full paper for deeper insights. 

“The literature was surveyed on MEDLINE through freely accessible PubMed as a search engine for the terms: ‘exercise’, ‘longevity’ and ‘aging’; the most relevant studies were included as they related to the 9 hallmarks of aging.”

AMPK AS A CENTRAL REGULATOR

“In summary, exercise attenuates all hallmarks of aging through different molecular pathways and effectors that seem independent and disconnected.” 

Given that exercise regulates each of these hallmarks individually, the researchers hypothesize that there must exist some kind of molecular regulatory node(s) capable of coordinating these responses. They propose that the 5’ adenosine monophosphate-activated protein kinase (AMPK) enzyme/protein could play this role.

“In summary, AMPK activation through exercise can impact all the hallmarks of aging through different signaling pathways as summarized in Figure 2 and can act as a signaling node capable of orchestrating many of the effects of exercise on the health span of different tissues and organs.”

EXERCISE AND TYPE 2 DIABETES

The researchers also discuss the effects of exercise on Type 2 diabetes mellitus (T2D). 

“In summary, exercise activates molecular signals that can bypass defects in insulin signaling in skeletal muscle and increase skeletal muscle mitochondria, which are associated with improved insulin sensitivity in skeletal muscle and therefore improve aging-associated effects of T2D.”

Figure 1. Effects of exercise upon the aging process of different organs and systems. Created in BioRender.
Figure 1. Effects of exercise upon the aging process of different organs and systems. Created in BioRender.

CONCLUSION

“We propose that future studies should address the effects of exercise on tissues which are not considered its direct targets but do show accelerated aging in T2D, such as pancreatic β-cells. In these, the role of AMPK and its physiological control will become especially significant as exercise is considered a cellular antiaging strategy.”

Click here to read the full review, published by Aging.

Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

For media inquiries, please contact [email protected].

Trending with Impact: Epigenetic Age Decreased in Diet & Lifestyle Study

Researchers conducted an eight-week study on diet and lifestyle among a small cohort of 43 male participants between the ages of 50 and 72.

Happy senior couple buying fresh food at the market

The Trending with Impact series highlights Aging publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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In addition to the well-known personal and social costs of aging, the economic costs of aging are also considerably high. Research finds that investing in delaying aging is much more cost-effective than disease-specific spending. A study found that if Americans as a whole delayed their aging by 2.2 years (while extending healthspan), economic savings over 50 years could amount to a cumulative $7 trillion.

“The growing health-related economic and social challenges of our rapidly aging population are well recognized and affect individuals, their families, health systems and economies.”

Across three countries (the United States, Canada, and Israel), researchers from the Institute for Functional Medicine, American Nutrition Association, National University of Natural Medicine, Ariel University, McGill University, and the University of California, conducted a new pilot study on the effects that diet and lifestyle intervention have on aging among healthy males between the ages of 50 and 72. This research paper was published in Aging’s Volume 13, Issue 7, and entitled, “Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial.”

The Study

The researchers organized a cohort of 43 healthy adult males between the ages of 50 and 72. Half of the participants (n=21) completed an eight-week treatment program, and the other half (control group=22) received no intervention. Interventions within the treatment program included regimented diet, sleep, exercise, relaxation guidance, and supplemental probiotics and phytonutrients. Prior to the treatment program, participants were enrolled in a preliminary education week to become acquainted with the researchers’ prescribed dietary and lifestyle interventions.

“To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males.”

Diet Prescription

Researchers prescribed the participants with mostly (not entirely) plant-based diet instructions to consume measured portions of liver, eggs, dark leafy greens, cruciferous vegetables, colorful vegetables (excluding white potatoes and sweetcorn), beets, pumpkin seeds (or pumpkin seed butter), sunflower seeds (or sunflower seed butter), methylation adaptogens, berries, rosemary, turmeric, garlic, green tea, oolong tea, animal protein, and low glycemic fruit. They were prescribed two daily doses of PhytoGanix®, which is a combination of organic vegetables, fruits, seeds, herbs, plant enzymes, prebiotics, and probiotics. A daily two-capsule dose of UltraFlora® Intensive Care, containing Lactobacillus plantarum, was also prescribed.

General guidance included that participants should choose organic food products over conventional, and to consume “healthy” oils and balanced types of fat, including coconut, olive, flaxseed, and pumpkin seed oil. Participants were told to avoid consuming added sugar, candy, dairy, grains, legumes/beans, and to minimize using plastic food containers. In addition, the prescription instructed participants to stay hydrated and not to eat between 7pm and 7am.

Lifestyle Prescription

The participant exercise prescription was a minimum of 30 minutes per day for at least five days per week, at 60-80% intensity. They completed two 20 minute breathing exercises daily, using the Steps to Elicit the Relaxation Response process developed by Herbert Benson, MD. Participants were prescribed to sleep a minimum of seven hours per night.

Measuring Epigenetic Age 

“Currently, the best biochemical markers of an individual’s age are all based on patterns of methylation [5].”

To extract DNA from the participants, researchers collected saliva samples and evaluated their RNA and DNA. They used methylation kits, assays, and the Horvath DNAmAge clock to conduct genome-wide DNA methylation analysis and calculate epigenetic age (DNAmAge) at the beginning of the study, and at the end.

“Horvath’s DNAmAge clock predicts all-cause mortality and multiple morbidities better than chronological age. Methylation clocks (including DNAmAge) are based on systematic methylation changes with age.”

Conclusion

According to the Horvath DNAmAge clock, participants in the treatment group scored an average 3.23 years younger at the end of the eight-week program when compared to participants in the control group. While these findings are meaningful, additional studies with a larger cohort size, longer duration, and other human populations will be needed in order to confirm these results.

“Notably, the shorter timeframe of this study and the scale of potential reduction, while modest in magnitude, may correlate with meaningful socioeconomic benefits, and appears to have the potential to be broadly achievable.”

Click here to read the full study, published on Aging-US.com.

Click the links below for more information on corresponding author, Dr. Kara Fitzgerald:
Biological Aging Summary | Instagram | Facebook | Twitter | General Site | Younger You Program

Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

For media inquiries, please contact [email protected].

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