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16.8: Glycoproteins and Human Health - Biology

16.8: Glycoproteins and Human Health - Biology


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We’ll close this chapter with a few examples of glycoproteins that play crucial roles in human physiology. The major A, B, AB, O and Rh blood groups result from the presence or absence of glycoprotein antigens embedded in red blood cell membranes and the presence or absence in the blood, of antibodies against the antigens. Typically, exposure to antigens (foreign substances like bacteria, viruses, toxins…) generates immunoglobulins, the antibody molecules of our immune system; immunoglobulins are glycoproteins. The situation with blood groups is something of a paradox. The blood group antibodies already in the blood of a healthy person are not a response to foreign antigen invasion

You probably know that these blood groups must be compatible for a successful blood transfusion. A mismatch between donor and recipient can be devastating. The interaction of the red cell antigens of one blood group with antibodies in another blood group will cause the red cells to clump, restricting blood flow and ultimately killing the transfusion recipient. The table below summarizes why transfusions with mismatched A, B, AB, O blood groups must be avoided.

Group AGroup BGroup ABGroup O
Cell-surface antigens
Antibodies inthe blood

None

Acceptable donor-recipient matchesGroup A or Group O donorsGroup B or Group O donorsUniversal Recipient (Group AB, A, B, O donors)Only Group O donors
Why red cells clump in mismatched bloodAnti-A from Group B donor binds, aggregates recipient red cells; recipient Anti B binds, aggregated donor red cellsAnti-B from Group A donor binds, aggregates recipient red cells; recipient Anti A binds, aggregates donor red cellsAntibodies in Group O blood will bind any donor red cell antigens and cause the cells to clump

Another red blood cell antigen is the Rh factor. People have either it (Rh+ ) or not (Rh- ). In contrast, when an Rhrecipient receives blood from an Rh+ donor, the recipient’s immune system makes defensive anti-Rh antibodies in the usual way. This too can cause blood cell clumping with bad consequences. A word to the wise: it’s a good idea to know your own blood group!

Check the Red Cross website (here) or Wikipedia for more detail about blood groups.

The last example here involves the cell surface major histocompatibility complex (MHC) glycoproteins that distinguish self from non-self in body tissues and organs. Major organ Transplantation (liver, kidneys, heart) from donors into patients with failing organs has become, if not routine, then at least increasingly common. Before a transplant, MHC tissue typing determines donor and recipient compatibility, reducing the chances of the rejection of the transplanted organ. Since available donors are few, and good matches even fewer, patients wait on prioritized lists for a matched organ. Even when MHC typing is a match for a patient, the immune systems of transplant recipients are suppressed with hormones to reduce further the chance of rejection. Unlike the limited number of blood groups, many MHC proteins are analyzed to determine a match. Thus, it is not practical (or routinely necessary) to ‘know’ your MHC type!
In the next chapter, we look at membrane functions intrinsic to cellular existence itself.


What Glycoproteins Are and What They Do

A glycoprotein is a type of protein molecule that has had a carbohydrate attached to it. The process either occurs during protein translation or as a posttranslational modification in a process called glycosylation.

The carbohydrate is an oligosaccharide chain (glycan) that is covalently bonded to the polypeptide side chains of the protein. Because of the -OH groups of sugars, glycoproteins are more hydrophilic than simple proteins. This means glycoproteins are more attracted to water than ordinary proteins. The hydrophilic nature of the molecule also leads to the characteristic folding of the protein's tertiary structure.

The carbohydrate is a short molecule, often branched, and may consist of:

  • simple sugars (e.g., glucose, galactose, mannose, xylose)
  • amino sugars (sugars that have an amino group, such as N-acetylglucosamine or N-acetylgalactosamine)
  • acidic sugars (sugars that have a carboxyl group, such as sialic acid or N-acetylneuraminic acid)

What Are the Functions of Glycoproteins?

Glycoproteins are a form of protein that contain sugar residue. Glycoproteins are usually found at the surface of cells and assist with important processes in the body.

Glycoproteins are a form of protein that contains sugar residue. The different characteristics of sugar may change so that it attaches itself to a characteristic of the protein. Glycoproteins depend on sugar to function properly. Sugar helps them reach their destination in the organism of the cell. They play an important role in the body at the cell level. Glycoproteins are usually found at the surface of cells. Here, they work as membrane proteins sometimes facilitating some of the body's important processes like reproduction. There are three different types of glycoproteins that are determined differentiated through their synthesis mechanism and structure. These glycoproteins are either N-linked, O-linked or non-enzymatic glycoproteins.

Understanding How Glycoproteins Work in the Body Glycoproteins aid in the development of tissue function when they adhere to the cells found in the body. Glycoproteins are found in connective tissues, cell walls and blood plasma. Depending on where they are located in the body, they will display structural differences. Glycoproteins play a major role in reproduction since they are located on the surface of sperm. Glycoproteins change the plasma membrane permeability making it easier for the attraction of eggs to the sperm cells.

N-linked Glycoproteins These types of glycoproteins are modified and synthesized inside the membrane organelles of a cell. The protein part of the glycoprotein is created on the surface by other amino acids. This creates a linear polymer chain of amino acids called a polypeptide. At least 20 different types of amino acids are used to create polypeptides. The order of the amino acids in the polypeptide chain is crucial to its function. This order is called the amino acid sequence. The import of this is found when one considers that if the amino acids were ordered in a different sequence, they would not have the same function.

Some of these N-linked glycoproteins contain carbohydrates. Carbohydrates do not attach themselves to polypeptides one at a time. Instead, carbohydrates that contain many different types of sugar residues attach to the translated protein. The carbohydrates that are inside the glycoprotein are modified by enzymes that also takes away some of the sugars. It then attaches other sugars so that it forms new glycoproteins.

O-linked Glycoproteins These types of glycoproteins are created by adding sugar to the hydroxyl chain and polypeptides. They are different from the N-linked glycoproteins because they are made by the addition of sugar one type at a time. O-Linked glycoproteins often become part of an extracellular matrix after it is secreted by the cell. This extracellular matrix surrounds the O-linked glycoproteins.

Non-enzymatic Glycoproteins This creates glycoproteins when sugar is added to polypeptides in a process called glycosylation. The concentration of sugar and time control glycosylation. People, who have higher amounts of circulating glucose, experience higher levels of glycosylation. Additionally, older proteins also have a higher incidence of glycosylation. This is the primary basis of the glycosylated hemoglobin diagnostic test that is used for checking on the blood sugar levels for diabetics. It is also used for their long-term maintenance and monitoring.


Antibodies Against Abnormal Glycoproteins Identified as Possible Biomarkers for Cancer Detection

Scientists have found that cancer patients produce antibodies that target abnormal glycoproteins (proteins with sugar molecules attached) made by their tumors. The result of this work suggests that antitumor antibodies in the blood may provide a fruitful source of sensitive biomarkers for cancer detection. The study, supported in part by the National Cancer Institute (NCI), part of the National Institutes of Health, appears in the Feb. 15, 2010 issue of the journal Cancer Research.

"Thanks to emerging technologies such as the one used in this study, scientists have identified biomarkers based on the carbohydrate (sugar) portion of a glycoprotein that may be novel targets for early detection and diagnosis of certain cancers," said Sudhir Srivastava, Ph.D., M.P.H., chief of the Cancer Biomarkers Research Group in NCI's Division of Cancer Prevention.

An antibody is a type of protein that the body's immune system produces when it detects harmful substances called antigens. Antigens include microorganisms such as bacteria, fungi, parasites, and viruses. Antibodies are also produced when the immune system mistakenly considers healthy tissue a harmful substance. These antibodies, called autoantibodies, target a person’s own molecules and tissues. Research has shown that cancer patients sometimes make autoantibodies against their own malignant cells and tissues, as part of an immune response against their cancers. It is unclear why some cancer cells evade immune defenses. Scientists hope that such antibodies may ultimately have the potential to help doctors detect cancer by a simple blood test.

The glycoproteins that were the focus of this study are called mucins. Mucins comprise a family of glycoproteins, called O-glycoproteins, which are on the outer surface of cells and play an important role in cell-to-cell interactions. Tumors have been found to produce different types and amounts of mucins compared with normal cells and to produce mucins that have altered sugar groups.

Scientists led by Hans H. Wandall, M.D., Ph.D. and Ola Blixt, Ph.D., Center for Glycomics, Copenhagen University in Denmark, hypothesized that the abnormal molecular structures of the O-glycoproteins manufactured by cancer cells might cause patients to develop autoantibodies to them. To test this theory, the scientists had to overcome a number of challenges to develop a tool that could successfully identify autoantibodies to abnormal O-glycoproteins. The team used this approach to screen blood specimens from breast, ovarian and prostate cancer patients.

They found distinct abnormal mucin-type O-glycopeptide epitopes (parts of molecules that antibodies will recognize and bind to) that were targeted by autoantibodies in cancer patients — but such antibodies were absent in healthy controls.

Although larger sets of specimens will have to be analyzed to fully appreciate the clinical value of this technology, the preliminary results are very promising.

The study was an international collaboration that was funded in part by NCI through the trans-NIH Alliance of Glycobiologists for Detection of Cancer and Cancer Risk. The alliance is a consortium of NCI-supported tumor glycomics laboratories that are working to reveal the cancer-related dynamics of complex carbohydrates and develop biomarkers for early cancer detection and risk assessment.

Michael Hollingsworth, Ph.D., The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, and Henrik Clausen, M.D., Ph.D. Center for Glycomics, Copenhagen University, lead one of the tumor glycomics laboratories. Other scientists, from Center for Glycomics, Copenhagen University Kings College School of Medicine, Guy’s Hospital, London and the Memorial Sloan-Kettering Cancer Center, New York City, collaborated in this research.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

For more information on the Alliance of Glycobiologists for Detection of Cancer and Cancer Risk visit: http://glycomics.cancer.gov/.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH&hellipTurning Discovery Into Health ®

Reference

Clausen H, et al. Autoantibody Signatures to Aberrant O-Glycopeptide Epitopes Serve as Undiscovered Biomarkers of Cancer. Cancer Research, Feb 15, 2010. DOI 10.1158/0008-5472. CAN-09-2893.


Materials and Methods

Study Approval and Population

The collection and use of the whole saliva for research in this study were approved by the Ethical Committee of Northwest University (Xi𠆚n, China) and the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). Written informed consent was received from participants. And this study was conducted by the ethical guidelines of the Declaration of Helsinki. After a standardized endoscopic procedure and histopathological evaluation, the individuals diagnosed with primary ESCC (n 㴖) were enrolled in this study. The age- and sex-matched HVs (n = 25) were recruited from the health checkup center in the same hospital where they underwent a medical examination. All the participants had no significant differences between the two groups regarding demographic, socioeconomic, and lifestyle characteristics, and those who received preoperative radiotherapy, chemotherapy, chemoradiotherapy, or antibiotic therapy were excluded from this study. The clinical characteristics of HVs and ESCC patients were summarized in Table 1.

TABLE 1. Demographic and clinical information of ESCC patients and HV subjects in this study.

Whole Saliva Collection and Preparation

The collection protocol has been described in previous literature (Liu et al., 2018 Shu et al., 2018). The collected whole saliva was centrifuged at 10,000 g at 4ଌ for 15 min to remove insoluble components. And the cocktail of protease inhibitor (Sigma-Aldrich, United States) was added to the collected supernatant according to the manufacturer’s recommendations and lyophilized at �ଌ until use.

Lectin Microarrays and Data Analysis

The lectin microarrays were produced using 37 lectins with different binding preferences covering N- and O-linked glycans (Shu et al., 2017 Yu et al., 2020b). The Cy3-labeled glycoproteins were incubated on the lectin microarray with gentle rotation in the dark (37ଌ, 3 h). The microarrays were washed with PBST and PBS, respectively, centrifuged dry, and scanned immediately using a Genepix 4000B confocal scanner (Axon Instruments, United States). The generated images were analyzed by Gene pix software (version 6.0, Axon Instruments Inc., Sunnyvale, CA). The unsupervised average hierarchical cluster analysis (HCA) and principal component analysis (PCA) were performed by Expander 6.0 (http://acgt.cs.tau.ac.il/expander/) and Multivariate Statistical Package (United Kingdom), respectively. And the p value was derived from the nonparametric Mann–Whitney test using the GraphPad Prism software (Version 7.0, GraphPad Software, Inc., San Diego, CA).

Lectin Blotting Analysis

The expression levels of glycan structures were analyzed by lectin blotting as described previously (Zhang et al., 2019 Yu et al., 2020b). The pooled salivary protein was separated by 10% SDS-PAGE and transferred onto PVDF membrane (0.22 mm Millipore, Bedford, MA, United States). The PVDF membrane was blocked by the Carbo-Free Blocking Solution (Vector Labs, Burlingame, CA) and incubated with Cy5-labeled DSA, ECA, LCA, PSA, and UEA-I, respectively. The membrane was scanned by the STORM FluorImager (Molecular Dynamics, Sunnyvale, CA, United States) and measured using the ImageJ software (NIH).

Preparation of DSA-Magnetic Particle Conjugates

The epoxy-coated magnetic particles (2 mg) were rinsed with ethanol and coupling buffer (5 mM NaB4O7, 180 mM H3BO4, 150 mM Na + , pH 7.4), respectively, and reacted with DSA solution (DSA dissolve in coupling buffer) according to the protocol (Zhang et al., 2019 Yang et al., 2020b). Then, conjugates were washed with a coupling buffer to remove the unbound lectins.

Selective Isolation of Glycoprotein Fractions from Saliva by DSA-Magnetic Particle Conjugates

The GlcNAc and Gal㬡-4GlcNAc-containing glycoproteins were isolated from ESCC patients and HVs using DSA-magnetic particle conjugates as described previously (Zhang et al., 2019 Yang et al., 2020b). Briefly, the pooled salivary protein was diluted with the binding buffer (100 Mm Tris-HCl 150 mM NaCl 1 mM CaCl2, MgCl2, and MnCl2 pH 7.4) and incubated with the DSA conjugates (room temperature, 3 h). After 3 h gentle shaking, the conjugates were washed using washing buffer (0.1% Tween-20 in binding buffer, pH 7.2) to remove unbound proteins, and the glycoproteins bound to the conjugates were eluted with an eluting buffer (8 M urea, 40 mM NH4HCO3).

Isolation and Purification of N-Linked Glycans

The isolation and purification of N-glycans were performed based on previously described methods (Qin et al., 2017 Yang et al., 2020b). The glycoproteins were concentrated and desalted by Amicon Ultra-0.5 3 KDa ultrafiltration units (Millipore, United States) and then denatured by the addition of 8 M urea, 10 mM DTT, and 10 mM IAM. The denatured glycoproteins were exchanged to 40 mM NH4HCO3 buffer and incubated with trypsin (37ଌ, overnight). The trypsin in the mixture was inactivated by heating (80ଌ, 5 min) and then the PNGase F (New England Biolabs, Beverly, MA) was added to release the N-glycans (37ଌ, overnight). Subsequently, the digest was subjected to HyperSep Hypercarb SPE cartridges (25 mg, 1 mL Thermo Scientific) to remove peptides. The purified N-glycans were collected and lyophilized.

Characterization of N-Glycans by MALDI-TOF/TOF-MS

The N-glycans were characterized by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectroscopy (MALDI-TOF/TOF-MS, UltrafleXtreme, Bruker Daltonics Bremen, Germany) as described previously (Qin et al., 2017 Zhang et al., 2019 Yang et al., 2020b). Glycans were resuspended and spotted onto an MTP AnchorChip sample target. Then, 2 μL of 10 mg/mL 2,5-dihydroxybenzoic acid (DHB) with 1 mM NaCl in 50% (v/v) methanol solution was spotted to recrystallize the N-glycans and vacuum dried for analysis. Peptide calibration standards (250 calibration points Bruker) were used as mass calibration. Positive ion reflection mode was performed, and a mass range of 1,000𠄴,000ꃚ was analyzed. Representative MS spectra of N-glycan mass peaks with signal-to-noise ratio above three were generated and annotated using FlexAnalysis and GlycoWorkbench software.


Glycoproteins: Their Biochemistry, Biology and Role in Human Disease

A GREAT number of the proteins that are found in nature have carbohydrate covalently linked to the peptide portion and are accordingly termed glycoproteins. These conjugated proteins are represented by many substances of biologic importance, including enzymes, hormones, antibodies and membranes. The collagens, major structural proteins of the body, have now been clearly shown to belong to the glycoprotein family, and the presence of a large number of carbohydrate-containing proteins in plasma and mucous secretions has been appreciated for a long time.Increasing attention has been called to the medical importance of the glycoproteins, for they have been implicated, either . . .


Sialic Acids and Sialoglycoconjugates in the Biology of Life, Health and Disease

Sialic Acids and Sialoglycoconjugates in the Biology of Life, Health and Disease enables the reader to understand the role of sialylation as a post translational modification. The book provides insights on the latest knowledge in the field of sialoglycobiology. Sialic acids as terminal residues of oligosaccharide chains play crucial roles in several cellular recognition events. Synthesized post translationally, they play an important role in recognition, signaling, immunological response and cell-cell interaction. Improper sialylations have been associated with several diseases including cancer. In the post genomics and proteomics era, sialoglybiology has become more and more important in deciphering health and disease conditions.

Sialic Acids and Sialoglycoconjugates in the Biology of Life, Health and Disease enables the reader to understand the role of sialylation as a post translational modification. The book provides insights on the latest knowledge in the field of sialoglycobiology. Sialic acids as terminal residues of oligosaccharide chains play crucial roles in several cellular recognition events. Synthesized post translationally, they play an important role in recognition, signaling, immunological response and cell-cell interaction. Improper sialylations have been associated with several diseases including cancer. In the post genomics and proteomics era, sialoglybiology has become more and more important in deciphering health and disease conditions.


Research on intermittent fasting shows health benefits

Evidence from decades of animal and human research points to wide-ranging health benefits of intermittent fasting, according to an NIA-conducted review of the research, published in the New England Journal of Medicine. Still, more research is needed to determine whether intermittent fasting yields benefits or is even feasible for humans when practiced over the long term, such as for years.

Intermittent fasting is an eating pattern that includes hours or days of no or minimal food consumption without deprivation of essential nutrients. Commonly studied regimens include alternate day fasting, 5:2 intermittent fasting (fasting two days each week), and daily time-restricted feeding (such as eating only during a six-hour window).

Hundreds of animal studies and scores of human clinical trials have shown that intermittent fasting can lead to improvements in health conditions such as obesity, diabetes, cardiovascular disease, cancers and neurological disorders. The evidence is less clear for lifespan effects. Animal studies have shown mixed results, with sex, food composition, age and genetics among the factors that influence longevity. Human trials have mainly involved relatively short-term interventions and so have not provided evidence of long-term health effects, including effects on lifespan.

The review authors are Rafael de Cabo, Ph.D., of NIA’s Intramural Research Program (IRP), and Mark P. Mattson, Ph.D., formerly of NIA’s IRP and currently a neuroscientist at the Johns Hopkins University School of Medicine.

Although intermittent fasting often results in reduced calorie consumption, weight loss is not the main driver of the health benefits observed in preclinical and clinical studies, according to the authors. Rather, the key mechanism is metabolic switching, in which fasting triggers the body to switch its source of energy from glucose stored in the liver to ketones, which are stored in fat.

“Ketone bodies are not just fuel used during periods of fasting,” the authors wrote. “They are potent signaling molecules with major effects on cell and organ functions.”

Ketogenesis, or the increase of ketones in the bloodstream, initiates activity in a variety of cellular signaling pathways known to influence health and aging. This activity enhances the body’s defenses against oxidative and metabolic stress and initiates the removal or repair of damaged molecules. The impact of ketogenesis carries over into the non-fasting period and can improve glucose regulation, increase stress resistance and suppress inflammation.

“Repeated exposure to fasting periods results in lasting adaptive responses that confer resistance to subsequent challenges,” the authors explain. The “broad-spectrum benefits” include not only disease resistance but also improved mental and physical performance.

The authors acknowledge impediments to widespread adoption of intermittent fasting: the ingrained practice in developed nations of three meals a day plus snacks (along with the ready availability and marketing of food), the discipline required to shift to a new eating pattern and the lack of physician training on intermittent fasting interventions. The authors suggest that clinicians who prescribe intermittent fasting encourage their patients to adopt a gradual, phased-in schedule in consultation with a dietitian or nutritionist.

In addition to the question of intermittent fasting’s long-term effects in humans, the authors point to two other areas requiring further research. Studies are needed to determine whether this eating pattern is safe for people at a healthy weight, or who are younger or older, since most clinical research so far has been conducted on overweight and middle-aged adults. In addition, research is needed to identify safe, effective medications that mimic the effects of intermittent fasting without the need to substantially change eating habits.

This review article and many of the research studies cited within were supported by NIA.

Reference: De Cabo R and Mattson MP. Effects of intermittent fasting on health, aging, and disease. New England Journal of Medicine. 2019381(26):2541-2551. doi: 10.1056/NEJMra1905136.


Methods

Peptide sharing analyses have been extensively described elsewhere [16, 17]. Briefly, SARS-CoV-2 spike glycoprotein (NCBI protein primary sequence was dissected into hexa- and heptapeptides offset by one residue (i.e., MFVFLV, FVFLVL, VFLVLL, FLVLLP). We obtained 1268 hexapeptides and 1267 heptapeptides. Then each viral hexa- or heptapeptide was analyzed as a probe to scan for occurrences of the same hexa- or heptapeptide in the reference proteome from the following mammalian organisms (with taxonomy ID in parentheses): human, Homo sapiens (9606) mouse, Mus musculus (10090) rat, Rattus norvegicus (10116) cat, Felis catus (9685) dog, Canis lupus familiaris (9615) rabbit, Oryctolagus cuniculus (9986) chimpanzee, Pan troglodytes (9598) gorilla, Gorilla gorilla gorilla (9595) and rhesus macaque, Macaca mulatta (9544). Three viral proteomes were added as coronavirus controls: human coronavirus HKU1 (290028) human coronavirus 229E (11137) and human coronavirus OC43 (31631). The hexa/heptapeptide matching analyses were conducted by using Pir Peptide Matching program [18].

The expected value for hexapeptide sharing between two proteins was calculated by considering the number of all possible hexapeptides. Since in a hexapeptide, each residue can be any of the 20 amino acid (aa), the number of all possible hexapeptides N is given by N = 20 6 = 64 × 10 6 . Then, the number of the expected occurrences is directly proportional to the number of hexapeptides in the two proteins and inversely proportional to N. Assuming that the number of hexapeptides in the two proteins is << N and neglecting the relative abundance of aa, we obtain a formula derived by approximation, where the expected number of hexapeptides is 1/N or 20 −6 . By applying the same calculation, the expected value for heptapeptide sharing between two proteins is equal to 20 −7 .


Longer daily fasting times improve health and longevity in mice

Increasing time between meals made male mice healthier overall and live longer compared to mice who ate more frequently, according to a new study published in the Sept. 6, 2018 issue of Cell Metabolism. Scientists from the National Institute on Aging (NIA) at the National Institutes of Health, the University of Wisconsin-Madison, and the Pennington Biomedical Research Center, Baton Rouge, Louisiana, reported that health and longevity improved with increased fasting time, regardless of what the mice ate or how many calories they consumed.

"This study showed that mice who ate one meal per day, and thus had the longest fasting period, seemed to have a longer lifespan and better outcomes for common age-related liver disease and metabolic disorders," said NIA Director Richard J. Hodes, M.D. "These intriguing results in an animal model show that the interplay of total caloric intake and the length of feeding and fasting periods deserves a closer look."

The scientists randomly divided 292 male mice into two diet groups. One group received a naturally sourced diet that was lower in purified sugars and fat, and higher in protein and fiber than the other diet. The mice in each diet group were then divided into three sub-groups based on how often they had access to food. The first group of mice had access to food around the clock. A second group of mice was fed 30 percent less calories per day than the first group. The third group was meal fed, getting a single meal that added up to the exact number of calories as the round-the-clock group. Both the meal-fed and calorie-restricted mice learned to eat quickly when food was available, resulting in longer daily fasting periods for both groups.

The scientists tracked the mice's metabolic health through their lifespans until their natural deaths and examined them post-mortem. Meal-fed and calorie-restricted mice showed improvements in overall health, as evidenced by delays in common age-related damage to the liver and other organs, and extended longevity. The calorie-restricted mice also showed significant improvement in fasting glucose and insulin levels compared to the other groups. Interestingly, the researchers found that diet composition had no significant impact on lifespan in the meal fed and calorie restricted groups.

Mice with longer fasting times (green) and shorter times when food was available (red) had better health outcomes and longevity than mice who were allowed to eat around the clock. – Image credit NIA IRP.

According to the study's lead author, Rafael de Cabo, Ph.D., chief of the Translational Gerontology Branch of the NIA Intramural Research Program, scientists have studied the beneficial effects of caloric restriction for more than a century, but the impact of increased fasting times has recently come under closer scrutiny.

"Increasing daily fasting times, without a reduction of calories and regardless of the type of diet consumed, resulted in overall improvements in health and survival in male mice," said de Cabo. "Perhaps this extended daily fasting period enables repair and maintenance mechanisms that would be absent in a continuous exposure to food."

The researchers say their findings are encouraging for future studies on how these types of time-restricted eating patterns might help humans to maintain healthy weight and reduce some common age-related metabolic disorders. According to de Cabo, next steps for this research include expanding these findings to other strains of mice and other lab animal species using both sexes, and to find the potential translation of the findings in humans.

About the National Institute on Aging (NIA): The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. The Institute’s broad scientific program seeks to understand the nature of aging and to extend the healthy, active years of life. For more information on research, aging, and health, go to the NIA website.

About the National Institutes of Health: NIH, the nation's medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs visit the NIH website.


Watch the video: Glycoproteins - MCQ discussion (June 2022).


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