Identifying And Targeting Cancer Stem Cells

Here is a paper from several years ago demonstrating further identification of (colon) cancer stem cells, with information on targeting such cells for therapy.  Abstract:

The cancer stem cell (CSC) theory highlights a self-renewing subpopulation of cancer cells that fuels tumour growth. The existence of human CSCs is mainly supported by xeno-transplantation of prospectively isolated cells, but their clonal dynamics and plasticity remain elusive. Here, we demonstrate that human LGR5+ colorectal cancer cells serve as CSCs in growing cancer tissues. Lineage-tracing experiments with a CRISPR-Cas9-mediated LGR5-CreER knock-in allele reveal self-renewal and differentiation capacity of LGR5+ tumour cells. Selective ablation of LGR5+ CSCs in LGR5-iCaspase9 knock-in organoids leads to tumour regression, followed by tumour regrowth driven by re-emerging LGR5+ CSCs. KRT20-CreER marks differentiated cancer cells that constantly diminish in tumour tissues, while reverting to LGR5+ CSCs and contributing to tumour regrowth after LGR5+ CSC ablation. We also show that combined chemotherapy potentiates LGR5+ CSCs targeting. These data provide insights into the plasticity of CSCs and their potential as a therapeutic target in human colorectal cancer.

We'll be following further developments in this field.

Targeting Senescent Cells

Here is a paper from several years ago suggesting that targeting senescent cells with programmed cell death can reverse aspects of aging in mice.  Older studies suggested rapamycin or carnosine as anti-aging interventions. We will be keeping track of further developments in this field.

Yet Another Reason Not To Smoke

Tobacco pipes and car airbags don't mix, abstract:

Airbags have been shown to reduce injuries and save the lives of car occupants in a crash. Like any protection system, airbags potentially introduce some new risks if no appropriate countermeasures are taken. A case of a relatively moderate frontal impact is described where the driver of an airbag-equipped car suffered a severe penetrating eye injury after the airbag deployed. Since the airbag fabric itself was excluded as an injury-producing structure, other objects such as eyeglasses, a wrist-watch, a bracelet, and a large finger ring had to be assessed. The investigation of the car interior as well as the morphologic details of the injuries to the eye and the face revealed that the most likely candidate for the injury was a tobacco pipe, which was probably being held in one hand and was broken apart by the deploying airbag and projected into the face of the driver. This case illustrates the hazard of having any rigid object between the occupant and the deploying airbag. The desirability of warning car occupants of the potential hazards which can result from today's protection systems is also discussed.

Don't smoke.

Sweetness, Food Addiction, And Overweight: A Study Denying A Connection?

Here is a paper from several years ago that goes against "conventional wisdom" arguing that:

...sugary foods contribute minimally to 'food dependence' and increased risk of weight gain. Instead, they are consistent with the current scientific notion that food energy density, and the unique individual experience of eating, plays an important role in determining the reward value of food and promoting excessive energy intake.

I think we need to look at additional studies for conformation or refutation, considering the importance of sugar in the American diet and American obesity.  No doubt of course "high food density" is the most important thing and a combination of high fat and sweetness - indeed identified in this study as a problem - may be a particular "villain" here.

Age And Triathlon Performance

How does Ironman triathlon performance change with age?  Abstract:

In Ironman triathlon, the number of overall male and female finishers increased in the last 30 years, while an improvement in performance has been reported. Studies concluding these numbers only analysed the top ten athletes per age group instead of all finishers, therefore a selection bias might have occurred. The aim of the present study was to investigate participation, performance and the age-related performance decline of all pro and age group triathletes ranked in all Ironman triathlons held worldwide between 2002 and 2015. Split and overall race times of 329,066 (80%) male and 81,815 (20%) female athletes competing in 253 different Ironman triathlon races were analysed. The number of finishers increased in all age groups with exception of women in age group 75-79 years. In pro athletes, performance improved in all disciplines. In age group athletes, performance improved in younger age groups for running (18-24 to 40-44 years) and older age groups for swimming (50-54 to 65-69 years) and cycling (35-39 to 55-59 years), while it impaired in younger age groups for swimming (18-24 to 45-49 years) and cycling (18-24 to 30-34), and older age groups in running (45-49 to 70-74 years). The age-related performance decline started in women in age group 25-29 years in swimming and in age group 30-34 years in cycling, running and overall race time, whereas it started in men in age group 25-29 years in swimming and in age group 35-39 years in cycling, running and overall race time. For athletes and coaches, performance improved in younger age groups for running and older age groups for swimming and cycling and the age-related decline in performance started earlier in swimming than in cycling and running. In summary, women should start competing in Ironman triathlon before the age of 30 years and men before the age of 35 years to achieve their personal best Ironman race time.

It is interesting that performance in swimming declined earlier with age than in cycling and running, suggesting that swimming is the most intense exercise of the three.  The last sentence suggests that Ironman  is best for the young.

Protein Intake Timing

Here is a paper from several years ago that asserts that protein intake distribution – consuming most of the protein at one meal or spreading it out more evenly throughout the day – does not affect muscle building.  Hence the authors conclude:

We conclude that over an 8-week intervention period, the protein intake distribution pattern in mixed meals does not play an important role in determining anabolic response, muscle strength, or functional outcomes. 

One caveat is that it is uncertain whether the subjects were doing any resistance exercising. For example, you may expect to observe better results consuming a lot of protein just after the workout (and/or before and after) than distributed throughout the day, but this needs to be confirmed.  If the subjects were just regularly active, then perhaps intake time does not matter.  More study is required.

Carbs And Protein For Muscle Recovery

A paper from several years ago supports the traditional wisdom for post-workout muscle recover, abstract:

The objective of the study was to investigate whether co-ingestion of carbohydrate and protein as compared with protein alone augments muscle protein synthesis (MPS) during early exercise recovery. Two months old rats performed 10 repetitions of ladder climbing with 75% of body weight attached to their tails. Placebo (PLA), whey protein (WP), or whey protein plus carbohydrate (CP) was then given to rats by gavage. An additional group of sedentary rats (SED) was used as controls. Blood samples were collected immediately and at either 1 or 2 h after exercise. The flexor hallucis longus muscle was excised at 1 or 2 h post exercise for analysis of MPS and related signaling proteins. MPS was significantly increased by CP compared with PLA (p<0.05), and approached significance compared with WP at 1 h post exercise (p = 0.08). CP yielded a greater phosphorylation of mTOR compared with SED and PLA at 1 h post exercise and SED and WP at 2 h post exercise. CP also increased phosphorylation of p70S6K compared with SED at 1 and 2 h post exercise. 4E-BP1 phosphorylation was inhibited by PLA at 1 h but elevated by WP and CP at 2 h post exercise relative to SED. The phosphorylation of AMPK was elevated by exercise at 1 h post exercise, and this elevated level was sustained only in the WP group at 2 h. The phosphorylation of Akt, GSK3, and eIF2Bε were unchanged by treatments. Plasma insulin was transiently increased by CP at 1 h post exercise. In conclusion, post-exercise CP supplementation increases MPS post exercise relative to PLA and possibly WP, which may have been mediated by greater activation of the mTOR signaling pathway

Carbs and protein post-resistance training therefore proved here superior to protein alone.

Different Supplementation For Resistance Exercise

From several years ago, here is a paper on a specific supplementation intake regimen for resistance training. Abstract:

Lowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7): 1843-1854, 2016-Adenosine-5'-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of β-hydroxy-β-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p < 0.001). In a similar fashion, strength gains after training were increased in HMB-FA/ATP-supplemented subjects by 23.5% (p < 0.001). Vertical jump and Wingate power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3-5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who continuously train at high levels such as elite athletes or military personnel.

This may be of interest to high-intensity trainees.

Meal Delivery And Elder Feeding

Home-delivered meal programs help elder diets, abstract:

BACKGROUND:

Poor diet quality and insufficient nutrient intake is of particular concern among older adults. The Older Americans Act of 1965 authorizes home-delivered meal services to homebound individuals aged 60 years and older.

OBJECTIVE:

The purpose of this study was to review scientific evidence on the impact of home-delivered meal services on diet and nutrition among recipients.

METHODS:

Keyword and reference searches were conducted in Cochrane Library, Google Scholar, PubMed and Web of Science. Inclusion criteria included: study design (randomized controlled trials, cohort studies, pre-post studies, or cross-sectional studies); main outcome (food and nutrient intakes); population (home-delivered meal program participants); country (US); language (articles written in English); and article type (peer-reviewed publications or theses).

RESULTS:

Eight studies met the inclusion criteria, including two randomized controlled trial studies (from the same intervention), one cohort study, two pre-post studies, and three cross-sectional studies. All but two studies found home-delivered meal programs to significantly improve diet quality, increase nutrient intakes, and reduce food insecurity and nutritional risk among participants. Other beneficial outcomes include increased socialization opportunities, improvement in dietary adherence, and higher quality of life.

CONCLUSIONS:

Home-delivered meal programs improve diet quality and increase nutrient intakes among participants. These programs are also aligned with the federal cost-containment policy to rebalance long-term care away from nursing homes to home- and community-based services by helping older adults maintain independence and remain in their homes and communities as their health and functioning decline.

As families are scattered about, particularly in the USA, it is important that some infrastructure exists to ensure older people have adequate dietary intake.

Resistance Training Restores Muscle Sensitivity To Feeding

An interesting paper on exercise, feeding, and muscle; abstract:

Normally, skeletal muscle mass is unchanged, beyond periods of growth, but it begins to decline in the fourth or fifth decade of life. The mass of skeletal muscle is maintained by ingestion of protein-containing meals. With feeding, muscle protein synthesis (MPS) is stimulated and a small suppression of muscle protein breakdown (MPB) occurs, such that protein balance becomes positive (MPS>MPB). As the postprandial period subsides and a transition toward fasting occurs, the balance of muscle protein turnover becomes negative again (MPB>MPS). Thus, during maintenance of skeletal muscle mass, the long-term net result is that MPS is balanced by MPB. Acutely, however, it is of interest to determine what regulates feeding-induced increases in MPS, since it appears that, in a number of scenarios (for example aging, disuse, and wasting diseases), a suppression of MPS in response to feeding is a common finding. In fact, recent findings point to the fact that loss of skeletal muscle mass with disuse and aging is due not chronic changes in MPS or MPB, but to a blunted feeding-induced rise in MPS. Resistance exercise is a potent stimulator of MPS and appears to synergistically enhance the gains stimulated by feeding. As such, resistance exercise is an important countermeasure to disuse atrophy and to age-related declines in skeletal muscle mass. What is less well understood is how the intensity and volume of the resistance exercise stimulus is sufficient to result in rises in MPS. Recent advances in this area are discussed here, with a focus on human in vivo data.

To summarize: feeding, particularly of protein, favors muscle buildup as opposed t breakdown and fasting does the opposite.  Muscle loss with age seems linked to suppressed muscle buildup from feeding and this suppression can be reduced by resistance training.  Therefore, resistance training helps to reduce/prevent age-related muscle loss, possibly through enhancing feeding-related stimulation of muscle protein synthesis.  Hence the importance of resistance training and (protein) feeding (albeit of course not in excess).

Coffee And Cancer Risk

Here is a paper on coffee consumption and cancer risk from several years ago,  Bottom like is that there doesn't seem to be a big effect either way; coffee can cause decreased risk for some cancers, but possibly increased risk for childhood leukemia with maternal coffee drinking during pregnancy. The data are "limited and inconsistent" in some cases; overall it seems like a "wash" based on these findings, no big effect. Abstract:

We reviewed available evidence on coffee drinking and the risk of all cancers and selected cancers updated to May 2016. Coffee consumption is not associated with overall cancer risk. A meta-analysis reported a pooled relative risk (RR) for an increment of 1 cup of coffee/day of 1.00 [95% confidence interval (CI): 0.99-1.01] for all cancers. Coffee drinking is associated with a reduced risk of liver cancer. A meta-analysis of cohort studies found an RR for an increment of consumption of 1 cup/day of 0.85 (95% CI: 0.81-0.90) for liver cancer and a favorable effect on liver enzymes and cirrhosis. Another meta-analysis showed an inverse relation for endometrial cancer risk, with an RR of 0.92 (95% CI: 0.88-0.96) for an increment of 1 cup/day. A possible decreased risk was found in some studies for oral/pharyngeal cancer and for advanced prostate cancer. Although data are mixed, overall, there seems to be some favorable effect of coffee drinking on colorectal cancer in case-control studies, in the absence of a consistent relation in cohort studies. For bladder cancer, the results are not consistent; however, any possible direct association is not dose and duration related, and might depend on a residual confounding effect of smoking. A few studies suggest an increased risk of childhood leukemia after maternal coffee drinking during pregnancy, but data are limited and inconsistent. Although the results of studies are mixed, the overall evidence suggests no association of coffee intake with cancers of the stomach, pancreas, lung, breast, ovary, and prostate overall. Data are limited, with RR close to unity for other neoplasms, including those of the esophagus, small intestine, gallbladder and biliary tract, skin, kidney, brain, thyroid, as well as for soft tissue sarcoma and lymphohematopoietic cancer.

I don't drink coffee myself, but based on these data overall it seems not do any harm taking all risks together - although pregnant women may want to ask their doctor about the risk in that specific case.

Dietary Lapses

What is the frequency and predictors of dietary lapses?  A paper from several years ago looks into this, abstract:

BACKGROUND:

Adherence to dietary prescriptions is critical for successful weight loss and weight loss maintenance. However, research on specific instances of inadherence (lapses) is limited, and findings regarding the frequency, nature, and causes of lapses are mixed. Additionally, no studies have examined lapses over the course of a weight loss program.

PURPOSE:

In the context of a reduced calorie diet prescribed as part of a behavioral treatment, we aimed to characterize lapse occurrence, examine lapse frequency across treatment, examine predictors of lapses, and assess the relationship between lapses and weight loss.

METHODS:

Adults (n = 189) enrolled in a 12-month behavioral weight loss program completed ecological momentary assessment (EMA) at baseline, mid-treatment, and end of treatment. At each EMA survey, participants indicated whether a lapse had occurred, and responded to questions assessing situational, environmental, and affective states.

RESULTS:

Lapse frequency showed a curvilinear relationship over time, such that frequency first decreased and then increased. Lapse frequency at baseline was negatively associated with early and overall weight loss. Lapses most often occurred at home, in the evenings, on the weekends, and entailed eating a forbidden food. Greater overall levels of assessed affective and environmental triggers predicted lapses, and greater momentary hunger and deprivation, and the presence of palatable food, also prospectively predicted lapses.

CONCLUSIONS:

In addition to characterizing lapse frequency, the current study identified prospective predictors of lapses across treatment. These findings support the importance of lapses to weight control and provide insight for potential targets of intervention to prevent lapse occurrence.

One point I would raise in response to: "Lapses most often occurred at home, in the evenings, on the weekends, and entailed eating a forbidden food. Greater overall levels of assessed affective and environmental triggers predicted lapses, and greater momentary hunger and deprivation, and the presence of palatable food, also prospectively predicted lapses" is to suggest that a pre-planned cheat meal (for those more overweight) or cheat day (or those who cab be more flexible, who have less weight to lose) may alleviate some of these problems.  The key is discipline, not to "cheat" all week.  "Cheating" may help reset metabolism and leptin levels and avoid the slowing of metabolism that accompanies dieting (although this requires more evidence).  The psychological benefits are obvious.

Resistance Training And Muscle Metabolism

Here is a paper from several years ago formally demonstrating what bodybuilders have long put into practice: resistance training affects protein turnover in skeletal muscle so as to result in muscle growth.  Abstract:

PURPOSE:

Acute bouts of resistance exercise and subsequent training alters protein turnover in skeletal muscle. The mechanisms responsible for the changes in basal post-absorptive protein turnover and its impact on muscle hypertrophy following resistance exercise training are unknown. Our goal was to determine whether post-absorptive muscle protein turnover following 12 weeks of resistance exercise training (RET) plays a role in muscle hypertrophy. In addition, we were interested in determining potential molecular mechanisms responsible for altering post-training muscle protein turnover.

METHODS:

Healthy young men (n = 31) participated in supervised whole body progressive RET at 60-80% 1 repetition maximum (1-RM), 3 days/week for 3 months. Pre- and post-training vastus lateralis muscle biopsies and blood samples taken during an infusion of 13C6 and 15N phenylalanine and were used to assess skeletal muscle protein turnover in the post-absorptive state. Lean body mass (LBM), muscle strength (determined by dynamometry), vastus lateralis muscle thickness (MT), myofiber type-specific cross-sectional area (CSA), and mRNA were assessed pre- and post-RET.

RESULTS:

RET increased strength (12-40%), LBM (~5%), MT (~15%) and myofiber CSA (~20%) (p < 0.05). Muscle protein synthesis (MPS) increased 24% while muscle protein breakdown (MPB) decreased 21%, respectively. These changes in protein turnover resulted in an improved net muscle protein balance in the basal state following RET. Further, the change in basal MPS is positively associated (r = 0.555, p = 0.003) with the change in muscle thickness.

CONCLUSION:

Post-absorptive muscle protein turnover is associated with muscle hypertrophy during resistance exercise training.

It is always comforting when science supports popular conception.