Metabolic Ageing: July 2024 (Vol. 2)
This issue of the newsletter continues our special focus on Metabolic Ageing. We feature a few runners from Bengaluru, the DEXA scan, and muscle changes in ageing and obesity.
As we age, our metabolism undergoes profound changes, affecting how our bodies process energy, regulate blood sugar and maintain cellular health. This issue is focused on metabolic ageing - research, technology and stories from the community.
From the Longevity Community
In this issue, we are delighted to feature a trio of women runners from Bengaluru! With childhoods enriched in sports, these women, like countless others, got busy with life – moving cities, busy careers, family etc. But their common goal of fitness brought them together as running buddies. Together, they run across various scenic locations in Bengaluru like the Kanteerva Stadium, Cubbon Park, Ulsoor Lake, Iblur Lake, HSR and GKVK campus, and are a constant source of motivation for each other. Let’s take a deep dive into their running journeys and personal stories of grit and endurance!
How did it all start? And where has your “running” journey taken you?
Gunja: I started running by chance in 2018. Wanted to gain some fitness and the treadmill looked like the least intimidating equipment in the gym. Took a month to run 1 km non-stop back then and eventually built up on it with self-training. I found my running buddies through a runners group in Bangalore and with time, a few of us stuck together motivating each other in our shared and sometimes independent goals.
I started out as a solo runner and eventually found friends and a small community to run with post moving to Bangalore from Delhi. I participate in not more than 2-3 events per year with one of the events being an international marathon as currently I am on the path to pursuing the six-star finisher medal.
Amrita: From a young age, I was always involved in sports, eagerly participating in Annual Sports Day and joining every sports team in school and college. I dabbled in handball, basketball, volleyball, kho-kho, and hockey. However, when I moved to Bangalore for my job, participating in team sports became more challenging.
That's when a friend of mine mentioned participating in a 10K race. Curious, I looked up similar events in Bangalore and signed up for my first 10K race. And that was it—there was no stopping me after that! I kept finding more races and slowly started building my endurance.
The running community is such a positive environment, and I absolutely love the vibes. You'll find people of all ages pushing themselves to give their best. Every race for me is a competition with myself, and running gives me self-confidence, positivity, and a sense of achievement.
Group runs are a fantastic way to stay consistent, and I usually run with a group on weekends.
I've participated in various races, ranging from 10K to 50K. Within the city, I try not to miss my favorite races, such as the TCS 10K and the Bengaluru Half Marathon. I've also run in different cities, including the New Delhi Full Marathon and the Tata Mumbai Marathon. I have also participated in Berlin Marathon 2023. One of my proudest moments was running the Malnad Ultra 50K.
How did you find your group of runners and how do you help each other as a team of runners?
Amrita: In Bangalore, there are many running groups to choose from. I recommend joining one that's close to your home to ensure consistency. Running with a group helps foremost with consistency and safety, especially since we often start our runs before sunrise. You'll almost always find someone running at your pace, making it easier to hit your targets together.
Joining a running community also provides valuable insights and support. Whether it's tips on hydration, warm-up and cool-down routines, or conversations about injury prevention and recovery, you'll benefit from the collective experience of the group.
Running with friends or a community makes challenging workouts like hill repeats, intervals, or long runs more enjoyable and less daunting. It also helps you stay consistent, as the shared motivation and accountability keep everyone on track. Balancing group runs with busy schedules can be tricky, but the camaraderie and support make it worth the effort.
Gunja: Carving out time first thing in the morning for our personal ambitions is the best way to beat before the schedule gets to you.
Any nutritional or other health hacks that support your endurance?
Gunja: Big believer in Unived’s vegan protein and keeping the mind and body happy with a balanced diet. Everything is great in moderation.
Amrita: Staying hydrated and eating clean are my go-to strategies. Proper hydration is crucial for maintaining energy levels and overall performance, especially during long runs. I make sure to drink plenty of water throughout the day and use electrolyte solutions during intense training sessions or races.
Eating clean means focusing on whole, unprocessed foods. I aim for a balanced diet that includes a good mix of carbohydrates, proteins, and healthy fats. Carbs fuel my runs, proteins aid in recovery, and healthy fats keep me satiated and provide sustained energy. And, of course, getting enough rest and sleep is just as important to allow the body to recover and perform at its best.
Latika Roy, another super-fit member of this trio, doesn’t let her age get in the way of her fitness ambitions! Read on as she lets us in on her story and strategy to stay youthful and fit in the face of increasing chronological age.
How did you choose to start running?
Latika: Since childhood, I was always into sport and played Basketball till the National level. However, post-marriage, children, and corporate life, it all went in the background. With children moving to college, I realised I had time at hand that I could put to things of my interest. Running seemed the most doable activity that I could pick at my pace and time and go solo. Bangalore's weather and running culture made the decision easy.
How do you specifically manage your training and recovery so that you prevent injuries and stay resilient?
Latika: Being a sports person I was always conscious about training, rest, recovery, and nutrition playing a holistic role. This got further compounded as I could see runners, especially the young ones, getting injured quite frequently. I try to ensure that I eat clean and do strength training at least twice a week. Swimming is also quite therapeutic in recovery. This has helped me stay on course for the past 10 years or so as a runner.
Any tips for people who want to start with routine physical activity at an older age?
Latika: Running is one of the best exercises and sports that can be picked up at any age. I myself started off in my 40s and am still at it.
The journey should be slow and steady with a like-minded group of people who will motivate and encourage you. Focus on strength training, which is super important. Focus on nutrition, especially protein, as Indian foods can get very carb-dense if not managed well. And the most important of all, getting a routine blood test to ensure basic parameters are green.
Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in ageing and obesity
Muscle degeneration in skeletal muscles is significant in ageing and obesity. Skeletal muscles consist of fast/glycolytic and slow/oxidative fibers. The calf muscle, soleus (SOL), mainly contains slow/oxidative fibers (type I and IIA), while the front leg muscle, extensor digitorum longus (EDL), primarily has fast/glycolytic fibers (type IIB). These fibers differ in distribution, metabolism, and function. Most muscles have a mix of both fiber types, but how these fiber types change under ageing and obesity conditions remains unclear.
This study by Cheng-Le Zhuang and his team at Shanghai Tenth People’s Hospital, published in Cell Death and Disease in June 2024, investigates trends in muscle fibers in ageing and obesity, as well as transcriptional differences between muscle types. The team used muscles from aged and obese mice models and compared them to the control wild-type mice.
Major findings from the study are:
1. Muscle trends:
Degeneration and fiber proportion: Aging and obesity both cause significant skeletal muscle degeneration, notably reducing the cross-sectional area of muscle fibers in the tibialis anterior. All three muscle fiber types—type I, IIA, and IIB—show degeneration. The proportion of type I and IIA (oxidative) fibers decreases, while type IIB (glycolytic) fibers increase in both the tibialis anterior and quadriceps (mixed muscle). This shift is associated with a decline in mitochondrial function.
Aging and obesity cause muscle fiber type change: The SOL (oxidative) and EDL (glycolytic) muscles displayed distinct changes in muscle fiber types during aging and obesity. The cross-sectional area of the SOL muscle significantly decreased in obese mice, with no change in aged mice. In the EDL, both aged and obese mice showed a decrease in cross-sectional area.
2. Transcriptional differences:
RNA sequencing data from SOL and EDL in control mice revealed upregulated glycolysis enzyme genes in fast/glycolytic fibers owing to their anaerobic metabolism, while genes encoding key enzymes for aerobic metabolism were more highly expressed in slow/oxidative muscle.
Fast/glycolytic fibers exhibited increased expression of inflammatory and muscle degenerative genes in both obesity and aging, driven by the NF-κB transcription factor. In contrast, slow/oxidative fibers had upregulated antioxidant gene Nqo-1 and downregulated Tfrc in aging, offering protection against oxidative stress.
Slow/oxidative fibers showed upregulated Mettl21c, a gene linked to slow running performance and autophagic vacuole accumulation, whereas this gene was downregulated in fast/glycolytic fibers in both aging and obesity.
Slow/oxidative fibers and fast/glycolytic fibers exhibited differences in calcium-related genes, and inhibition of calcium channels with an inhibitor significantly increased oxidative fiber proportion.
Human relevance:
The study highlights distinct changes in muscle fiber types and their implications for ageing and obesity in humans. Upregulation of protective genes in slow/oxidative muscle fibers, crucial for maintaining muscles like the vastus lateralis during ageing, is noted. Additionally, the study suggests that the presence of intermuscular or intramuscular fat may contribute to the decline in slow/oxidative fibers in obese individuals, potentially replacing them with fast/glycolytic fibers.
DEXA Body Scan: Advanced Imaging for Metabolic Health Assessment
Body composition analysis plays a crucial role in understanding metabolic health and the ageing process. As individuals age, changes in the ratio of fat mass to lean body mass can significantly impact metabolic function, influencing factors such as insulin sensitivity, bone density, and overall metabolic rate. Accurate measurement of these components is essential for assessing metabolic health and guiding interventions aimed at healthy ageing.
Dual-Energy X-ray Absorptiometry (DEXA) scanning represents a significant advancement in body composition analysis technology. Originally developed for bone density measurements, DEXA has evolved into a comprehensive tool for assessing overall body composition, offering insights into metabolic health parameters.
Key technical features of DEXA body scanning include:
Dual-energy X-ray technology: DEXA utilizes two low-dose X-ray beams with different energy levels to differentiate between various tissue types.
Three-compartment model: DEXA scanning divides the body into three components - bone mineral density, fat mass, and lean soft tissue mass.
Regional analysis: The technology can provide composition data for specific body regions, including the trunk, arms, and legs.
High precision: DEXA offers high accuracy and reproducibility, with typical precision errors of 1-2% for total body measurements.
Low radiation dose: A typical whole-body DEXA scan exposes the patient to approximately 1-10 microsieverts, which is significantly lower than many other medical imaging procedures.
Rapid scanning: Most DEXA scans take between 10-20 minutes to complete, depending on the specific machine and protocol used.
Digital output: DEXA scanners produce detailed digital images and quantitative data, facilitating easy storage and analysis.
The technical capabilities of DEXA are particularly relevant in the context of metabolic health and ageing as DEXA provides precise quantification of fat, lean tissue, and bone mass, enabling accurate tracking of age-related changes in body composition. This detailed analysis supports the assessment of metabolic risk factors and the evaluation of interventions targeting healthy ageing.
From a technical standpoint, DEXA employs sophisticated algorithms to interpret the differential absorption of the two X-ray energies by various tissues. Bone minerals absorb more X-rays than soft tissues, while adipose tissue absorbs less than other soft tissues. By measuring the ratio of absorption of the two energy levels, DEXA software can calculate the proportion of each tissue type.
A sample DEXA report of body fat measurements.
Recent advancements in DEXA technology include:
Improved spatial resolution: Modern DEXA scanners offer pixel sizes as small as 2 mm, allowing for more detailed regional analysis.
Advanced body composition models: Some DEXA systems now incorporate four-compartment models, separately quantifying water content in addition to the standard three components.
Visceral fat quantification: Newer algorithms can estimate visceral adipose tissue volume, a key indicator of metabolic health.
Integration with other health metrics: Some DEXA systems now incorporate additional measurements such as body shape indices and fatty liver indicators.
Machine learning applications: Artificial intelligence techniques are being explored to enhance image processing and data interpretation in DEXA analysis.
The applications of DEXA in metabolic health research and clinical practice are extensive:
Sarcopenia assessment: DEXA can accurately quantify muscle mass, aiding in the diagnosis and monitoring of age-related muscle loss.
Obesity characterization: By providing detailed fat distribution data, DEXA helps in assessing the metabolic risk associated with different fat deposition patterns.
Bone health monitoring: The technology's primary application in bone density measurement remains crucial for osteoporosis risk assessment in ageing populations.
Metabolic syndrome evaluation: DEXA's ability to measure both adiposity and lean mass distribution contributes to comprehensive metabolic syndrome risk assessment.
Intervention efficacy: The precision of DEXA makes it valuable for tracking changes in body composition in response to dietary, exercise, or pharmacological interventions.
DEXA's evolution from a bone density measurement tool to a comprehensive body composition analyzer highlights its pivotal role in metabolic health assessment. By providing detailed insights into fat distribution, muscle mass, and bone density, DEXA offers a nuanced view of the body's metabolic landscape. This precision proves invaluable in both clinical practice and research, particularly in studying ageing populations where subtle compositional changes can significantly impact metabolic function. As DEXA technology continues to advance, incorporating machine learning and more sophisticated algorithms, its potential to uncover new biomarkers and track individual metabolic trajectories grows. However, the true value of DEXA lies not just in its technological capabilities, but in how its data is interpreted and applied within the broader context of an individual's health profile, making it a powerful tool in the ongoing quest to understand and optimize metabolic health across the lifespan.
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