The extension of human life expectancy is associated with significant public health challenges on a global scale, exerting strain on healthcare infrastructures due to the degenerative health conditions prevalent in an aging demographic.
The World Health Organization advocates for the promotion of healthy aging, focusing on
the preservation of functional abilities, postponement of diseases related with aging, and the improvement of autonomy and quality of life for the elderly.
Sarcopenia, a syndrome linked to aging, is characterized by the loss of muscle mass and strength.
The onset of this condition is generally observed between the ages of 30 and 40, with muscle fiber atrophy occurring at a rate of 3-8% per decade, continuing up to the sixth decade of life, thus negatively affecting an individual’s quality of life(1).
Although aging is a primary contributor, the initiation and progression of sarcopenia are also modulated by factors such as lifestyle choices, level of physical activity, dietary patterns, metabolic syndromes, and neuromuscular impairments.
Particularly, a lifestyle characterized by physical inactivity or suboptimal exercise can precipitate what is known as secondary sarcopenia at an early stage(2).
Current therapeutic approaches for sarcopenia essentially involve physiotherapeutic measures aimed at enhancing strength and locomotion proficiency. Advancing our understanding of sarcopenia’s foundational mechanisms can potentially enhance the innovation of targeted therapeutic modalities. Recent scientific inquiry has placed emphasis on the critical roles of mitochondrial impairment and inflammatory processes in its appearance and progression(3).
Mitochondria are linked to a spectrum of pivotal cellular functions within skeletal muscle that are essential for sustaining normal muscular operation and protein homeostasis.
Emerging evidence indicates that mitochondrial dysfunction is a significant factor contributing to the degeneration of skeletal muscle associated with primary aging and is implicated in the exacerbation of secondary aging processes. In contrast, enhancing mitochondrial function has been postulated to mitigate the advent of secondary aging phenomena(4).
Mitochondrial dysfunction is instrumental in the etiology of sarcopenia, as it leads to a decrease in oxidative phosphorylation, an increase in programmed cell death, and compromised calcium ion regulation.
A destructive cycle involving reduced mitochondrial respiratory function, escalated oxidative injury, and faltering mitochondrial quality control mechanisms contributes to the acceleration of skeletal muscle aging. Recent research indicates that mitochondria exhibiting diminished bioenergetic performance serve as a critical indicator that triggers the transition from normal muscular aging to pathogenic muscle aging(5).
In this article, I’ll review the complex interconnection between mitochondrial dysfunction and sarcopenia, alongside the effect of inflammaging on mitochondrial deficits linked to this muscle-wasting condition.
Sarcopenia: loss of muscle and physical function decline
The diminished capability to sustain muscular strength and power increases the susceptibility of older individuals to a heightened incidence of falls, compromised postural stability, and a consequent erosion of independence.
Consequently, the age-associated regression in skeletal muscle function can markedly affect the health and life quality of the geriatric demographic. Therefore, it is imperative to preserve skeletal muscle functionality to ensure continued locomotion, metabolic integrity, and independence within the aging cohort.
Below are key points describing the decrements and consequences related to sarcopenia:
- – Contemporary diagnostic criteria have identified muscular strength as a more reliable indicator of negate e health outcomes compared to muscle mass. The decline in muscular strength that occurs over the later decades may result in an individual at the age of 80 possessing merely 30-50% of the strength typified by a man in his third decade(6).
- – There is a decrease in power and speed of muscle contractions as one ages. The decrease in the ability to rapidly generate force is a significant determinant of functional impairment in the elderly.
- – The necessity for maximal muscular power for activities such as standing from a seated position implies that even minor decrements in mobility can substantially influence the shift from an independent to a dependent state.
- – The decrement of motor units and muscle fibers stands as the principal etiological factor in the development of sarcopenia.
- – Concomitant with generalized muscle atrophy are modifications in the composition of muscle fiber types, with a reduction in the size of both type I and type II fibers in elderly populations when compared to their younger counterparts. Additionally, type II fibers are subject to more pronounced atrophy, indicative of their more rapid degeneration as a function of the aging process.
- – The intrinsic contractile characteristics of muscle tissue are compromised with age. Diminished calcium responsiveness, alterations in actomyosin crossbridge cycling, and impairments in excitation-contraction coupling are fundamental to the observed decrement in muscle contractility associated with aging.
- – Quantitative and qualitative deteriorations in skeletal muscle function engender profound ramifications, including compromised postural stability, an escalated risk of falls, and a decreased capacity to execute routine activities of daily life(2).
Mitochondrial Dysfunction in Muscle Aging
Mitochondria are critical to cellular function, coordinating calcium signaling, the genesis of reactive oxygen species, and the induction of cell death via apoptosis (i.e., programmed cell death) among other pathways.
Figure: Association between mitochondrial dysfunction and sarcopenia in aged muscle(2)
Within skeletal muscle cells, the primary pathway for synthesizing adenosine triphosphate (ATP) – the pivotal molecule for energy transduction in muscle contraction – is mitochondrial oxidative phosphorylation, which is indispensable for the maintenance, proliferation, and proper functioning of skeletal muscle.
Research indicates that the aging process is associated with an exacerbated accumulation of damaged and improperly folded mitochondrial proteins, which in turn disturbs mitochondrial homeostasis. This disturbance leads to an amplification of oxidative stress due to heightened reactive oxygen species production and consequent inflammation
within the skeletal muscle tissue(5).
As we age, there are many connected factors that disturb the balance of proteins in our cells’ mitochondria.
The culmination of these factors compromises the operational efficacy of the mitochondrial (e.g. electron transport chain) and lead to a decrement in ATP synthesis and deterioration in mitochondrial functionality. Such mitochondrial impairments are instrumental in exacerbating muscle atrophy, curtailing muscle protein biosynthesis, augmenting muscle protein catabolism, and they play a contributory role in the onset and advancement of sarcopenia(7).
Consequently, formulating strategies to
preserve mitochondrial protein homeostasis is identified as an essential objective in the fight against sarcopenia and in fostering the longevity of skeletal muscle health.
The interaction between inflammaging and age-related mitochondrial dysfunction.
The aging process is often related to persistent, subdued inflammatory states, termed “inflammaging”. Such a state is contributory to the deterioration of tissue integrity and the emergence of age-correlated pathologies, including
type 2 diabetes mellitus, osteoarthritis, and sarcopenia. Inflammaging exerts deleterious effects on glucose homeostasis, potentiates insulin resistance, and exacerbates oxidative stress, further enhancing the secretion of pro-inflammatory cytokines.
The connection between chronic inflammation with mitochondrial dysfunction is implicated in the pathogenesis of age-related health problems.
This discourse delineates the interrelated mechanisms of inflammation and mitochondrial dysfunction, with a focus on their impact on sarcopenia, cachexia, and other disorders related to aging.
Nitric oxide signaling emerges as a critical intermediary in the interplay between inflammatory processes and mitochondrial functionality within skeletal muscle. When inducible nitric oxide synthase is activated by pro-inflammatory cytokines, it leads to excessive inhibition of the electron transport chain, and upsurge in oxidants, and increased permeability of the mitochondrial outer membrane(8).
In addition, inflammatory processes are known to inhibit mitochondrial biogenesis. This inhibition leads to diminished mitochondrial density as observed in conditions such as cachexia associated with chronic obstructive pulmonary disease. This results in hindered regenerative capacity and further aggravation of mitochondrial dysfunction.
Inflammation perpetuates mitochondrial dysfunction through modulations in nitric oxide signaling, apoptotic induction, and the suppression of mitochondrial biogenesis.
Unraveling these intricate mechanisms will grant a deeper understanding of sarcopenia, cachexia, and other age-related ailments, thereby identifying potential targets for interventions aimed at preserving muscular health during aging.
Figure: Interaction between inflammaging and age-related mitochondrial dysfunction(2)
Summary
Sarcopenia, alongside the concomitant decline in muscular mass attributable to aging, exerts a pronounced influence on the physical capabilities and overall life quality of the geriatric population. Unraveling the fundamental processes responsible for these conditions is crucial for the innovation of effective therapeutic interventions.
Mitochondrial dysfunction has been identified as a contributing factor to muscular debilitation.
Additionally, it is postulated that inflammation may act as an intermediary in the pathogenesis of mitochondrial dysfunction and sarcopenia, with intensified inflammatory responses aggravating these impairments.
The alteration of inflammatory processes may present a viable strategy to alleviate muscle atrophy. Intensive investigation into the inflammatory pathways that correlate with functional decline is imperative to devise interventions that preserve muscular function in the aging population.
One of the most effective ways to ward off sarcopenia as you age is not only by lifting weights frequently and
consuming enough protein to maintain muscle mass, but also by supplementing creatine every day. Creatine monohydrate is the most widely researched supplement on the planet and has wide ranging total body benefits for both men
and women including strength, muscle mass,
brain function and more.
ATP-Fusion is 100% pure creatine monohydrate powder infused with a precise amount of sodium and potassium to deliver more of the performance enhancing benefits you’re looking for. It’s stimulant free which means it can be used any time of day, including pre or post-workout and requires no loading phases or sugar to ensure absorption.
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References:
1. Keller K, Engelhardt M: Strength and muscle mass loss with aging process. Age and strength loss. Muscles Ligaments Tendons J 3:346-50, 2013
2. Xu X, Wen Z: The mediating role of inflammaging between mitochondrial dysfunction and sarcopenia in aging: a review. Am J Clin Exp Immunol 12:109-126, 2023
3. Leduc-Gaudet JP, Hussain SNA, Barreiro E, et al: Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging. Int J Mol Sci 22, 2021
4. Wiley CD, Velarde MC, Lecot P, et al: Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype. Cell Metab 23:303-14, 2016
5. Picca A, Lezza AMS, Leeuwenburgh C, et al: Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets. Int J Mol Sci 18, 2017
6. Daley MJ, Spinks WL: Exercise, mobility and aging. Sports Med 29:1-12, 2000
7. Picca A, Pesce V, Fracasso F, et al: Aging and calorie restriction oppositely affect mitochondrial biogenesis through TFAM binding at both origins of mitochondrial DNA replication in rat liver. PLoS One 8:e74644, 2013
8. Sakellariou GK, Vasilaki A, Palomero J, et al: Studies of mitochondrial and nonmitochondrial sources implicate nicotinamide adenine dinucleotide phosphate oxidase(s) in the increased skeletal muscle superoxide generation that occurs during contractile activity. Antioxid Redox Signal 18:603-21, 2013
