Aging is a universal biological process marked by the gradual decline of physiological function across all organ systems. It is driven by a combination of genetic, environmental, and molecular factors that influence the rate of deterioration from birth onward. Although inevitable, scientific progress in regenerative medicine has identified potential ways to mitigate its effects and improve health span.
Among the most promising developments are mesenchymal stem cells (MSCs), which exhibit regenerative, immunomodulatory, and anti-inflammatory properties that may counteract age-related degeneration.
In this review, El Assad et al. examine the role of stem cells in tissue maintenance, disease, and the regulation of aging, emphasizing the importance of understanding their in vivo properties, functions, and mechanisms of control.
The Biology of Aging
Aging reflects the body’s reduced ability to maintain equilibrium, repair damage, and adapt to environmental stressors. It occurs at both the cellular and systemic levels, influencing physical, cognitive, and metabolic functions. Chronological age represents the time elapsed since birth, whereas biological age measures the functional condition of tissues and organs. Biological aging varies significantly among individuals due to differences in molecular processes such as oxidative stress, DNA repair, and cellular metabolism.
Scientists have proposed multiple theories to explain aging. The free radical theory suggests that oxidative molecules accumulate and damage cells over time. The telomere shortening theory focuses on the gradual erosion of chromosome end caps that limit cell replication. The mitochondrial theory highlights the role of declining energy production and increased oxidative stress. Together, these mechanisms lead to progressive cellular dysfunction, tissue deterioration, and loss of resilience.
Recent research emphasizes the goal of extending health span—the period of life spent in good health—rather than lifespan alone. The field of geroscience seeks to identify biological targets that influence aging, aiming to prevent or delay chronic diseases and maintain functional independence in later life.
Systemic Changes Associated with Aging
Aging affects multiple systems simultaneously. In the visual system, reduced contrast sensitivity, slower dark adaptation, and diminished processing speed are common. Hearing loss, known as presbycusis, arises from oxidative damage and cellular loss in the cochlea, reducing the ability to perceive high frequencies and distinguish speech in noisy environments.
Musculoskeletal aging leads to the loss of bone density and muscle strength. Skeletal decline begins after peak bone mass is achieved, and bone loss accelerates in postmenopausal women due to hormonal changes. Muscle atrophy results from both reduced muscle fiber size and loss of fibers, contributing to weakness, frailty, and decreased mobility. Genetic, nutritional, and lifestyle factors influence these processes.
The immune system also undergoes decline, a process termed immune senescence. Aging alters immune cell function and communication, reducing the body’s ability to mount responses to infections or vaccines and increasing susceptibility to cancer, autoimmunity, and chronic inflammation.
Molecular and Cellular Drivers of Aging
In 2013, López-Otín and colleagues identified nine “hallmarks of aging” that form the foundation for understanding age-related decline. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.
More recent discussions have expanded this list to include additional processes such as dysregulated RNA metabolism, altered mechanical properties, microbiome imbalance, chronic inflammation, and defective autophagy. Together, these mechanisms disrupt normal cellular activity, leading to progressive tissue degeneration and functional impairment.
Stem Cells and Tissue Renewal
Stem cells are undifferentiated cells capable of self-renewal and differentiation into various specialized cell types. They serve as a cellular reserve for tissue maintenance, repair, and regeneration. Two primary categories exist: embryonic stem cells, derived from early-stage embryos, and adult stem cells, present throughout the body in specific tissues.
Mesenchymal stem cells (MSCs), a subtype of adult stem cells, have gained attention for their regenerative potential and therapeutic applications. They can be isolated from bone marrow, adipose tissue, umbilical cord, and other sources. MSCs are multipotent, capable of differentiating into bone, cartilage, muscle, and fat cells, and they secrete biologically active molecules that modulate inflammation, enhance repair, and protect against cellular stress.
Mesenchymal Stem Cells in Aging and Regeneration
MSCs play an important role in counteracting age-related physiological decline. They exert effects not only through direct differentiation into functional tissue cells but also through the secretion of paracrine factors, collectively known as the secretome. This includes cytokines, growth factors, and extracellular vesicles such as exosomes.
Exosomes are nanosized vesicles carrying proteins, lipids, and genetic material that facilitate intercellular communication. By transferring molecular cargo to neighboring cells, they can stimulate tissue repair, angiogenesis, and immune modulation. The secretome and exosomes together form a complex signaling network that supports regeneration and reduces inflammation.
Experimental studies have demonstrated the rejuvenating potential of MSCs. In one investigation, transplantation of MSCs from young mice into older mice improved metabolic function, reduced obesity, and enhanced physical activity. Other research indicates that adipose-derived MSCs improve skin elasticity and vascular growth, suggesting applications in aesthetic and wound-healing contexts.
Mechanisms of MSC-Mediated Repair
Mesenchymal stem cells (MSCs) and their secretome influence a wide range of biological pathways that are central to the aging process and tissue repair. They regulate immune responses by releasing anti-inflammatory cytokines that help counteract inflammaging, the chronic, low-grade inflammation associated with tissue damage.
Through their ability to differentiate into osteoblasts, chondrocytes, and other specialized cell types, MSCs replace damaged or aging cells and promote structural repair in musculoskeletal, cardiovascular, hepatic, and neural tissues. They also exhibit anti-fibrotic effects by inhibiting the TGF-β1 signaling pathway and reducing oxidative and hypoxic stress, thereby preventing the buildup of scar tissue that can impair organ function.
Exosomes derived from MSCs carry antioxidant enzymes and signaling molecules that protect cells from oxidative injury and apoptosis, while MSCs further enhance mitochondrial performance to boost cellular energy and resilience. In addition, MSC-derived factors can delay or reverse cellular senescence, preserving the proliferative potential of resident cells, and remodel the extracellular matrix to maintain tissue structure and elasticity.
Growth factors in the MSC secretome stimulate angiogenesis and wound healing by promoting new blood vessel formation, improving oxygen and nutrient delivery to tissues. Finally, MSCs and their exosomes support autophagy—the cellular process that removes and recycles damaged components—helping sustain cellular renewal and contributing to overall longevity.
Therapeutic Implications and Challenges
MSCs exhibit a wide range of regenerative effects, positioning them as a cornerstone of emerging anti-aging and regenerative medicine strategies. They can act directly by differentiating into new tissue or indirectly by releasing bioactive molecules that orchestrate repair processes. These dual functions offer potential applications in managing musculoskeletal degeneration, cardiovascular disease, skin aging, and neurodegeneration.
However, the authors of this review highlight significant challenges that must be addressed before MSC-based therapies can be widely adopted. The therapeutic outcomes of MSC treatment vary depending on donor characteristics, tissue source, and cell culture conditions. Standardized methods for cell preparation, quality control, and delivery must be established to ensure safety and reproducibility. Additionally, while preclinical data are promising, large-scale clinical trials are required to confirm long-term efficacy and assess potential risks such as immune reactions or unintended cell behavior.
Exosome-based therapies may offer a promising alternative by providing the regenerative benefits of MSCs without the complexity of transplanting living cells. Because exosomes can be stored, purified, and standardized more easily than whole cells, they represent a potentially safer and more controllable approach to regenerative treatment.
The Road Forward for Stem Cell–Based Anti-Aging Therapies
Mesenchymal stem cells represent a key frontier in understanding and potentially mitigating the biological mechanisms of aging. Their unique combination of regenerative capacity, immunomodulatory action, and paracrine signaling positions them as valuable tools for maintaining tissue integrity and delaying functional decline. Experimental evidence indicates that MSCs can reduce inflammation, enhance tissue regeneration, and modulate senescence-related pathways, all of which contribute to healthier aging. Continued research is essential to define optimal protocols for MSC isolation, preparation, and administration, as well as to evaluate long-term outcomes in clinical applications.
While stem cell therapy remains an evolving field, the accumulated evidence suggests that MSCs and their secretome could play a central role in future strategies to promote longevity, prevent age-related diseases, and extend the period of health during aging.
Source: El Assaad N, Chebly A, Salame R, Achkar R, Bou Atme N, Akouch K, Rafoul P, Hanna C, Abou Zeid S, Ghosn M, Khalil C. Anti-aging based on stem cell therapy: A scoping review. World J Exp Med. 2024 Sep 20;14(3):97233. doi: 10.5493/wjem.v14.i3.97233. PMID: 39312703; PMCID: PMC11372738.
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