bims-agimec Biomed News
on Aging mechanisms
Issue of 2025–01–19
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. Metabolism and metabolomics in senescence, aging, and age-related diseases: a multiscale perspective.
  2. Mikhail 'Misha' Blagosklonny's enduring legacy in geroscience: the hyperfunction theory and the therapeutic potential of rapamycin.
  3. The telomere connection between aging and cancer: The burden of replication stress and dysfunction.
  4. Evolution of Human Susceptibility to Alzheimer's Disease: A Review of Hypotheses and Comparative Evidence.
  5. From molecular to physical function: The aging trajectory.
  6. Addressing Healthy Aging: Time to Stop a Tsunami of Rising Alzheimer's Disease.
  7. The systemic evolutionary theory of the origin of cancer (SETOC): an update.
  1. Front Med. 2025 Jan 17.
    Metabolism and metabolomics in senescence, aging, and age-related diseases: a multiscale perspective.
    Ziyi Wang, Hongying Zhu, Wei Xiong.
      The pursuit of healthy aging has long rendered aging and senescence captivating. Age-related ailments, such as cardiovascular diseases, diabetes, and neurodegenerative disorders, pose significant threats to individuals. Recent studies have shed light on the intricate mechanisms encompassing genetics, epigenetics, transcriptomics, and metabolomics in the processes of senescence and aging, as well as the establishment of age-related pathologies. Amidst these underlying mechanisms governing aging and related pathology metabolism assumes a pivotal role that holds promise for intervention and therapeutics. The advancements in metabolomics techniques and analysis methods have significantly propelled the study of senescence and aging, particularly with the aid of multiscale metabolomics which has facilitated the discovery of metabolic markers and therapeutic potentials. This review provides an overview of senescence and aging, emphasizing the crucial role metabolism plays in the aging process as well as age-related diseases.
    Keywords:  age-related diseases; aging; metabolism; metabolomics; senescence
    DOI:  https://doi.org/10.1007/s11684-024-1116-0
  2. Aging (Albany NY). 2025 Jan 12. null
    Mikhail 'Misha' Blagosklonny's enduring legacy in geroscience: the hyperfunction theory and the therapeutic potential of rapamycin.
    David A Barzilai.
      The untimely passing of Dr. Mikhail "Misha" Blagosklonny has left a lasting void in geroscience and oncology. This review examines his profound contributions, focusing on his pioneering the Hyperfunction Theory and his advocacy for rapamycin, an mTOR inhibitor, as a therapeutic agent for lifespan extension. Contrary to traditional damage-centric models, the Hyperfunction Theory rejects damage accumulation as the primary driver of aging. Instead, it redefines aging as a quasi-programmed process driven by the persistent, excessive activity of growth-promoting pathways beyond their developmental roles, leading to age-related pathologies. We explore how Blagosklonny's insights predict rapamycin's ability to decelerate aging by modulating excessive mTOR signaling, supported by empirical evidence across multiple physiological systems, including immune, cardiovascular, cognitive, and oncologic health. His forward-thinking approach, advocating for the cautious clinical use of rapamycin and suggesting personalized, preventive, and combination therapy strategies, has catalyzed interest in translational geroscience. This review synthesizes Blagosklonny's legacy, presenting rapamycin as a foundational pharmacological intervention with potential in managing age-related decline and extending healthspan, and underlines his impact in shifting aging research from theoretical frameworks to actionable interventions. Blagosklonny's work remains an enduring inspiration, paving the way toward treating aging as a modifiable condition.
    Keywords:  geroscience; healthspan; hyperfunction; longevity medicine; rapamycin
    DOI:  https://doi.org/10.18632/aging.206189
  3. Mech Ageing Dev. 2025 Jan 11. pii: S0047-6374(25)00002-8. [Epub ahead of print]223 112026
    The telomere connection between aging and cancer: The burden of replication stress and dysfunction.
    Virginia Boccardi, Luigi Marano.
      Aging is a complex process that affects individuals at the molecular, cellular, tissue, and systemic levels, arising from the cumulative effects of damage and reduced repair mechanisms. This process leads to the onset of age-related diseases, including cancer, which exhibits increased incidence with age. Telomeres, the protective caps at chromosome ends, play a crucial role in genome stability and are closely connected with aging and age-related disorders. Both excessively short and long telomere lengths may contribute to cancer development when their balance is disrupted. Fragile telomeres, characterized by abnormalities and replication stress, may provide novel insights into the connection between aging and cancer. The accumulation of fragile telomeres, possibly due to intense replicative stress, may represent a key factor. Given the dynamic nature of telomeres, large longitudinal studies are essential for understanding their role in aging and cancer susceptibility, which is crucial for developing effective strategies to promote healthy aging and mitigate cancer risk.
    Keywords:  Aging; Cancer; Telomeres
    DOI:  https://doi.org/10.1016/j.mad.2025.112026
  4. Evol Anthropol. 2025 Mar;34(1): e22054
    Evolution of Human Susceptibility to Alzheimer's Disease: A Review of Hypotheses and Comparative Evidence.
    Isabel August, Pascal Gagneux, Katerina Semendeferi, Maria Carolina Marchetto.
      Primates rely on memory to navigate both physical and social environments and in humans, loss of memory function leads to devastating consequences. Alzheimer's disease (AD) is a neurodegenerative disease which begins by impacting memory functioning and is ultimately fatal. AD is common across human populations and its prevalence is predicted to rise with increases in the aging population. Despite this, the full AD phenotype has not been observed in any other nonhuman primate species. While a significant amount of research has been devoted to understanding the immediate mechanisms involved in AD pathogenesis in humans, less research has focused on why humans are particularly vulnerable to neurodegenerative diseases like AD. Here we explore hypotheses on the evolution of distinct human susceptibility to AD and place these in the context of findings from comparative neuroanatomical and molecular studies and discuss recent evidence for evolutionary changes protective against AD in the primate lineage.
    Keywords:  Alzheimer's disease; aging; comaprative anatomy; evolution; neurodegenerative disease; primates
    DOI:  https://doi.org/10.1002/evan.22054
  5. Curr Res Physiol. 2025 ;8 100138
    From molecular to physical function: The aging trajectory.
    Tom A H Janssen, Caroline V Lowisz, Stuart Phillips.
      Aging is accompanied by a decline in muscle mass, strength, and physical function, a condition known as sarcopenia. Muscle disuse attributed to decreased physical activity, hospitalization, or illness (e.g. sarcopenia) results in a rapid decline in muscle mass in aging individuals and effectively accelerates sarcopenia. Consuming protein at levels above (at least 50-100% higher) the current recommended intakes of ∼0.8 g protein/kg bodyweight/d, along with participating in both resistance and aerobic exercise, will aid in the preservation of muscle mass. Physiological muscle adaptations often accompany the observable changes in physical independence an older adult undergoes. Muscle fibre adaptations include a reduction in type 2 fibre size and number, a loss of motor units, reduced sensitivity to calcium, reduced elasticity, and weak cross-bridges. Mitochondrial function and structure are impaired in relation to aging and are worsened with inactivity and disease states but could be overcome by engaging in exercise. Intramuscular connective tissue adaptations with age are evident in animal models; however, the adaptations in collagenous tissue within human aging are less clear. We know that the satellite muscle cell pool decreases with age, and there is a reduced capacity for muscle repair/regeneration. Finally, a pro-inflammatory state associated with age has detrimental impacts on the muscle. The purpose of this review is to highlight the physiological adaptations driving muscle aging and their potential mitigation with exercise/physical activity and nutrition.
    Keywords:  Atrophy; Exercise; Inflammaging; Nutrition; Protein; Sarcopenia; Skeletal muscle physiology
    DOI:  https://doi.org/10.1016/j.crphys.2024.100138
  6. Aging Dis. 2025 Jan 08.
    Addressing Healthy Aging: Time to Stop a Tsunami of Rising Alzheimer's Disease.
    Nobel Chenggong Zong, Yuhan Zhang, Yuanli Huang, Hua Cai.
      Alzheimer's disease [AD] disproportionately affects our seniors, diminishing their health and life expectancy. As the world population grows older, the collective burden of AD has become unsustainable. Globally, there were 43.8 million patients in 2016, with a projection of affecting 152 million by 2050. Recent discoveries have shown that molecular changes characteristic to AD manifested 20 years before discernable neurological phenotypes emerge. It is feasible to halt or reverse this pathological process before reaching an irremediable stage. To take advantage of this treatment window, we need to make rapid progress in early detection and monitoring, targeted implementation of preventative measures, invention of novel therapeutics, and pragmatic ramping-up of relevant supporting policies. PET is a powerful tool for prognosis. The utilization of AI technology, on the other hand, has favorable features of low cost per capita, easy dissemination and broad scale data collection to uncover previously unknown hotspots or risk factors. FDA approved drugs, lecanemab and donanemab, have started to show efficacy to put a pause on AD progression. Additional clinical data will enable comprehensive evaluation of the impacts of these drugs. Gene therapy holds the potential of eliciting long term protection, while several candidate loci have been identified. The urgency of a tsunami of rising AD epidemiology demands rapid actions on all fronts of advanced diagnostics, monitoring, preventative and interventive strategies.
    DOI:  https://doi.org/10.14336/AD.2024.1476
  7. Mol Med. 2025 Jan 14. 31(1): 12
    The systemic evolutionary theory of the origin of cancer (SETOC): an update.
    Antonio Mazzocca, Giovanni Ferraro, Giovanni Misciagna.
      The Systemic Evolutionary Theory of the Origin of Cancer (SETOC) is a recently proposed theory founded on two primary principles: the cooperative and endosymbiotic process of cell evolution as described by Lynn Margulis, and the integration of complex systems operating in eukaryotic cells, which is a core concept in systems biology. The SETOC proposes that malignant transformation occurs when cells undergo a continuous adaptation process in response to long-term injuries, leading to tissue remodeling, chronic inflammation, fibrosis, and ultimately cancer. This process involves a maladaptive response, wherein the 'endosymbiotic contract' between the nuclear-cytoplasmic system (derived from the primordial archaeal cell) and the mitochondrial system (derived from the primordial α-proteobacterium) gradually breaks down. This ultimately leads to uncoordinated behaviors and functions in transformed cells. The decoupling of the two cellular subsystems causes transformed cells to acquire phenotypic characteristics analogous to those of unicellular organisms, as well as certain biological features of embryonic development that are normally suppressed. These adaptive changes enable cancer cells to survive in the harsh tumor microenvironment characterized by low oxygen concentrations, inadequate nutrients, increased catabolic waste, and increased acidity. De-endosymbiosis reprograms the sequential metabolic functions of glycolysis, the TCA cycle, and oxidative phosphorylation (OxPhos). This leads to increased lactate fermentation (Warburg effect), respiratory chain dysfunction, and TCA cycle reversal. Here, we present an updated version of the SETOC that incorporates the fundamental principles outlined by this theory and integrates the epistemological approach used to develop it.
    Keywords:  Archaea; Cancer theories; Endosymbiosis; Evolution; Mitochondria; Systems biology; Warburg effect
    DOI:  https://doi.org/10.1186/s10020-025-01069-w
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