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Aging is a big risk factor for long-term illnesses, problems with organs, and a drop in the body's ability to heal itself.
12 hallmarks of aging: Genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are grouped into three categories: primary, antagonistic, and integrative
The interdependence of aging traits means that experimental enhancement or weakening of a particular trait will usually affect other traits as well. Three criteria must apply to any trait of aging: (1) the time-dependent manifestation of changes accompanying the aging process, (2) the possibility of accelerating aging through experimental enhancement of the trait, and- most importantly - (3) the ability to slow, halt or reverse the aging process through therapeutic interventions on the trademark.
Aging is an inevitable multifactorial process. Aging-related changes manifest as the “hallmarks of aging,” cause organ functions to decline, and increase the risk of disease and death. Aging is associated with systemic changes in the concentrations of molecules such as metabolites. However, whether such changes are merely the consequence of aging or whether these molecules are drivers of aging remains largely unexplored. If these were blood-based drivers of aging, then restoring their concentration or functions to “youthful” levels could serve as an anti-aging intervention.
The increasing life expectancy means a potential increase in the morbidity and prevalence of aging-related diseases, including cardiovascular , musculoskeletal , oncological , and neurological diseases , such as Ischemic stroke
In humans, markers or risk factors for Aging / Senescence and age-related disease include IGF-1, insulin, glucose, insulin resistance, HbA1c, C reactive protein (CRP), hypertension, and high cholesterol. These can be affected by dietary composition and by fasting periods
Aging is defined as the time-related diminution and disappearance of the physical activities that all animals and humans on Earth pass through. In recent decades, due to the improvement of living conditions and the increase in living standards in developed and developing countries, the life span of people has significantly increased.
Consequently, the number of people aging is much greater than before, and the percentage of people over 60 will rise to 22% by the end of 2050
One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, Nicotinamide adenine dinucleotide (NAD+) , whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Only a few activators of NAMPT / Nicotinamide phosphoribosyltransferase, which are supposed to increase Nicotinamide adenine dinucleotide (NAD+) , have been developed so far. The NAD + salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway
NaAD, nicotinic acid adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase; NMNAT, nicotinamide/nicotinic acid mononucleotide adenylyltransferase; NRK, nicotinamide riboside kinase; PPi, pyrophosphate; PRPP, 5-phosphoribosyl 1-pyrophosphate. The NAD+ salvage pathway, which is the dominant pathway in most tissues, is indicated by red arrows.
SIRT1 is a protein deacetylase whose activity is dependent on the availability of a coenzyme called nicotinamide adenine dinucleotide, Nicotinamide adenine dinucleotide (NAD+) (; ), suggesting that the availability of NAD+ is indispensable for counteracting the aging process
In human clinical trials, administration of NAD + precursors to the elderly is being used to address systemic age-associated physiological decline. Administration of Nicotinamide adenine dinucleotide (NAD+) precursors, Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement Nicotinamide adenine dinucleotide (NAD+) production through the NAD + salvage pathway has been demonstrated to slow down aging processes in mice
Increasing age is associated with an increase in Low-grade Chronic Inflammation (inflammaging)) that may contribute to the neurodegenerative process in AD
Aging is characterized by dysregulated immune () and metabolic homeostasis (; ) where there is chronic sterile low-grade inflammation or inflammaging () that involves cellular senescence (; ), immunosenescence (; ; ; ), mitochondrial dysfunction (; ), defective autophagy (; Barbosa et al. 2019 Front. Endocrinol. 9: 790) and mitophagy (; ), dysregulation of the ubiquitin-proteasome system (; ), activation of the DNA damage response (; ), meta-inflammation or metaflammation from chronic overnutrition or obesity (; ), and gut microbiota dysbiosis (; ; ; )
Approximately 15% of adults aged 60 and over suffer from mental disorders, such as dementia and depression.
Cellular Nicotinamide adenine dinucleotide (NAD+) abundance is predominantly controlled by nicotinamide phosphoribosyltransferase,NAMPT, whose function is responsive to nutrient availability
Schematic diagram depicting the role of senescent cells in driving the process of aging. Oxi-inflammatory stress contributes to the development of senescent cells, which gradually accumulate and promote Low-grade Chronic Inflammation (inflammaging) resulting in tissue and organ dysfunctions and a pro-tumorigenic environment characteristic of the aging phenotype. Senescence-associated secretory phenotype (SASP) is a complex milieu of pro-inflammatory cytokines and growth factors that can contribute to inflammatory damage in nearby cells.
It Is not Surprising to Contemplate that Elimination of Senescent Cells or Enabling Their Delayed Development Could Be a Potent Way of Targeting Several Age-associated Disorders, Including the Hallmark Diseases of Twenty-first Century, I.e. Cancer and Diabetes. It Seems Plausible that Even during Aging, Healthier Cellular Functions Can Be Maintained by Inhibiting the Development or Selective Removal of Senescent Cells, Which May Result in a Lower Rate of Incidences of Tumorigenesis and Inflammatory Disorders
Immune function declines with advancing age
Social, psychological, lifestyle and nutritional risk factors can all influence the trajectory of age-related health
Age-related morbidities share common features, including low-grade persistent inflammation, phosphate toxicity, diminished Nrf2 activity, a depleted metabolic capability, depressed mitochondrial biogenesis and a low diversity gut microbiome
Shiels et al. 2019 Biochem Soc Trans 47:1165–72
We propose using new biomarkers (DNA methylation, glycomics, metabolomics, and lipidomics) capable of assessing biological versus chronological age in metabolic diseases
Aged Animals Exhibiting a More Anti-inflammatory Microglial Profile on the High Fiber Diet
Human aging is a natural process where organs like the brain, gut, and gut microbiota slowly deteriorate over time.
Immune systems of very old individuals: loss of immune cells, lymphopenia and reduced diversity of variable receptor genes on B cells / B Lymphocytes and T cells, although this reduction in T cell diversity seems less pronounced than previously thought
By inhibiting DNA methylation it is possible to dramatically decrease the occurrence of other cancer types
Concept of ‘oxi-inflamm-aging’ that Highlights the Role of Immune Cells as Chief Sources of Chronic Oxidative and Inflammatory Stress Which Ultimately Contribute to the Accelerated Rate of Aging of Organisms
In contrast, certain forms of leukemia in mice are actually promoted by inhibiting DNA methylation, suggesting that for some tumors, it is demethylation that has a dominant influence
By inhibiting DNA methylation in a mouse model for intestinal tumors, for example, it is possible to dramatically decrease the occurrence of adenomas
see also:
Age
Age-associated diseases
Aging / Senescence & Food / Diets / Nutrients
Aging / Senescence & Genomic instability
Aging / Senescence & Gut microbiota
Aging / Senescence & Immunity
Aging / Senescence, & Macroautophagy / Autophagy
Low-grade Chronic Inflammation (inflammaging)
Mitophagy
Senescent cells / Cellular senescence
Taurine
DNA Methylation