Recognizing the connection between neurodegenerative diseases and aging: research, risks, and new treatments. The rate at which the world’s population is aging is unprecedented. One billion people are 60 years of age or older today, and by 2050, that number is predicted to double. One of the main causes of neurodegenerative diseases (NDDs) and their related conditions, such as vascular disease, is aging.

After the ages of 60 to 65, there is a significant increase in the risk of developing NDDs, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). The prevalence of AD increases from 5% among those 65 to 74 to 13% in the next ten years and 33% after the age of 85. Dementia affects 55 million people today, and by 2030, that figure is expected to rise to 78 million. The second most common cause of disability-adjusted life years (DALYs), which include years of life lost (YLLs) and years lived with disability (YLDs), is dementia. Between 60 and 80 percent of these cases are caused by AD.

In addition to the psychological and physical strain of caring for people with NDDs, there will likely be a significant increase in the financial burden. Between 2015 and 2050, the cost of dementia care alone is expected to tenfold increase, reaching $91 trillion. Since there is currently no cure for NDDs, research is being done to create treatments that can improve physical and cognitive function or at the very least slow the disease’s progression.

Aging and Neurodegenerative Diseases
Using a complex adaptive system (CAS) model often referred to as a “network of networks” a recent study published in Signal Transduction and Targeted Therapy investigates the role of aging in NDDs. According to this model, the brain serves as the center of a networked system, and aging-related disruptions cause homeostasis to deteriorate and NDDs to ineffective DNA repair, accumulated genetic mutations, protein accumulation, compromised nutrient sensing, oxidative stress, epigenetic modifications, chronic inflammation (inflammation), stem cell exhaustion, and mitochondrial dysfunction are some of the biological changes brought on by aging that lead to NDDs.

Other aging-related factors in the brain include aberrant neural circuit activity and excessive activation of immune cells (glia). Amyloid-beta (Aβ), hyperphosphorylated tau, and α-synuclein (α-syn) are among the harmful proteins that build up as a result of neuronal mutations and epigenetic modifications.

These proteins worsen mitochondrial dysfunction, increase oxidative stress, and cause neuroinflammation, all of which further harm neurons. These harmful proteins are difficult for senescent glial cells to eliminate, which leads to persistent inflammation. A cycle of inflammation and neuronal damage is produced when dangerous substances enter the brain due to a compromised blood-brain barrier (BBB).

Neurons deteriorate structurally and functionally as their vulnerability increases. Neural connectivity is hampered by a decrease in neurotransmitter levels, a shrinkage in gray matter volume (especially in areas linked to executive functions), and porous white matter. Dopaminergic neuron depletion impairs cognitive, motor, and sensory processing abilities, further deteriorating brain health.

Advances in Aging Research
Numerous facets of neuronal aging have been discovered by research over the past 70 years, including the buildup of mutations, oxidative stress, immune system deterioration, and the part endogenous retroviruses (ERVs) play in tissue aging. Clinical trials examining metformin’s potential to delay aging have been prompted by genetic studies that have identified mutations like AGE-1 and Daf-2 in Caenorhabditis elegans that significantly extend lifespan.

Longer lifespans have been associated with proteins such as sirtuin 1 (SIRT1) and sirtuin 4 (SIRT4), and yeast longevity has been shown to increase by 70% when SIRTs are activated by small molecules. Rapamycin, which blocks the mTOR pathway, has also demonstrated potential for increasing mammalian longevity through lowering protein accumulation and encouraging autophagy.

Fecal microbiota transplants (FMT), senescent cell removal, and young plasma infusion are other experimental anti-aging methods that have been demonstrated to enhance cognitive function in patients with mild cognitive impairment (MCI) and Parkinson’s disease (PD). Additionally, biological aging—a more accurate measure of physiological aging than chronological age can now be assessed thanks to DNA methylation-based aging clocks.

Integrated Anti-Aging Strategies for NDD Prevention
The intricate relationship between aging and NDDs necessitates a multifaceted strategy. Because the brain is closely related to other bodily systems, therapies that focus on immune, hepatic, and cardiovascular health may reduce the risk of NDD. Maintaining gut health helps avoid toxic protein accumulation and systemic inflammation while improving cardiovascular function enhances the delivery of oxygen and nutrients to the brain.

Recent studies emphasize how viral infections, like SARS-CoV-2, can hasten aging and raise an older adult’s risk of developing NDD. Preventive measures that strengthen the immune system and lessen chronic inflammation are therefore essential. Promising Anti-Aging Therapies: Some possible interventions have been investigated to prevent or slow down NDDs.

Blood-Derived Anti-Aging Molecules: These substances enhance motor function, preserve dopaminergic neurons, detoxify toxic proteins, and encourage neurogenesis. Pharmacological Strategies: Preclinical studies have demonstrated the potential of medications such as metformin, GLP-1 receptor agonists, and senolytics, which eliminate senescent cells.

Biological Therapies: Methods like stem cell transplants, gut microbiome rejuvenation through FMT, and young plasma infusions may help halt age-related decline. Targeted Pathway Modulation: By decreasing undesirable protein accumulation and enhancing cellular resilience, rapamycin-induced mTOR pathway inhibition or SIRT protein activation may shield neurons.

Immunotherapies: In addition to established anti-aging measures, antibody-based therapies that target misfolded proteins are being researched. Even though the results of some trials have been inconsistent, research is still being done to improve these tactics and increase their efficacy. Before these strategies are used in clinical settings, larger, longer-term studies are required to validate them.

Neurodegenerative diseases result from a general imbalance in the body’s intricate adaptive systems rather than a single molecular or cellular malfunction. This emphasizes the necessity of coordinated interventions that target several aging-related mechanisms. An all-encompassing strategy that incorporates cognitive training, a nutritious diet, frequent exercise, and anti-inflammatory techniques can help reduce inflammation, improve respiratory and cardiovascular health, and slow neurodegeneration. To develop a comprehensive approach to preventing, treating, and possibly reversing NDDs, these preventive measures should ideally be paired with disease-specific therapies and the management of coexisting conditions.