Stay Young, Live Well: How to Delay Aging and Improve Healthspan

“Age is just a number.”

However, aging comes with the baggage of changes in appearance, a prominent decline in most physiological processes, and an increased vulnerability to diseases. It is a degenerative process of our body on a physiological and pathological level. Aging can be attributed to at least 15 different hallmarks at cellular levels as per the ongoing research (López-Otín et al. 2023; Tartiere, Freije, and López-Otín 2024).

Functional decline due to aging can be attributed to several underlying mechanisms such as cellular senescence, telomere shortening, mitochondrial dysfunction, DNA damage and repair decline, and epigenetic changes. 

Targeting the mechanisms of aging is the perfect way to counter the hallmarks of aging. Hence, a proper understanding of how the process of aging occurs provides a platform for research on therapeutic agents to counter aging. Let us understand the mechanisms of aging: (Li et al. 2024).

The mechanisms of aging

• Cellular senescence: It is a permanent termination of cell proliferation in response to stress. The arrest of the normal cell cycle results in impaired tissue regeneration and causes aging (Di Micco et al. 2021).
• Telomere shortening: It is an important mechanism in aging. The integrity of the telomere and telomerase structure is essential for normal functioning. Hence, progressive telomere attrition promotes cell cycle arrest resulting in senescent cells. Telomere shortening and dysfunction thus become catalysts for aging mechanisms. As DNA replicates, telomeres shorten. Once they reach a critical length, they trigger DNA damage response and trigger the release of cell cycle inhibitory markers, thereby causing aging (Li et al. 2024).
• Mitochondrial dysfunction: It has a close relation with aging. Mitochondria are important cellular organelles for energy conversion and signaling. Intracellular and environmental stress may affect their integrity, resulting in a progressive decline in their function that is attributed to aging (Li et al. 2024).
• DNA damage: It is a key factor that leads to most of the above-mentioned mechanisms. Damaged DNA cells are a source of cellular senescence and cell death that ultimately result in loss of organ function, chronic inflammation, and disease. Mechanical stress, UV radiations, and genotoxins can cause DNA damage that consequently causes aging. Moreover, as aging progresses, DNA repair mechanisms further decline (Li et al. 2024).
• Epigenetic changes: DNA damage is the main culprit for epigenetic changes in aging. The epigenetic changes cause impaired gene expression control and result in somatic heterogeneity, thus causing a decline in most functions (Li et al. 2024).

The mechanisms underlying the aging process are potential targets for therapeutic interventions to delay the aging process and promote longevity.

Interestingly, countering the hallmarks of aging has been of prime importance to human beings since ancient times. There have been several proposed strategies that can help us slow down the process of aging, leading to the path of healthy longevity (Tartiere, Freije, and López-Otín 2024).

Let us learn more about the strategies that promise a better and disease-free life span.

Anti-aging strategies for a better life span

To improve longevity, we must target the hallmark of aging. Here are some important strategies and pharmacological interventions:

• Stem cells to your rescue: Stem cell therapy is a promising option to counter stem cell exhaustion. Stem cells are pluripotent and can generate new cells. Injectable stem cells can replace the body’s damaging tissues with healthier tissues, promote skin rejuvenation and repair, and reduce inflammation and oxidative damage to cells. Moreover, they promote the transportation of mitochondria from stem cells to unhealthy cells to preserve mitochondrial health (Tenchov et al. 2024; Jo et al. 2021).
• Get younger blood: Parabiosis is a process that involves the transfusion of blood from younger individuals to older ones (Fukuoka et al. 2021). Although the anti-aging mechanism remains unclear, parabiosis may function by targeting several aging hallmarks. With soluble chemicals transferred from young blood, the process targets stem cell exhaustion, cellular senescence, inflammation resulting in aging (Inflammaging), and altered communication between cells (Tenchov et al. 2024).
• Get rid of the unwanted: Due to aging, your system is unable to throw damaged cells out of the body, which makes them accumulate. Senotherapy using senolytics prevents oxidative damage to the DNA and inhibits this process of cellular senescence. It also counters the process of telomere shortening, dysbiosis, and epigenetic alteration (Balducci, Falandry, and Silvio 2024; Tenchov et al. 2024).
  • 
    Senolytics are small-molecule drugs that selectively remove senescent cells. They also delay or prevent the process of cell senescence which is a significant aging mechanism. A naturally occurring flavonoid called quercetin, and the tyrosine-kinase inhibitor Dasatinib are good senolytics. Other senolytics include fisetin, luteolin, curcumin, navitoclax. Recently a phyto-marine complex comprising a bioactive fraction of Rhodiola complexed with a marine lipoprotein extract from Trachurus sp. has shown to be effective in research studies. Other promising senolytic drugs include acarbose, 17-α-estradiol, and nordihydroguaiaretic acid (NGDA) (Tenchov et al. 2024).
• Boost the autophagy process: Autophagy removes the unwanted cellular remains and thus maintains homeostasis under stressful conditions. With age, however, this process declines and cell components accumulate to cause cancer, nerve impairment, and metabolic disorders. The autophagy enhancers may expedite autophagy which if impaired triggers aging-related diseases such as Parkinsons and Alzheimer’s disease. Maintaining proper autophagy results in extending longevity (Barbosa, Grosso, and Fader 2018).
• Target cellular metabolism: Scientists have identified a cellular metabolic pathway (mTOR) that actively participates in cellular metabolism and nutrient sensing. This pathway is involved in aging pathways such as stem cell exhaustion, nutrient sensing dysregulation, impaired autophagy, and all the other hallmarks of aging. Manipulating metabolism can counter aging-related pathologies.
  • Rapamycin is a natural product extracted from a bacterial species. It has shown potential use in inhibiting the mTOR pathway to increase longevity. It is a powerful activator of the autophagy process (Tenchov et al. 2024). A study in model organisms shows extended lifespan with Rapamycin treatment (Sharp and Strong 2023).
• Physical exercise: Regular physical activity in the elderly improves metabolism and cognitive health, and maintains muscular, cardiac, and respiratory health. On a cellular level, it inhibits telomere shortening and reduces oxidative stress, cellular inflammation, impaired autophagy, genomic instability, and telomere attrition thereby improving longevity (Tenchov et al. 2024).
• Intermittent fasting: It is the most promising dietary intervention that results in calorie intake restrictions resulting in longevity. The possible mechanisms involve the activation of certain enzymes and inhibition of the mTOR pathway. Fasting helps manage proteins, and antioxidant enzyme production that help manage stress and diseases at a cellular level. It is an easy and proven way to counter all the hallmarks of aging (Tenchov et al. 2024). Pharmacological intervention with calorie restriction mimetics such as metformin, rapamycin, and resveratrol has been effective:
  
  • Metformin, originally an antidiabetic drug, provides anti-aging benefits and is also useful in certain age-related diseases such as cancer and cardiovascular diseases.
  • Rapamycin, through mTOR inhibition, activates autophagy which is an important anti-aging strategy.
  • Resveratrol supplements derived from natural sources have anti-aging effects and are also given for their anti-obesity, anti-cancer, and anti-diabetic effects. Resveratrol regulates autophagy, and mitochondrial function and has a profound antioxidant effect making it a great option for antiaging (Zhou et al. 2021).
• Rejuvenate via reprogramming: Cellular reprogramming is a promising rejuvenating strategy to fight aging. In 2012 it earned a scientist a Nobel Prize for developing the Yamanaka factors- a cocktail of ingredients for cell reprogramming. The process involves converting the terminally matured cells into pluripotent stem cells. The process triggers cellular rejuvenation through inhibition of cellular damage, mitochondrial dysfunction, telomere attrition, and so on (Simpson, Olova, and Chandra 2021).
• Telomere reactivation: Using gene therapy and telomere activators, we can delay telomere shortening and associated aging. A plant extract from Astragalus membranaceus shows a promising effect on bone health, skin quality, and other aging signs (Tenchov et al. 2024). A popular supplement, dehydroepiandrosterone (DHEA), has antioxidant properties that may attenuate telomere shortening (Dismukes et al. 2016).
• Hormesis: This refers to exposing cells to low-stress conditions to trigger beneficial responses. Brain cellular models and animal studies have shown beneficial hormetic responses to enhance longevity (Tenchov et al. 2024).
• Fighting dysbiosis: An imbalance in the gut microbe composition can result in several diseases. A healthy microbiota can be maintained with certain probiotics and prebiotics. Maintaining microbiota can counter dysbiosis, a hallmark of aging, and contribute to longevity (Xiao et al. 2024). Several other supplements can promote a healthy life span through the act of balancing gut microbiota:
  • Probiotic supplementation containing mainly Bifidobacterium and Lactobacillus
    species can take care of gut dysbiosis (Tenchov et al. 2024).
  • A prebiotic Bimuno galacto-oligosaccharide has successfully been used in a gut microbiota dysbiosis-related aging trial (NCT01303484) (Tenchov et al. 2024).
  • Nicotinamide Adenine Dinucleotide (NAD+) acts through the enzyme Sirtuins that enhance metabolic efficiency and resist oxidative stress. The latest studies have shown the role of NAD+ in antiaging through its interaction with the gut microbiome. Supplementation with NAD+ precursors has shown protection of heart health, neuroprotection, and boosting of muscle strength (Iqbal and Nakagawa 2024). Apigenin, a well-established antioxidant nutraceutical supplement, helps increase NAD+ levels.
  • Natural supplements like berberine help regulate intestinal flora which helps in the management of many chronic diseases (Zhang et al. 2020).
• 
  Hormone replacement and dietary supplements: Aging decreases hormonal levels and several vital minerals. Hormonal supplements can replenish the hormones and maintain bone and muscular health. Several supplements are being studied and have shown promising effects in countering the aging hallmarks.
  • Mineral and vitamin supplements can help to deal with hair loss and skin aging. Vitamin C and E possess antioxidant properties and are used as anti-aging supplements. Vitamin C is involved in collagen synthesis and protein metabolism (Tenchov et al. 2024).
  • Several antioxidant drugs have also been recommended as anti-aging drugs. They include curcumin, beta-carotene, α-Lipoic acid, L-Glutathione, Co-enzyme Q 10, and fermented Papaya extract (Tenchov et al. 2024).

Correct identification of aging targets, lifestyle modifications, maintenance of gut microflora, and use of appropriate supplements can delay physiological changes that occur due to aging and help improve quality of life. The ongoing research to counter the hallmarks of aging offers a ray of hope for better quality and a greater span of life.

Here at Pristine’s, we care about your health. Therefore, Pristine’s recommends that you consult with your doctor before embarking on any significant alterations in your eating habits, nutritional supplement intake, or exercise routine. Our blogs are not able, nor intended, to substitute for professional, personalized medical advice. We ask that you discuss any points of interest raised in these blogs with a trusted medical professional.

We wish you optimal longevity and health.

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References:

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