We Help People Dealing With Aging By Curating Relevant Information and News About Aging and Anti-Aging.

getting-older-news-logo

Unveiling the Fountain Of Youth

By Tom Seest

Can We Unlock the Secrets Of Anti Aging Genes?

At GettingOlderNews, we help people who want to learn more about aging and anti-aging.

Human cells age faster as DNA damage accumulates over time, speeding the onset of diseases while decreasing lifespans and lengthening lives. Reversing this process through stem cell transplantation could greatly extend lifespans while slowing disease onset.
Researchers have already demonstrated how reprogramming epigenetics can rejuvenate cells. Salk researchers used Yamanaka factors to activate genes in middle-aged mice and reverse some of the effects of aging.

Can We Unlock the Secrets Of Anti Aging Genes?

Can We Unlock the Secrets Of Anti Aging Genes?

What Does Klotho Have to Do with Aging?

Klotho is an anti-aging protein that serves as a regulator of cellular senescence. Studies have revealed it to protect cells from oxidative stress and extend their lives, and studies suggest it could prevent neurodegenerative disorders like Alzheimer’s and Parkinson’s. Studies also reveal its presence in mice expressing it overexpressing it can improve cognitive performance – though whether directly or indirectly through other proteins remains unknown.
Klotho gene, located on chromosome 13, encodes an integral membrane protein with large extracellular and short intracellular domains, capable of being cleaved off during transmembrane transport to form 130kDa soluble form known as Klotho (known as Soluble Klotho). This form serves as the main functional form for blood and cerebrospinal fluid fluid.
Studies have demonstrated that soluble klotho is effective at inhibiting cell senescence by increasing phosphorylation of PI3K/Akt and Erk, and decreasing phosphatase activity of p53. Its effect has been seen across various cell types, including human primary hippocampal neurons as well as pancreatic cells of type 1 diabetic patients.
Klotho has been shown to interact with gangliosides found in the outer leaflet of cholesterol-rich lipid rafts through low-affinity interactions between these gangliosides and its KL domains, in turn mediating interactions that inhibit phosphatidylinositol 3-kinase signalling in HeLa cells and human embryonic kidney cells. Furthermore, Klotho-bound to lipid rafts inhibits this signalling pathway as well.
Recent studies have demonstrated that Klotho is expressed in mesenchymal progenitors, where it promotes osteogenic differentiation while inhibiting osteoclastogenesis and alveolar bone formation and regeneration non-cell autonomously. Klotho’s expression among these progenitors may play an integral part in maintaining human skeletal health and is thus an attractive target therapy to increase homeostasis in aging adults.

What Does Klotho Have to Do with Aging?

What Does Klotho Have to Do with Aging?

What Makes Cisd2 So Vital in the Fight Against Aging?

Cisd2 is a gene that regulates mitochondrial function and cell death control, as well as autophagy initiated by BIK proteins; however, its function in longevity remains unknown. SIRT7 uses it as its substrate; this interacts with several other proteins including p62. Additionally it regulates cellular senescence and DNA repair.
Recent studies have demonstrated that high levels of Cisd2 promote longevity in mice. Unfortunately, its causes for gradual decrease during the natural aging process remain unknown; we and others have demonstrated this decrease can occur via either down-regulating gene expression or through reductions in protein levels.
There has been speculation that microRNAs (miRNAs) could play a part in the age-dependent decrease of CISD2 expression. These short noncoding RNAs bind directly to the 3′ untranslated region (3′-UTR) of an mRNA through base pair complementarity binding, leading to either degradation or translational repression – Cisd2 is potentially targeted by many miRNAs, including miR-449a.
An earlier study demonstrated that CISD2 interacts with GiMAP5, an ER membrane protein present in HEK 293 cells. Utilizing coimmunoprecipitation and other techniques, researchers discovered that both proteins were associated with each other and often cofractionated together within mitochondria-associated ER membranes (MAMs). They further demonstrated how CISD2’s presence increased cytosolic Ca(2+) buffering at mitochondria.
Overexpression of CISD2 in mice was shown to lessen brain mass loss and formation of reactive oxygen species during aging and prevent b-amyloid toxicity and neuronal death in an Alzheimer’s mouse model. Furthermore, this approach restored mitochondrial structure and function in aged hearts. Furthermore, exercise stimulated Cisd2 transcription in skeletal muscle, suggesting its beneficial effects may partially be attributable to activating this gene.
We used an SH-SY5Y microglial cell line to deplete CISD2, and observed a reduction in M1/M2 microglial polarization as well as decreased levels of the molecule. Future research should conduct in-vivo experiments using human or animal tissues in order to confirm these results.

What Makes Cisd2 So Vital in the Fight Against Aging?

What Makes Cisd2 So Vital in the Fight Against Aging?

Can Sirt6 Gene Reverse Aging?

SIRT6 is one of seven mammalian sirtuins that belong to a family of NAD+-dependent protein deacetylases and mono-ADP-ribosyl transferases known as sirtuins, which regulate several cellular pathways such as DNA repair and metabolism, as well as being involved in age-related diseases and longevity research. SIRT6 has become an attractive target for anti-aging therapies due to numerous studies linking its activity with longevity; furthermore, studies have linked it with binding DNA binding, which inhibited its phosphorylation, activating signaling pathways associated with cell growth senescence or both processes associated with age-related functions associated with aging processes – it’s essential that SIRT6 influences its effects upon these functions associated with aging processes for therapeutic interventions to be effective against disease associated with aging processes associated with longevity or cell growth senescence for effective outcomes when dealing with age-related functions associated with aging processes related to aging processes involved.
Recent research identified a rare variant of SIRT6 associated with exceptional longevity among Ashkenazi Jewish centenarians. Known as centSIRT6, it possesses two linked substitutions (H133Y and D63Y) that allow it to bind DNA more tenaciously than wild-type SIRT6, suppress LINE-1 activity, improve DSB repair capabilities and resist oxidative stress better; plus its histone deacetylase activity was weaker but its mono-ADP-ribosylation ability stronger.
These results demonstrate that SIRT6 acts as both a sensor of DNA damage and key regulator of cellular senescence, possibly acting as a mediator in response to fasting, as well as being related to longevity gene activity. Unfortunately, there remains little understanding as to how this gene impacts cell senescence or interacts with other longevity genes.
Although SIRT6 plays an intricate role in controlling aging, there are very few inhibitors currently available to inhibit its activity. Most are small-molecule compounds that mimic the natural action of this enzyme; one such anthocyanin found in black currants and bilberries is Cyanidin; it can improve SIRT6 stability as well as activity by decreasing production of reactive oxygen species (ROS) and nitrogen species formation.
Recent studies on mice that overexpressed SIRT6 gene have demonstrated its anti-aging benefits, including reduced metabolic decline and senescence as well as restored liver NAD+ levels and glycogen synthesis (GNG). This indicates that SIRT6 may play an essential role in energy metabolism as well as longevity; furthermore it may regulate GNG pathway related to aging processes.

Can Sirt6 Gene Reverse Aging?

Can Sirt6 Gene Reverse Aging?

Can unlocking the power of Adh-1 gene reverse aging?

The adh-1 gene acts as both an anti-aging and anti-cancer gene. Its expression is controlled by hormones, which in turn alter the lifespan of cells. Furthermore, ADH-1 interacts with the HSD3A enzyme and the HSD3A pathway, which is known to control cell proliferation and death. Furthermore, ADH-1 acts as an inhibitor of N-cadherin protein overexpression seen in various cancer types; ADH-1 can prevent binding between N-cadherin protein and E-cadherin, which inhibits cancer cell adhesion/signaling, inhibiting tumor growth while simultaneously decreasing tumor blood vessel permeability as well as increasing tumor cell apoptosis.
ADH-1 has been studied for its effects on N-cadherin expression in various melanoma models. ADH-1 successfully reduced N-cadherin levels in tumor xenografts of melanoma and increased their sensitivity to antineoplastic drugs like Melphalan. Furthermore, ADH-1 enhanced Melphalan delivery to tumor vasculature and induced N-cadherin-dependent apoptosis; however, the combination has yet to be tested in Phase I/II clinical trials.
ADH-1 is expressed by both plants and fungi, as well as mammals such as humans. It’s a transcription factor gene which regulates multiple biological processes including cell cycle progression and differentiation as well as signaling pathways such as JAK/STAT signaling cascades as well as mitochondrial oxidative stress regulation and cell migration.
Metabolite profiling was performed using GC-MS to investigate the role of Adh-1 in plant freezing tolerance (Supplementary File 1). Retention time indices and specific mass fragments were used to monitor 263 variables and annotate 78 metabolites; differential accumulation of soluble sugars and amino acids between adh1 mutants and wild-type seedlings under different treatments was noted, especially during cold shock or cold acclimation treatments; during these phases however these levels in adh1 mutants increased more than those present in WT seeds during cold shock/acclimation; after treatment and recovery for 24 h, these changes had reversed themselves completely.
The metabolic network analysis demonstrated a plastic response by adh1 to low-temperature conditions, with more edges connecting in cold shock compared with WT. This indicates that accumulation of metabolites could play a crucial role in shaping plant responses to such low temperatures conditions.

Can unlocking the power of Adh-1 gene reverse aging?

Can unlocking the power of Adh-1 gene reverse aging?

Be sure to read our other related stories at GettingOlderNews to learn more about aging and anti-aging.