Age-Related Hearing Loss: A Review of a Hot Topic in Audiology

Muhammad Imran Qadir and Munaza Gillani
Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan
Correspondence to: Muhammad Imran Qadir, mrimranqadir@hotmail.com

DOI: https://doi.org/10.70389/PJG.100004

Additional information

• Ethical approval: N/a
• Consent: N/a
• Funding: No industry funding
• Conflicts of interest: N/a
• Author contribution: Muhammad Imran Qadir and Munaza Gillani – Conceptualization, Writing – original draft, review and editing
• Guarantor: Muhammad Imran Qadir
• Provenance and peer-review:
   Unsolicited and externally peer-reviewed
• Data availability statement: N/a

Keywords: Cochlear histopathology, Presbycusis, Mitochondrial dna mutations, Noise-induced hearing loss, Antioxidants.

Peer Review
Received: 3 June 2025
Last revised: 24 July 2025
Accepted: 24 July 2025
Version accepted: 2
Published: 8 August 2025

Plain Language Summary Infographic

Introduction

Hearing is one of the major senses that enables distant communication. Ears are the paired organs that receive and transmit the sound waves coming from air, solids, and liquids. The brain and central nervous system are the structures that manipulate the sound waves. The ear is divided anatomically into three parts, i.e., the external ear, the middle ear, and the inner ear. The vibrations produced by these sound waves strike the tympanic membrane or the eardrum. These vibrations are transmitted to three ossicles (malleus, incus, and stapes). Finally, these sound waves are transferred to the cochlea in the inner ear, causing the basilar membrane to oscillate.

An action potential is generated by the nerve cells present on the basilar membrane. The problem in any part of the ear may lead to hearing impairment. This problem of hearing loss may result from infections, genetic deficit, an increased exposure to noise (intense sound), biochemical insult, tumor growth, head injury and aging. Among different causes of congenital hearing loss, 50% are genetic in nature, 25% are idiopathic, and the remaining 25% are acquired. The genetic causes further comprise syndromic (30%) and nonsyndromic (70%). On the basis of inheritance pattern, 77% of genetic cases are autosomal-recessive, 22% are autosomal-dominant, and 1% are X-linked. While mitochondrial inheritance comprises 1% transfer from the mother. Prelingual deafness poses a real threat to other disabilities. The capability to hear in early growth ages is critical for the normal development of speech and cognition. The hearing impairment also leads to reduced visual reception along with other motor skills of a child.

Causes of Hearing Loss

Viral Infections

Viral infections can lead to up to 40% of hearing loss in humans, which may be congenital or acquired. These viruses may cause mild or severe infections, which may either be unilateral or bilateral. The inner ear structures—hair cells or the organ of Corti—are directly damaged by these viral infections.¹ Cytomegalovirus (CMV, which is a double-stranded DNA virus) is an early acquired virus in utero. More than 1% neonates are infected with this virus in the United States.² A mother infected by this virus in an earlier pregnancy will cause an increase in the number of newborns infected by this virus.^3,4 CMV causes an inflammation in the cochlea, organ of Corti, spiral ganglion, Reissner’s membrane, and scala media.^5,6 The hearing impairment can be diagnosed in infected children at an early age of 27–33 months. Rubella is another virus (RNA single-stranded virus) that also causes hearing loss in infants by maternal infection during early pregnancy. It may manifest as congenital cataract, intellectual disability, microcephaly, cardiac anomalies, and blueberry muffin lesions.⁷

Immunodeficiency virus (HIV) is another single-stranded RNA retrovirus that causes 14%–49% auditory impairment in infected patients.^8,9 Investigations have suggested that HIV causes both central and peripheral infection in the auditory system. HIV has been found associated with vestibular hair cells, tectorial membrane, and the cells of stria vascularis.¹⁰ The severity of this viral infection causes severe hearing impairment in the infected individual.⁹ Hearing loss occurs as a result of acquired viral infections such as measles (a single-stranded RNA virus), which cause 5%–10% hearing loss in the United States.¹¹ Varicella-zoster virus (which is a double-stranded DNA enveloped virus) is transmitted through sneezing and coughing by direct contamination with the fluid from vesicles of an infected person. Another infectious disease that causes hearing loss is mumps (caused by a single-stranded RNA virus), which can also lead to complications such as pancreatitis, oophoritis, infertility, and orchitis.¹² Vaccines and other antiviral drugs can be manipulated to decrease the level of severity of hearing loss in congenital and acquired viral infections.¹³ Use of hearing aids and cochlear implantation is also appropriate.

Noise-Induced Hearing Loss (NIHL)

NIHL is also considered to be a major cause of hearing loss which accounts for 7%–21% of occupational hearing loss in Europe.¹⁴ NIHL refers to the hearing loss in the frequency range from 0.5 to 6 kHz, as an average of both ears or for the better or worse ear.¹⁵ In a study conducted on cement industry workers, it was found that a decrease in hearing ability, which was 5 dB among the younger laborers of age 21–30 years in the 3–6 kHz frequency, and for older laborers, it was 20 dB.¹⁶ Similarly, the study conducted by Leensen suggests that a hearing loss in young and old construction workers was 0–7 dB as compared to the control group.¹⁷ Same results were obtained for NIHL in different studies conducted in the construction industries in different areas. The workers were exposed to noise, resulting in a decrease in hearing ability at a shipyard in India to 6% as compared to the office staff without noise exposure.¹⁸

In three independent studies conducted on over 87,000–140,000 US military personnel, it was reported that a higher-than-expected hearing loss was found among infantry soldiers who had an active experience of war.^19,20 Similar results were obtained on the recruits having a service time of 11.7 months when compared to the nonexposed control.²¹ The farmers who had been using noisy machinery at farms had a higher risk of hearing loss in comparison to nonexposed full-time or part-time farmers.²² In further studies, it was reported that 40% people (mostly young adults) who were using hearing aids for listening to music faced a problem of hearing loss and had been experiencing hearing impairment for 1–20 years.²³ However, hearing loss is also attributed to the genetics of the individual. Many studies have reported that there is a relationship between hearing loss and genetics.^24,25 The genes that are involved in oxidative stress, heat-shock proteins, and endolymphatic potassium transport have been studied.

Other Factors of Hearing Loss

Hearing loss is the inevitable outcome of aging.²⁶ However, there are some older individuals with normal hearing.²⁷ The young individuals are also susceptible to hearing loss. However, the prevalence of hearing impairment in young individuals is lower in comparison to older individuals.²⁸ Among other factors which account for hearing loss are noise exposure,²⁹ cardiovascular diseases,^30,31 exercise,³² and diabetes mellitus (DM).³³ DM has been found to be associated with hearing loss in many studies. The serum glucose directly influences the hearing threshold in diabetic patients.³⁴ The patients suffering from DM have been reported to have a higher incidence of sensorineural hearing loss. The hearing has been found normal during early stages of DM, but 30% of patients with chronic DM had a hearing impairment.³⁵ The most recent studies show that 70% of patients with DM had sensorineural hearing impairment, which suggests that patients with DM type 2 require a higher hearing threshold as compared to healthy controls.³⁶ The loss in sensorineural hearing loss may be caused by hyper viscosity caused either by DM or hypertension. The severity of hearing loss increases with an increase in the glucose level of diabetic patients.

“It was found that there is a delay in interpeak latencies I–III, III–V, I–V in the diabetic groups which suggests delayed transmission of the auditory stimulus in the auditory pathway of the diabetics at the level of brainstem and midbrain.”³⁷ However, there is no supportive evidence available for hypertension to be a cause of hearing impairment.³⁸ Hearing loss has also been reported at a young age. Historical data and recent studies show that the risk of hearing loss is increasing in school and college students.³⁹ Tinnitus is the most prevalent condition among students. In a survey, it was reported that 85% students of American colleges faced the problem of tinnitus.⁴⁰ However, the condition of tinnitus was permanent in 2% students only. Other students had a temporary or rare problem of tinnitus. The problem of tinnitus in Swedish High School students was 9% of 13–19 years of age.⁴¹ At the same time, other reports suggest that the prevalence of tinnitus is 15% in college students.

The students who reported the problem of tinnitus had exposure to loud music (up to 50% students) or workplace noise (29% students).⁴² The problem of tinnitus prevalence increases with an increase in age, especially after mid-50s.⁴³ However, the problem of hearing loss is associated with low socioeconomic conditions of the people. These low socioeconomic conditions are correlated with smoking, insufficient exercise, poor diet, and excessive intake of alcohol.⁴⁴ All of the factors are independently associated with a higher prevalence of hearing loss. The socioeconomic conditions during childhood account for an even greater proportion. However, the process of hearing loss can be delayed and the acuity of hearing loss can be moderated. Changing the environmental and socioeconomic conditions may decrease the prevalence of hearing impairment.

Males are more susceptible to hearing loss than females. However, other studies suggest that there is no correlation between sex and hearing loss. In previous studies, it was reported that non-White ethnicity had a reduced risk of hearing impairment, such as Bangladeshi, Pakistani, and African.⁴⁵ This was associated with melanin, which could have a protective effect on the cochlea against hearing impairment.⁴⁶ However, recent studies have contradictory findings that non-White ethnicity is susceptible to hearing loss. This can be related to poor health conditions in these regions.⁴⁷

Age-Related Hearing Loss (ARHL)

Aging refers to a complicated biological process of gradual and irreversible decline in the physical, physiological, and metabolic abilities of an individual, increasing the risk of vulnerability to diseases and death. Cardiovascular diseases, hypertension, Alzheimer’s disease, type 2 diabetes, arthritis, cataract, osteoporosis, and cancer are all outcomes of the process of aging. Presbycusis or ARHL is also associated with the process of aging, which results from the deterioration of the cochlea, inner hair cells, or other associated structures.

The structural and functional changes in the central nervous system contribute to the process of presbycusis. The hearing loss commences at 30s, increases with the passage of time, and worsens after 70s, hence hearing loss is mild in early ages, gets moderate to severe with increasing age. Even some people do not feel that they have hearing loss unless the situation worsens. The other effects associated with hearing loss include communication difficulties, incident dementia, depression, negative mental state, cognitive decline, social isolation, and falls. It could also be responsible for fatal outcomes in case of roadside incidents. The reasons for ARHL are complex. Genetic background, environment, and lifestyle of an individual contribute to ARHL as shown in Figure 1. ARHL is commonly linked to alterations in the morphology of the inner ear. Other changes associated with ARHL are the those in the nerve pathway, tympanic membrane, and middle ear bones. ARHL is more common in families with severe ARHL. However, the general population is equally affected by the disease.

Genetics of ARHL

The onset of ARHL and its severity are influenced by the inherited variations in multiple genes. Normal functioning of the gene is a prerequisite for the proper functioning of the ear. Any mutation in the described gene will be responsible for the onset of nonsyndromic hearing impairment at an early age. Other genes that are associated with ARHL are also involved in their role in the process of aging and other diseases associated with the process of aging. Alteration in the mitochondrial DNA (mtDNA) is one of the well-studied factors associated with ARHL. Mitochondria are the powerhouse of the cell, which converts the energy obtained from food into a specific form that cells can use. A small amount of DNA is also present in the mitochondria. Mutations occur in mtDNA with aging, including deletions. The damage caused by these mutations results in the buildup of damaging molecules called reactive oxygen species (ROS), the byproduct of energy generation by the mitochondria. The malfunctioning, thus death of the cells, will occur if any damage occurs in mtDNA. Those cells are more susceptible to damage that have high energy requirements. The cells in the inner ear are more affected by this mtDNA damage. This damage will result in the malfunctioning of the cells, thus causing hearing impairment.

The genetic and molecular bases of ARHL can be well studied using mice as an animal model. Different patterns of ARHL are exhibited by different strains and specific loci are associated with increased hearing loss. The onset of hearing loss occurs in 18-month-old CBA/J mice. Other strains, such as C57BL/6, DBA/2G, and BALB/cJ, have an onset of ARHL between 2 and 3 months.46 However, a CBA/J mouse is not susceptible to other diseases and premature hearing impairment.48 The studies report that a loss in hair cells occurs in 18-month-old mice, which causes a high threshold shift, suggesting the loss of hair cells as a factor in hearing impairment.⁴⁹ The degeneration of spiral ganglion takes place as a consequence of hair loss in many animal species, including mice, gerbils, and humans.⁵⁰ The process of aging is strongly correlated with cochlear histopathologies, causing hearing impairment in rhesus monkeys as well as humans.⁵¹ The damage to the hair cells and spiral ganglion ultimately leads to damage to the organ of Corti. The same phenotype is present both in humans and mice during ARHL. The genetic studies of B6 mice show that the locus for hearing loss is present on chromosome 10 and was named “Age-Related Hearing Loss” and represented symbolically as ahl.⁵² The gene which causes the phenotype of hearing loss in mice is called modifier of deaf waddler (mdfw), with the atp2b2 gene mutation, which could be allelic with ahl.⁵³ This ahl locus also contributes to acoustic trauma.⁵⁴ SLC7A8 is another gene that has been found to be linked with ARHL in humans.

In humans, the locus DFNB29 for deafness is present on chromosome 21q22.1 and results from a recessive mutation in CLDN14, which encodes for claudin14, a family of proteins encoded by 27 genes and has the function in stabilizing and maintaining the integrity of basolateral and apical membrane domains, thus preventing the movement of solvents and solutes across the intracellular spaces.⁵⁵ However, the junction is highly specialized and more elaborate between the hair cell and the Dieter cell, so that the ionic barrier is maintained between endolymph and perilymph.⁵⁶ Hearing is a complex trait that demands the interaction and proper functioning of many genes. It is reported that more than 15 quantitative trait loci (QTLs) have been found and mapped, which contribute to the progression of ARHL in laboratory mice.^57,58 However, the recent studies report that hearing impairment caused by the ahl/mdfw locus is associated with cadherin 23 (Cdh23).⁵⁹ In addition to the Cdh23 gene, Gipc3, Cs, and Fscn2 also control the hearing ability. The progression of ARHL is delayed in the +ahl allele in B6 mice; however, the condition is inevitable in these mice. It is suggested that the ahl locus is associated with the damage and loss of the spiral ganglion and the organ of Corti. Another locus called ahl2, present on chromosome 5, may contribute to the retention of hearing.⁵³ The other locus is present on chromosome 11 and represented symbolically as ahl8 in D2 and B6 mice.⁶⁰ The genetic factors presumably control the onset of ARHL, but environmental insult is a major contributor to the damage in the cochlea.

Cellular and Molecular Bases of ARHL

The “longevity genes” and a healthy environment have helped in aging research both in humans and animals.^61,62 The presence of longevity genes and availability of a healthy environment will promote healthy aging and vice versa. The cellular aging model can be categorized into (a) aging as a regulated program and (b) aging as dysregulation. The former category suggests that aging is an adaptation. A limited mitotic division in dividing cells is also an adaptation that causes shortening of the telomere.⁶³ This mechanism ensures cell replacement and also provides defense against cancer. The same condition may be applicable to the aging of the cochlea. The cell death caused by apoptosis, necrosis, or autophagy accelerates the process of aging. The apoptotic pathway, either extrinsic or intrinsic, activates a cascade of reactions that causes cell death by affecting the stability of mitochondrial membranes. The endoplasmic reticulum, on the other hand, under stress stimulus will accumulate Ca2+, activation of caspases and ultimately cause damage in DNA. The death or DNA damage in the cells of the cochlea with the passage of time will cause presbycusis, because the gene expression in the cochlea changes. It will eventually alter the gene expression of important housekeeping genes and membrane lipids.64 In a recent study, it was demonstrated that quantitative analysis of normal ears of 54–89 years of age suggests that cochlear synaptopathy and degeneration of cochlear nerve peripheral⁶⁴ axons may contribute to human presbycusis.

Oxidative stress is another important factor that causes cellular injury. This oxidative attack on cellular DNA, biomolecules, and metabolic pathways will promote environmental stress. According to the free-radical theory of aging, proposed by Herman (1956), “Progressive oxidation is called Aging”. This theory is also applicable to presbycusis. Ototoxicity, noise, and ischemia also exert oxidative stress on the cochlea, leading to cochlear injury (Rybak, Talaska Chap. 8). The modifications in DNA, lipids, and proteins in cochlear cells caused by oxidation will increase during the process of aging. The inactivation or suppression of genes that code for antioxidant enzymes glutathione peroxidase and SOD1 will exacerbate the cochlear pathology in ARHL, including loss of neurons, hair cells, and thinning of stria vascularis. The administration of antioxidants, such as D-methionine, glutathione, and N-acetyl cysteine, causes a reduction in ototoxic and noise injury. The dietary supplementation of vitamin C, vitamin E, and carotenoids will slow the process of degeneration of the cochlea and hearing loss.

The error in mtDNA caused by mutations or ROS will hamper the process of energy production of the cell, thus causing an impairment of the entire cell function (Table 1). The mitochondrial clock theory⁶⁵ is analogous to the free-radical theory of aging. The error in mtDNA in cochlear cells will promote ARHL. The effect can be countered by antioxidants and caloric restrictions. Moreover, cellular aging also contributes to disruption and dysregulation of calcium, promoting neural presbycusis.⁶⁶ The calcium dysregulation also modifies the Cdh23 locus,⁶⁶ thus causing sensory presbycusis.

Table 1: Role of mtDNA & ROS in ARHL.
Factor	Description	Contribution to ARHL
mtDNA	Circular DNA located in mitochondria; encodes proteins essential for oxidative phosphorylation	Mutations/deletions in mtDNA impair energy production in cochlear cells, especially hair cells
mtDNA mutations	Age-related increase in point mutations or deletions	Accumulation leads to mitochondrial dysfunction and cell death in the cochlea
ROS	By-products of mitochondrial respiration; includes superoxide, hydrogen peroxide, etc.	Excess ROS causes oxidative damage to proteins, lipids, and mtDNA in auditory cells
Oxidative stress	Imbalance between ROS production and antioxidant defenses	Leads to mitochondrial damage, apoptosis of cochlear hair cells, and neural degeneration
Antioxidant defenses	Include glutathione, superoxide dismutase, catalase	Age-related decline reduces protection against ROS, exacerbating mitochondrial and cochlear cell damage
Mitochondrial dysfunction	Result of accumulated mtDNA damage and oxidative stress	Impaired adenosine triphosphate production affects high-energy-demanding cochlear cells ® progressive hearing loss
Apoptosis in cochlear cells	Programmed cell death triggered by oxidative and mitochondrial stress	Loss of inner/outer hair cells and spiral ganglion neurons ® hallmark of ARHL

The insulin-like growth factor 1 (IGF-1) has a vital role in the development of the nervous system. Profound deafness, intellectual disability, and poor growth are the outcomes of a mutation in IGF-1 in humans.⁶⁷ The level of IGF-1 is highest at puberty and adulthood and decreases with age.⁶⁸ The IGF-1 also functions in neuroprotection, as its level is upregulated after brain injury. In a study, it was reported that IFG-1−/− null mice suffered from deafness at all stages, whereas IGF-1+/+ wild-type mice had a degeneration of spiral ganglion and suffered from significant presbycusis with a decrease in the level of IFG-1 with advancing age. So, it is suggested that IGF-1 is essential for the development and maintenance of normal hearing.⁶⁹

Evidences suggest that hearing loss leads to a decrease in social activities, thus social isolation in these persons.⁷⁰ The untreated hearing loss causes less educational attainment and thus less occupational status.⁷¹ Other studies report that females with hearing impairment face a social problem of not being married, whereas males are more likely to get married with hearing loss. However, psychological distress is a common problem both in men and women with hearing loss.⁷² Other effects are also shown in Figure 2. Risk factors and preventive approaches for ARHL have been explained in Table 2.

Table 2: Deep risk factors and preventive approaches for ARHL.
Category	Risk Factor	Mechanism/Contribution to ARHL	Preventive Approach
Genetic factors	Genetic predisposition (e.g., mitochondrial mutations)	Inherited susceptibility to oxidative stress or mitochondrial dysfunction	Genetic screening, personalized medicine
Mitochondrial decline	mtDNA mutations, impaired biogenesis	Reduced energy production in cochlear cells, increased apoptosis	Antioxidant support, mitochondrial protectants (e.g., CoQ10, PQQ)
Oxidative stress	Excess ROS production	Damages cochlear hair cells and neurons	Antioxidants (e.g., vitamins C and E), lifestyle changes
Inflammation	Chronic low-grade inflammation (inflammaging)	Promotes cochlear tissue degeneration	Anti-inflammatory diet, physical activity
Noise exposure	Lifetime occupational or recreational noise	Accelerates cochlear damage and hair cell loss	Use of ear protection, noise regulations
Ototoxic medications	Aminoglycosides, cisplatin, loop diuretics, etc.	Direct toxicity to cochlear structures	Monitoring and limiting ototoxic drug exposure, alternatives when possible
Metabolic disorders	Diabetes, hypertension, dyslipidemia	Impair blood supply and increase oxidative stress in the cochlea	Control of blood glucose, BP, and lipid levels
Nutritional deficiency	Lack of essential vitamins/minerals (B12, folate, Mg, Zn)	Impairs nerve and vascular health	Balanced diet, supplementation as needed
Lifestyle factors	Smoking, alcohol abuse, sedentary lifestyle	Increases oxidative and inflammatory burden	Smoking cessation, moderation in alcohol, regular exercise
Age-related changes	Degeneration of cochlear cells and neurons	Natural decline in cell function and repair capacity	Early monitoring, auditory training, hearing aids as needed
Cognitive decline	Hearing loss and cognitive aging are interconnected	Hearing loss may worsen cognitive decline	Hearing rehabilitation may reduce cognitive burden
Socioeconomic factors	Limited access to hearing health care	Delayed diagnosis and treatment	Public health education, access to screening, and audiology services

Assessment of Hearing Loss

The physician should be vigilant in performing an early diagnosis of speech and language development in neonates, so that hearing loss can be detected at an early stage. The diagnosis includes physical examination of the child, in which assessment is made on the outer and inner ear morphology, facial symmetry and movement, head and jaw size, and their symmetry. Audiologic studies using the auditory brainstem response test give efficient hearing thresholds. Ancillary studies and imaging studies (MRI) are also effective in the early diagnosis of hearing loss. For pediatric hearing loss, laboratory tests are also effective and reliable. Complete blood count, thyroid function test, urinalysis, and autoimmune serologies are performed in this regard. The other mode of assessment includes consultation from an ophthalmologist and genetic testing. For assessment of presbycusis, speech audiometry and pure tone audiometry are effective. The diagnosis of hearing loss is based on the physical and medical history of the patient. The capability for localization of sound is reduced in the patients.⁷³

Prevention and Treatment of ARHL

Altering Behavior

Many environmental/behavioral factors exaggerate the risk of ARHL. Ototoxicity, excessive noise, smoking, and low standards of living contribute to the risk of ARHL. Avoiding all of these factors will ultimately reduce the risk of ARHL. Hygienic living conditions, proper diet, and exercise are likely to preserve the hearing.

Pharmacological Approach

Calcium channel blockers may provide protection against ARHL. The dietary antioxidants may also prove effective against cochlear changes in ARHL.⁶⁵ The redox homeostasis may also provide a web of checks and balances in antioxidant therapy (Wangemann Chap. 3). ROS perform signaling functions at their low concentration. However, the exogenous agents can disturb this balance.⁷⁴ Several drugs are efficient in producing positive results of caloric restrictions. Metformin, 2-deoxyglucose (used for diabetes treatment), and resveratrol⁷⁵ are included in these drugs. The first two drugs have their own potential risks and, therefore, are not recommended in anti-aging therapies. Resveratrol, on the other hand, is efficient in controlling the age-related pathologies by increasing the level of SIRT1, which is a longevity-promoting protein in mammals.

“Preconditioning” is another important phenomenon that provides protection against ARHL. The preconditioning includes noise exposure, heat shock, restraint, and hypoxia, applied in a controlled manner. This preconditioning involves noninjurious “noise-conditioning” and later on injurious “toughening”.⁷⁶ However, the approach is impractical and is not applied clinically. This preconditioning activates some transcription factors, which will produce protective effects against certain diseases, including ARHL.⁷⁷

Restoration of Lost Hearing

Prevention is the best option against ARHL. The restoration of lost cells poses a great challenge. The irreversible changes may occur in other cells due to a decrease in the cell population of the cochlea. For example, the loss of hair cells will ultimately lead to the replacement of the organ of Corti. Cochlear implants and hearing aids, however, may prove efficient in restoring the hearing capability. Cochlear implants are highly recommended as they are helpful in promoting the afferent neuron survival. Gene therapy is another option for restoring hearing, but it requires reprogramming of many cell types.

Use of Hearing Aids

Historically, the primary remediation for hearing loss has been the use of hearing aids. Modern technology has helped to develop advanced hearing devices. The hearing aids that are being used include smartphones, personal sound amplification products, hearing apps, and wireless hearing aids. These devices, however, are not affordable to many individuals. Moreover, there have been many reports that show that in spite of possessing these devices, many people do not use or rely on them. An evidence-graded decision matrix for ARHL management has been explained in Table 3.

Table 3: Evidence-graded decision matrix for arhl management.
Intervention	Level of Evidence (GRADE)	Effectiveness	Target Population	Clinical Recommendation Strength
Hearing aids	High	Improves hearing function, quality of life	Mild-to-moderate sensorineural hearing loss	Strong
Cochlear implants	Moderate to High	Improves speech perception in severe cases	Severe-to-profound hearing loss	Strong
Antioxidant supplementation	Low to Moderate	Some benefit in slowing cochlear damage	Elderly at risk of oxidative stress	Conditional
Auditory rehabilitation (training)	Moderate	Improves communication strategies	Hearing-impaired older adults	Strong
Regular audiologic monitoring	High	Early detection, treatment adjustments	All older adults, especially at risk	Strong
Noise exposure reduction	High	Prevents additional hearing damage	All populations	Strong
Pharmacologic agents (e.g., neuroprotectants, anti-inflammatories)	Low	Experimental, unclear long-term outcomes	Under clinical investigation	Weak (Investigational)
Lifestyle modifications (e.g., exercise, diet)	Moderate	Reduces systemic risks contributing to ARHL	Aging population with comorbidities	Strong
Management of comorbidities (diabetes, hypertension)	High	Indirectly preserves cochlear health	Adults with metabolic or vascular conditions	Strong
Genetic screening/precision therapy	Low to Moderate	Emerging tool, not yet standard	At-risk families, early-onset ARHL	Conditional

Conclusion

It is concluded from the study that hearing loss is a prevalent condition in the world and ARHL is the most common communication disorder in the world. The gene for hearing is located on chromosome 10 in humans. However, many QTLs are involved in controlling the process of hearing and hearing loss. ARHL is the outcome of the process of aging. Damaged DNA or death of the cell will lead to presbycusis. ROS and errors in mitochondrial DNA are other causes of ARHL. The suppression or defect in the genes encoding antioxidant enzymes will exacerbate the process of ARHL. Controlling the process of aging will help slow the onset of ARHL.

References

1. Chen X, Fu YY, Zhang TY. Role of viral infection in sudden hearing loss. J Int Med Res. 2019;47(7):2865–72.
2. Solomon A, Shofoluwe NA, Ahmad H, Isa A, Yunusa SI, Manir HA. Risk factors for sensorineural hearing loss in children and adolescents with sickle cell disease. Iran J Otorhinolaryngol. 2025;37(3):123.
3. Boppana SB, Britt WJ. Synopsis of clinical aspects of human cytomegalovirus disease. In: Reddehase MJ, editor. Cytomegaloviruses: from molecular pathogenesis to intervention. Vol. 2. Poole: Caister Academic Press; 2013. p. 1–25.
4. Bale JF. Cytomegalovirus infections. Semin Pediatr Neurol. 2012;19:101–6.
5. Dahle AJ, Fowler KB, Wright JD, Boppana SB, Britt WJ, Pass RF. Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol. 2000;11:283–90.
6. Schraff SA, Schleiss MR, Brown DK, Meinzen-Derr J, Choi KY, Greinwald JH, et al. Macrophage inflammatory proteins in cytomegalovirus-related inner ear injury. J Otolaryngol Head Neck Surg. 2007;137(4):612–8.
7. Pandey M, Dudeja A, Datta V, Singla B, Saili A. Congenital rubella syndrome. Indian J Pediatr. 2013;80:613–4.
8. Kumarasamy N, Solomon S, Madhivanan P, Ravikumar B, Thyagarajan SP, Yesudian P. Dermatologic manifestations among human immunodeficiency virus patients in south India. Int J Dermatol. 2000;39(3):192–5.
9. Van der Westhuizen Y, Swanepoel DW, Heinze B, Hofmeyr LM. Auditory and otological manifestations in adults with HIV/AIDS. Int J Audiol. 2013;52(1):37–43.
10. Pappas JD, Lim J, Hillman D. Ultrastructural findings in the cochlea of AIDS cases. Am J Otol. 1994;15(4):456–65.
11. Belada A, Köder A, Sungur MA. Did increase of rates of sudden hearing loss during COVID-19?. Konuralp Med J. 2025;17(1):48–51.
12. Senanayake SN. Mumps: a resurgent disease with protean manifestations. Med J Aust. 2008;189(8):456–9.
13. Sturt AS, Dokubo EK, Sint TT. Antiretroviral therapy (ART) for treating HIV infection in ART-eligible pregnant women. Cochrane Database Syst Rev. 2010;(3):CD008440.
14. Nelson DI, Nelson RY, Concha-Barrientos M, Fingerhut M. The global burden of occupational noise-induced hearing loss. Am J Ind Med. 2005;48(6):446–58.
15. Lie A, Skogstad M, Johnsen TS, Engdahl B, Tambs K. The prevalence of notched audiograms in a cross-sectional study of 12,055 railway workers. Ear Hear. 2015;36(3):86–92.
16. Somma G, Pietroiusti A, Magrini A, Coppeta L, Ancona C, Gardi S, Messina M, et al. Extended high-frequency audiometry and noise induced hearing loss in cement workers. Am J Ind Med. 2008;51(6):452–62.
17. Leensen M, Van Duivenbooden J, Dreschler W. A retrospective analysis of noise-induced hearing loss in the Dutch construction industry. Int Arch Occup Environ Health. 2011;84(5):577–90.
18. Bhumika N, Prabhu G, Ferreira A, Kulkarni M. Noise. Induced hearing loss still a problem in shipbuilders: a cross. Sectional study in Goa, India. Ann Med Health Sci Res. 2013;3(1):1–6.
19. Helfer TM, Jordan NN, Lee RB, Pietrusiak P, Cave K, Schairer K. Noise-induced hearing injury and comorbidities among postdeployment US Army soldiers: April 2003–June 2009. Am J Audiol. 2011;20(1):33–41.
20. Orsello CA, Moore JE, Reese C. Sensorineural hearing loss incidence among US military aviators between 1997 and 2011. Aviat Space Environ Med. 2013;84(9):975–9.
21. Muhr P, Månsson B, Hellström PA. A study of hearing changes among military conscripts in the Swedish Army: Estudio de los cambios auditivos en conscriptos de la Armada Sueca. Int J Audiol. 2006;45(4):247–51.
22. Stewart M, Scherer J, Lehman ME. Perceived effects of high frequency hearing loss in a farming population. J Am Acad Audiol. 2003;14(2):100–8.
23. Alter IL, Chern A, Denham MW, Leiderman A, Galatioto J, Jones J, et al. Longitudinal assessment of music enjoyment in hearing aid users based on music listening preferences. Otolaryngol Head Neck Surg. 2025;173(1):80–87.
24. Carlsson P-I, Van Laer L, Borg E, Bondeson M-L, Thys M, Fransen E, et al. The influence of genetic variation in oxidative stress genes on human noise susceptibility. Hear Res. 2005;202:87–96.
25. Gao X, Su Y, Guan L-P, Yuan Y-Y, Huang S-S, Lu Y, et al. Novel compound heterozygous TMC1 mutations associated with autosomal recessive hearing loss in a Chinese family. PLoS one. 2013;8:e63026.
26. Gates GA, Mills JH. Presbycusis. Lancet. 2005;366(9491):1111–20.
27. Cruickshanks KJ, Wiley TL, Tweed TS, Klein BE, Klein R, Mares-Perlman JA, et al. Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin: the epidemiology of hearing loss study. Am J Epidemiol. 1998;148(9):879–86.
28. Hoffman HJ, Dobie RA, Ko C-W, Themann CL, Murphy WJ. Hearing threshold levels at age 70 years (65–74 years) in the unscreened older adult population of the United States, 1959–1962 and 1999–2006. Ear Hear. 2012;33(3):437–40.
29. Agrawal Y, Platz EA, Niparko JK. Risk factors for hearing loss in US adults: data from the National Health and Nutrition Examination Survey, 1999 to 2002. Otol Neurotol. 2009;30(2):139–45.
30. Gates GA, Cobb JL, D’Agostino RB, Wolf PA. The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors. Arch Otolaryngol Head Neck Surg. 1993;119:156–61.
31. Helzner EP, Patel AS, Pratt S, Sutton-Tyrrell K, Cauley JA, Talbott E, et al. Hearing sensitivity in older adults: associations with cardiovascular risk factors in the health, aging and body composition study. J Am Geriatr Soc. 2011;59(6):972–9.
32. Hull RH, Kerschen SR. The influence of cardiovascular health on peripheral and central auditory function in adults: a research review. Am J Audiol. 2010;19(1):9–16.
33. Horikawa C, Kodama S, Tanaka S, Fujihara K, Hirasawa R, Yachi Y, et al. Diabetes and risk of hearing impairment in adults: a meta-analysis. J Clin Endocrinol Metab. 2013;19(1):51–8.
34. Sugimoto S, Teranishi M, Fukunaga Y, Yoshida T, Sugiura S, Uchida Y, et al. Contributing factors to hearing of diabetic patients in an in-hospital education program. Acta Otolaryngol. 2013;133(11):1165–72.
35. Lisowska G, Namyslowski G, Morawski K, Strojek K. Early identification of hearing impairment in patients with type 1 diabetes mellitus. Otol Neurotol. 2001;22(3):316–20.
36. Sachdeva K, Azim S. Sensorineural hearing loss and type II diabetes mellitus. Int J Otorhinolaryngol Head Neck Surg. 2018;4(2):499–507
37. Suresh S, Ramlan S, Somayaji G, Sequeira N. Brainstem auditory responses in type-2 diabetes mellitus. Int J Otorhinolaryngol Head Neck Surg. 2018;4(2):522–5.
38. Marchiori LLdM, Rego Filho EdA, Matsuo T. Hypertension as a factor associated with hearing loss. Rev Brasil Otorrinolaringol. 2006;72(4):533–40.
39. Shargorodsky J, Curhan SG, Curhan GC, Eavey R. Change in prevalence of hearing loss in US adolescents. JAMA. 2010;304(7):772–8.
40. Danhauer JL, Johnson CE, Byrd A, DeGood L, Meuel C, Pecile A, et al. Survey of college students on iPod use and hearing health. J Am Acad Audiol. 2009;20(1):5–27.
41. Widén SO, Erlandsson SI. Self-reported tinnitus and noise sensitivity among adolescents in Sweden. Noise Health. 2004;7(25):29–40.
42. Rawool VW, Colligon-Wayne LA. Auditory lifestyles and beliefs related to hearing loss among college students in the USA. Noise Health. 2008;10:1–10.
43. Smits C, Merkus P, Houtgast T. How we do it: the Dutch functional hearing–screening tests by telephone and internet. Clin Otolaryngol.2006;31(5):436–40.
44. Van Eyken E, Van Camp G, Van Laer L. The complexity of age-related hearing impairment: contributing environmental and genetic factors. Audiol Neurootol. 2007;12(6):345–58.
45. Agrawal Y, Platz EA, Niparko JK. Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey, 1999-2004. Arch Intern Med. 2008;168(14):1522–30.
46. Barrenäs M-L, Lindgren F. The influence of eye colour on susceptibility to TTS in humans. Br J Audiol. 1991;25(5):303–7.
47. Niskar AS, Kieszak SM, Holmes AE, Esteban E, Rubin C, Brody DJ. Estimated prevalence of noise-induced hearing threshold shifts among children 6 to 19 years of age: the Third National Health and Nutrition Examination Survey, 1988–1994, United States. Pediatrics. 2001;108(1):40–3.
48. Harrison R, Nagasawa A, Smith D, Stanton S, Mount R. Reorganization of auditory cortex after neonatal high frequency cochlear hearing loss. Hear Res. 1991;54(1):11–9.
49. Sha S-H, Kanicki A, Dootz G, Talaska AE, Halsey K, Dolan D, et al. Age-related auditory pathology in the CBA/J mouse. Hear Res.2008;243(1–2):87–94.
50. Saitoh Y, Hosokawa M, Shimada A, Watanabe Y, Yasuda N, Murakami Y, et al. Age-related cochlear degeneration in senescence-accelerated mouse. Neurobiol Aging. 1995;16(2):129–36.
51. Abel SM, Giguère C, Consoli A, Papsin BC. The effect of aging on horizontal plane sound localization. J Acoust Soc Am. 2000;108(2):743–52.
52. Erway LC, Willott JF, Archer JR, Harrison DE. Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strains. Hear Res. 1993;65:125–32.
53. Johnson KR, Zheng QY, Erway LC. A major gene affecting age-related hearing loss is common to at least ten inbred strains of mice. Genomics. 2000;70(2):171–80.
54. Jimenez AM, Stagner BB, Martin GK, Lonsbury-Martin BL. Susceptibility of DPOAEs to sound overexposure in inbred mice with AHL. J Assoc Res Otolaryngol. 2001;2(3):233–45.
55. Anderson JM, Van Itallie CM. Physiology and function of the tight junction. Cold Spring Harb Perspect Biol. 2009;1(2):a002584.
56. Kale S, Traenkner D, Goodrich EJ, Ghimire SR, Coate TM, Deans MR. PROX1 controls cellular patterning, innervation and differentiation in the mouse organ of corti. bioRxiv. 2025:2025-04.
57. Drayton M, Noben-Trauth K. Mapping quantitative trait loci for hearing loss in Black Swiss mice. Hear Res. 2006;212(1):128–39.
58. Nagtegaal A, Spijker S, Crins T, Borst J. A novel QTL underlying early-onset, low-frequency hearing loss in BXD recombinant inbred strain. Genes Brain Behav. 2012;11(8):911–20.
59. Noben-Trauth K, Zheng QY, Johnson KR. Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss. Nat Genet. 2003;35(1):21–3.
60. Johnson KR, Zheng QY, Noben-Trauth K. Strain background effects and genetic modifiers of hearing in mice. Brain Res. 2006;1091(1):79–88.
61. Geesaman BJ. Genetics of aging: implications for drug discovery and development. Am J Clin Nutr. 2006;83(2):466–9.
62. Harper JM, Salmon AB, Chang Y, Bonkowski M, Bartke A, Miller RA. Stress resistance and aging: influence of genes and nutrition. Mech Ageing Dev. 2006;127(8):687–94.
63. Zglinicki TV, Martin-Ruiz C. Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med. 2005;5(2):197–203.
64. Leutner S, Eckert A, Müller W. ROS generation, lipid peroxidation and antioxidant enzyme activities in the aging brain. J Neural Transm. 2001;108:955–67.
65. Seidman MD. Effects of dietary restriction and antioxidants on presbyacusis. Laryngoscope. 2000;110(5):727–38.
66. Lang H, Schulte BA, Zhou D, Smythe N, Spicer SS, Schmiedt RA. Nuclear factor κB deficiency is associated with auditory nerve degeneration and increased noise-induced hearing loss. J Neurosci. 2006;26(13):3541–50.
67. Walenkamp M, Wit J. Genetic disorders in the GH–IGF-I axis in mouse and man. Eur J Endocrinol. 2007;157:15–26.
68. Montserrat N, Gómez-Requeni P, Bellini G, Capilla E, Pérez-Sánchez J, Navarro I, et al. Distinct role of insulin and IGF-I and its receptors in white skeletal muscle during the compensatory growth of gilthead sea bream (Sparus aurata). Aquaculture. 2007;267:188–98.
69. Riquelme R, Cediel R, Contreras J, Rodríguez-de La Rosa L, Murillo-Cuesta S, Hernandez C, et al. A comparative study of age-related hearing loss in wild type and insulin-like growth factor I deficient mice. Front Neuroanat. 2010;4:27.
70. Arlinger S. Negative consequences of uncorrected hearing loss-a review. Int J Audiol. 2003;42:17–20.
71. Schley S, Walter GG, Weathers RR, Hemmeter J, Hennessey JC, Burkhauser RV. Effect of postsecondary education on the economic status of persons who are deaf or hard of hearing. J Deaf Stud Deaf Educ. 2011;16(4):524–36.
72. Kobayashi Y, Tamiya N, Moriyama Y, Nishi A. Triple difficulties in Japanese women with hearing loss: marriage, smoking, and mental health issues. PLoS One. 2015;10(2):e0116648.
73. Kim TS, Chung JW. Evaluation of age-related hearing loss. Korean J Audiol. 2013;17(2):50–3.
74. Ohlemiller KK. Oxidative cochlear injury and the limitations of antioxidant therapy. Semin Hear. 2003;24(2):123–34.
75. Sinclair DA. Toward a unified theory of caloric restriction and longevity. Mech Ageing Dev. 2005;126(9):987–1002.
76. Ma Q, Wang Q, Zhu Z, Zhou Q, Wang Z, Qian M, et al. Single-cell sequencing reveals circadian sensitivity of noise-induced hearing loss mediated by macrophage-driven NLRP3 inflammasome activation. Neurosci Bull. 2025;3:1–9.
77. Gagnon PM, Simmons DD, Bao J, Lei D, Ortmann AJ, Ohlemiller KK. Temporal and genetic influences on protection against noise-induced hearing loss by hypoxic preconditioning in mice. Hear Res. 2007;226:79–91.

Cite this article as:
Qadir MI and Gillani M. Age-Related Hearing Loss: A Review of a Hot Topic in Audiology. Premier Journal of Genetics 2025;3:100004

Export to EndNote Export to Mendeley